References on Thyroid Hormone Usefulness

I pre­sent to you a near-exhaustive list of refe­ren­ces on the use­ful­ness of thy­roid hor­mo­nes in diverse age-related disea­ses. These come out of the Hor­mone Hand­book by Thierry Her­toghe, MD (Inter­na­tio­nal Medi­cal Books) and are pre­sen­ted here with per­mis­sion by Her­toghe. Dr. Her­toghe of Bel­gium is one of Europe’s lea­ding pro­fes­sio­nal advo­ca­tes of anti-aging medicine.

Senes­cence (the aging pro­cess in mature indi­vi­duals) is asso­cia­ted with a dec­line of the thy­roid axis

Reduc­tions of TSH, T3 and T4 with senescence

1. Wie­ner R, Uti­ger RD, Lew R, Emer­son CH. Age, sex, and serum thy­ro­tro­pin con­cen­tra­tions in pri­mary hypothy­roi­dism. Acta Endoc­ri­nol (Copenh). 1991 Apr;124(4):364 – 9
2. Ber­mu­dez F, Surks MI, Oppenhei­mer JH. High inci­dence of dec­rea­sed serum triio­dothy­ro­nine con­cen­tra­tion in patients with nonthy­roi­dal disease. J Clin Endoc­ri­nol Metab. 1975 Jul;41(1):27 – 40
3. Hesch RD, Gatz J, Jupp­ner H, Stubbe P. TBG-dependency of age rela­ted varia­tions of thy­ro­xine and triio­dothy­ro­nine. Horm Metab Res. 1977 Mar;9(2):141 – 6
4. Herr­mann J, Hei­nen E, Kroll HJ, Rudorff KH, Krus­kem­per HL. Thy­roid func­tion and thy­roid hor­mone meta­bo­lism in elderly peo­ple. Low T3-syndrome in old age? Klin Wochenschr. 1981 Apr 1;59(7):315 – 23
5. Djord­je­vic MZ, Paun­ko­vic ND, Djordjevic-Lalosevic VB, Paun­ko­vic Dz S. The effect of age on in vitro thy­roid func­tion tests in adult patients on a chro­nic hemo­dialy­sis pro­gram. Srp Arh Celok Lek. 1990 Jul-Aug;118(7 – 8):291 – 3
6. Spaul­ding SW. Age and the thy­roid. Endoc­ri­nol Metab Clin North Am. 1987 Dec;16(4):1013 – 25
14. Smeu­lers J, Vis­ser TJ, Bur­ger AK, Doc­ter R, Hen­ne­mann G. Dec­rea­sed triio­dothy­ro­nine (T3) pro­duc­tion in cons­tant reverse T3 pro­duc­tion in advan­ced age. Ned Tijdschr Geneeskd. 1979 Jan 6;123(1):12 – 5 

Dec­rease of the meta­bo­lic clea­rance of thy­roid hor­mo­nes with age

7. Gre­ger­man RI, Gaff­ney GW, Shock NW, Crow­der SE. Thy­ro­xine tur­no­ver in euthy­roid man with spe­cial refe­rence to chan­ges with age. J Clin Invest. 1962 Nov;41:2065 – 74
8. Katzeff HL. Inc­rea­sing age impairs the thy­roid hor­mone res­ponse to over­fee­ding. Proc Soc Exp Biol Med. 1990 Jul;194(3):198 – 203

Reduc­tion of the amount of thy­roid hor­mone (cellu­lar) recep­tors with age

9. Kvetny J. Nuc­lear thy­ro­xine and triio­dothy­ro­nine bin­ding in mono­nuc­lear cells in depen­dence of age. Horm Metab Res. 1985 Jan;17(1):35 – 8

Alte­ra­tion of the cir­ca­dian cycle of serum TSH with age: redu­ced ampli­tude and phase advance

10. Greens­pan SL, Kli­banski A, Rowe JW, Elahi D. Age-related alte­ra­tions in pul­sa­tile sec­re­tion of TSH: role of dopa­mi­ner­gic regu­la­tion. Am J Phy­siol. 1991 Mar;260(3 Pt 1):E486-91
11. Barreca T, Fran­ceschini R, Mes­sina V, Bot­taro L, Rolandi E. 24-hour thyroid-stimulating hor­mone sec­re­tory pat­tern in elderly men. Geron­to­logy. 1985;31(2):119 – 23

Thy­roid hor­mo­nes may oppose and thy­roid hor­mo­nes defi­ciency may trig­ger seve­ral mecha­nisms of senescence 

Exces­sive free radi­cal for­ma­tion: thy­roid hor­mo­nes sti­mu­late antio­xi­dant activity

12. Anti­penko AYe, Anti­penko YN. Thy­roid hor­mo­nes and regu­la­tion of cell relia­bi­lity sys­tems. Adv Enzyme Regul. 1994;34:173 – 98
13. Tseng YL, Latham KR. Iodothy­ro­ni­nes: oxi­da­tive deio­di­na­tion by hemo­glo­bin and inhi­bi­tion of lipid pero­xi­da­tion. Lipids. 1984 Feb;19(2):96 – 102
14. Bozhko AP, Goro­dets­kaia IV. The role of thy­roid hor­mo­nes in pre­ven­tion of disor­ders of myo­car­dial con­trac­tile func­tion and antio­xi­dant acti­vity during heat stress. Ross Fiziol Zh Im I M Seche­nova. 1998 Mar;84(3):226 – 32
15. Faure P, Oziol L, Artur Y, Cho­mard P. Thy­roid hor­mone (T3) and its ace­tic deri­va­tive (TA3) pro­tect low-density lipo­pro­teins from oxi­da­tion by dif­fe­rent mecha­nisms. Biochi­mie. 2004 Jun;86(6):411 – 8
16. Brzezinska-Slebodzinska E. Influence of hypothy­roi­dism on lipid pero­xi­da­tion, eryth­rocyte resis­tance and antio­xi­dant plasma pro­per­ties in rab­bits. Acta Vet Hung. 2003;51(3):343 – 51
17. Oziol L, Faure P, Ber­trand N, Cho­mard P. Inhi­bi­tion of in vitro macrophage-induced low den­sity lipo­pro­tein oxi­da­tion by thy­roid com­pounds. J Endoc­ri­nol. 2003 Apr;177(1):137 – 46

Imba­lan­ced apop­to­sis: TSH inhi­bits unde­si­ra­ble apotosis

18. Feld­kamp J, Pascher E, Per­niok A, Scher­baum WA. Fas-Mediated apop­to­sis is inhi­bi­ted by TSH and iodine in mode­rate con­cen­tra­tions in pri­mary human thy­rocy­tes in vitro. Horm Metab Res. 1999 Jun;31(6):355 – 8. 

Mala­borp­tion of impor­tant nutrients: thy­roid hor­mo­nes improve mac­ro­nu­trient uptake

19.Misra GC, Bose SL Samal AK. Malab­sorp­tion in thy­roid dys­func­tions. J Indian Med Assoc. 1991 Jul;89(7):195 – 7

Fai­lure of repair sys­tems: thy­roid hor­mo­nes reduce damage and acce­le­rate repair

20. Pal­mer KC, Mari F, Malian MS. Cadmium-induced acute lung injury: com­pro­mi­sed repair res­ponse follo­wing thy­roi­dec­tomy. Envi­ron Res. 1986 Dec;41(2):568 – 84
21. Safer JD, Craw­ford TM, Holick MF. A role for thy­roid hor­mone in wound hea­ling through kera­tin gene expres­sion. Endoc­ri­no­logy. 2004 May;145(5):2357 – 61

Immune defi­ciency: sti­mu­la­tes the immune system

Low thy­roid hor­mone levels are asso­cia­ted with immune deficiency

22. Kmiec Z, Mys­liwska J, Rachon D, Kot­larz G, Sworc­zak K, Mys­liwski A. Natu­ral killer acti­vity and thy­roid hor­mone levels in young and elderly per­sons. Geron­to­logy. 2001 Sep-Oct;47(5):282 – 8
23. Mariani E, Rava­glia G, Forti P, Meneghetti A, Tarozzi A, Maioli F, Boschi F, Pra­te­lli L, Piz­zo­fe­rrato A, Piras F, Facchini A. Vita­min D, thy­roid hor­mo­nes and muscle mass influence natu­ral killer (NK) innate immu­nity in healthy nona­ge­na­rians and cen­te­na­rians. Clin Exp Immu­nol. 1999 Apr;116(1):19 – 27
24. Basso A, Pian­ta­ne­lli L, Ros­so­lini G, Piloni S, Vitali C, Masera N. Role of triio­dothy­ro­nine in down-regulation and reco­very of lymphocyte beta-adrenoceptors in thy­roi­dec­to­mi­zed patients. J Clin Endoc­ri­nol Metab. 1991 Dec;73(6):1340 – 4
25. Chow CC, Mak TW, Chan CH, Cckram CS. Euthy­roid sick syn­drome in pul­mo­nary tuber­cu­lo­sis before and after treat­ment. Ann Clin Biochem. 1995 Jul; 32 (Pt 4): 385 – 91

Thy­roid treat­ment impro­ves the immune defences 

26. Pad­berg S, Heller K, Usa­del KH, Schumm-Draeger PM. One-year prophy­lac­tic treat­ment of euthy­roid Hashimoto’s thy­roi­di­tis patients with levothy­ro­xine: is there a bene­fit? Thy­roid. 2001 Mar;11(3):249 – 55
27. Aksoy DY, Keri­mo­glu U, Okur H, Can­pi­nar H, Karaa­gao­glu E, Yet­gin S, Kansu E, Gedik O. Effects of prophy­lac­tic thy­roid hor­mone repla­ce­ment in euthy­roid Hashimoto’s thy­roi­di­tis. Endocr J. 2005 Jun;52(3):337 – 43
28. Bloehr H, Bre­gen­gaard C, Povl­sen JV. Triio­dothy­ro­nine sti­mu­la­tes growth of periphe­ral blood mono­nuc­lear cells in serum-free cul­tu­res in ure­mic patients. Am J Neph­rol. 1992;12(3):148 – 54
Paa­vo­nen T. Enhan­ce­ment of human B lymphocyte dif­fe­ren­tia­tion in vitro by thy­roid hor­mone. Scand J Immu­nol. 1982 Feb;15(2):211 – 5
29. Botella-Carretero JI, Pra­dos A, Man­zano L, Mon­tero MT, Esc­ri­bano L, Sancho J, Escobar-Morreale HF. The effects of thy­roid hor­mo­nes on cir­cu­la­ting mar­kers of cell-mediated immune res­ponse, as stu­died in patients with dif­fe­ren­tia­ted thy­roid car­ci­noma before and during thy­ro­xine with­dra­wal. Eur J Endoc­ri­nol. 2005 Aug;153(2):223 – 30
30. Balazs C, Leo­vey A, Szabo M, Bako G. Sti­mu­la­ting effect of triio­dothy­ro­nine on cell-mediated immu­nity. Eur J Clin Phar­ma­col. 1980 Jan;17(1):19 – 23
31. Fabris N, Mocche­giani E, Mariotti S, Pacini F, Pinchera A. Thy­roid func­tion modu­la­tes thy­mic endoc­rine acti­vity. J Clin Endoc­ri­nol Metab. 1986 Mar;62(3):474 – 8
32. Dorsh­kind K, Hor­se­man ND. The roles of pro­lac­tin, growth hor­mone, insulin-like growth factor-I, and thy­roid hor­mo­nes in lymphocyte deve­lop­ment and func­tion: insights from gene­tic models of hor­mone and hor­mone recep­tor defi­ciency. Endocr Rev. 2000 Jun;21(3):292 – 312
33. Kvetny J, Matzen LE. Thy­roid hor­mone indu­ced oxy­gen con­sump­tion and glucose-uptake in human mono­nuc­lear cells. Thy­roi­do­logy. 1989 Apr;1(1):5 – 9
34. McCor­mack PD, Tho­mas J, Malik M, Staschen CM. Cold stress, reverse T3 and lymphocyte func­tion. Alaska Med. 1998 Jul-Sep;40(3):55 – 62

Limits to healthy cell pro­li­fe­ra­tion: sti­mu­la­tes fibro­blast pro­li­fe­ra­tion and differentiation

35. Ahsan MK, Urano Y, Kato S, Oura H, Arase S. Immu­nohis­toche­mi­cal loca­li­za­tion of thy­roid hor­mone nuc­lear recep­tors in human hair follic­les and in vitro effect of L-triiodothyronine on cul­tu­red cells of hair follic­les and skin. J Med Invest. 1998 Feb;44(3 – 4):179 – 84

Poor gene poly­morphisms: poor thy­roid gene poly­morphisms may inc­rease the risk of age-related disea­ses, and thy­roid dys­func­tion may inc­rease the risk of phe­noty­pic expres­sion of other unfa­vou­ra­ble gene polymorphisms

36. Hus­tad S, Nedrebo BG, Ueland PM, Sch­neede J, Voll­set SE, Ulvik A, Lien EA. Phe­noty­pic expres­sion of the methy­le­ne­te­trahy­dro­fo­late reduc­tase 677C – >T poly­morphism and fla­vin cofac­tor avai­la­bi­lity in thy­roid dys­func­tion. Am J Clin Nutr. 2004 Oct;80(4):1050 – 7
37. Silva JM, Domin­guez G, Gonzalez-Sancho JM, Gar­cia JM, Silva J, Garcia-Andrade C, Nava­rro A, Munoz A, Boni­lla F. Expres­sion of thy­roid hor­mone receptor/erbA genes is alte­red in human breast can­cer. Onco­gene. 2002 Jun 20;21(27):4307 – 16

Thy­roid hor­mo­nes and psychic well-being

Lower qua­lity of life and fati­gue: the asso­cia­tion with lower thy­roid hor­mone levels

38. Kong WM, Sheikh MH, Lumb PJ, Naou­mova RP, Freed­man DB, Crook M, Dore CJ, Finer N, Naou­mova P. A 6-month ran­do­mi­zed trial of thy­ro­xine treat­ment in women with mild subc­li­ni­cal hypothy­roi­dism. Am J Med. 2002 Apr 1;112(5):348 – 54
39. Gui­ma­raes V, DeGroot LJ. Mode­rate hypothy­roi­dism in pre­pa­ra­tion for whole body 131I scin­tis­cans and thy­ro­glo­bu­lin tes­ting. Thy­roid. 1996 Apr;6(2):69 – 73
40. Heit­man B, Iri­zarry A. Hypothy­roi­dism: com­mon com­plaints, per­ple­xing diag­no­sis. Nurse Pract. 1995 Mar;20(3):54 – 60
41. Dou­cet J, Tri­va­lle C, Chas­sagne P, Perol MB, Vui­ller­met P, Manchon ND, Menard,JF, Ber­coff E. Does age play a role in cli­ni­cal pre­sen­ta­tion of hypothy­roi­dism? J Am Geriatr Soc. 1994 Sep;42(9):984 – 6
42. De Lorenzo F, Xiao H, Mukher­jee M, Har­cup J, Sulei­man S, Kad­ziola Z, Kak­kar VV. Chro­nic fati­gue syn­drome: phy­si­cal and car­dio­vas­cu­lar decon­di­tio­ning. QJM. 1998 Jul;91(7):475 – 81

Lower qua­lity of life and fati­gue: the impro­ve­ment with thy­roid treatment

43. Dzu­rec LC. Expe­rien­ces of fati­gue and depres­sion before and after low-dose L-thyroxine sup­ple­men­ta­tion in essen­tially euthy­roid indi­vi­duals. Res Nurs Health. 1997 Oct;20(5):389 – 98
44. Bune­vi­cius R, Kaza­na­vi­cius G, Zalin­ke­vi­cius R, Prange AJ Jr. Effects of thy­ro­xine as com­pa­red with thy­ro­xine plus triio­dothy­ro­nine in patients with hypothy­roi­dism. N Engl J Med. 1999 Feb 11;340(6):424 – 9
45. Her­toghe T, Lo Cas­cio A., Her­toghe J. Con­si­de­ra­ble impro­ve­ment of hypothy­roid symp­toms with two com­bi­ned T3-T4 medi­ca­tion in patients still symp­to­ma­tic with thy­ro­xine treat­ment alone. Anti-Aging Medi­cine, Ed. Ger­man Society of Anti-Aging Medicine-Verlag 2003– 2004; 32 – 43
46. Hashi­zume K. Sup­ple­ment with tar­get hor­mone in aged patients with endoc­rine dys­func­tion: thy­roid hor­mone repla­ce­ment the­rapy. Nip­pon Ronen Igak­kai Zasshi. 2000 Nov;37(11):870 – 2.
47. Sur­kov SI, Naa­rov AN, Kotova GA, Arte­mova AM. The effi­cacy of repla­ce­ment the­rapy with L-thyroxine in mani­fest and latent forms of hypothy­roi­dism. Probl Endo­kri­nol (Mosk). 1990 Sep-Oct;36(5):14 – 8. 

Depres­sion: the asso­cia­tion with lower thy­roid hor­mone levels

48. Pop VJ, Maar­tens LH, Leu­sink G, van Son MJ, Knott­ne­rus AA, Ward AM, Met­calfe R, Weet­man AP. Are autoim­mune thy­roid dys­func­tion and depres­sion rela­ted? J Clin Endoc­ri­nol Metab. 1998 Sep;83(9):3194 – 7
49. Hag­gerty JJ Jr, Stern RA, Mason GA, Beck­with J, Morey CE, Prange AJ Jr. Subc­li­ni­cal hypothy­roi­dism: a modi­fia­ble risk fac­tor for depres­sion? Am J Psychiatry. 1993 Mar;150(3):508 – 10
50. Gold MS, Pot­tash AL, Extein I. “Symp­tom­less” autoim­mune thy­roi­di­tis in depres­sion. Psychiatry Res. 1982 Jun;6(3):261 – 9
51. O’Shanick GJ, Ellin­wood EH Jr. Per­sis­tent ele­va­tion of thyroid-stimulating hor­mone in women with bipo­lar affec­tive disor­der. Am J Psychiatry. 1982 Apr;139(4):513 – 4
52. How­land RH. Thy­roid dys­func­tion in refrac­tory depres­sion: impli­ca­tions for pathophy­sio­logy and treat­ment. J Clin Psychiatry. 1993 Feb;54(2):47 – 54
53. Kir­ke­gaard C, Nor­lem N, Lau­rid­sen UB, Bjo­rum N, Chris­tian­sen C. Pro­ti­re­lin sti­mu­la­tion test and thy­roid func­tion during treat­ment of depres­sion. Arch Gen Psychiatry. 1975 Sep;32(9):1115 – 8
54. Bauer MS, Why­brow PC, Wino­kur A. Rapid cyc­ling bipo­lar affec­tive disor­der. I. Asso­cia­tion with grade I hypothy­roi­dism. Arch Gen Psychiatry. 1990 May;47(5):427 – 32
55. Hag­gerty JJ Jr, Evans DL, Gol­den RN, Peder­sen CA, Simon JS, Neme­roff CB. The pre­sence of antithy­roid anti­bo­dies in patients with affec­tive and nonaf­fec­tive psychia­tric disor­ders. Biol Psychiatry. 1990 Jan 1;27(1):51 – 60
56. Cole DP, Thase ME, Mallin­ger AG, Soa­res JC, Luther JF, Kup­fer DJ, Frank E. Slo­wer treat­ment res­ponse in bipo­lar depres­sion pre­dic­ted by lower pre-treatment thy­roid func­tion. Am J Psychiatry. 2002 Jan;159(1):116 – 21
57. Joffe RT, Marriott M. Thy­roid hor­mone levels and recu­rrence of major depres­sion. Am J Psychiatry. 2000 Oct;157(10):1689 – 91 (time to recu­rrence of major depres­sion was inver­sely rela­ted to T3 levels but not to T4 levels) 

Depres­sion: the impro­ve­ment with thy­roid treatment

58. Bauer MS, Why­brow PC. Rapid cyc­ling bipo­lar affec­tive disor­der. II. Treat­ment of refrac­tory rapid cyc­ling with high-dose levothy­ro­xine: a pre­li­mi­nary study. Arch Gen Psychiatry. 1990 May;47(5):435 – 40
59. Affle­lou S, Auria­combe M, Caze­nave M, Char­tres JP, Tig­nol J. Admi­nis­tra­tion of high dose levothy­ro­xine in treat­ment of rapid cyc­ling bipo­lar disor­ders. Review of the lite­ra­ture and ini­tial the­ra­peu­tic appli­ca­tion apro­pos of 6 cases. Encephale. 1997 May-Jun;23(3):209 – 17
60. Bauer M, Baur H, Bergho­fer A, Strohle A, Hell­weg R, Muller-Oerlinghausen B, Baum­gart­ner A. Effects of supraphy­sio­lo­gi­cal thy­ro­xine admi­nis­tra­tion in healthy con­trols and patients with depres­sive disor­ders. J Affect Disord. 2002 Apr;68(2 – 3):285 – 94
61. Sch­warcz G, Hala­ris A, Bax­ter L, Esco­bar J, Thomp­son M, Young M. Nor­mal thy­roid func­tion in desi­pra­mine non­res­pon­ders con­ver­ted to res­pon­ders by the addi­tion of L-triiodothyronine. Am J Psychiatry. 1984 Dec;141(12):1614 – 6
62. Prange AJ Jr. Novel uses of thy­roid hor­mo­nes in patients with affec­tive disor­ders. Thy­roid. 1996 Oct;6(5):537 – 43
63. Bir­kenha­ger TK, Vegt M, Nolen WA. An open study of triio­dothy­ro­nine aug­men­ta­tion of tricyc­lic anti­de­pres­sants in inpa­tients with refrac­tory depres­sion. Phar­ma­copsychiatry. 1997 Jan;30(1):23 – 6
64. Joffe RT, Sin­ger W, Levitt AJ, Mac­Do­nald C. A placebo-controlled com­pa­ri­son of lithium and triio­dothy­ro­nine aug­men­ta­tion of tricyc­lic anti­de­pres­sants in uni­po­lar refrac­tory depres­sion. Arch Gen Psychiatry. 1993 May;50(5):387 – 93
65. Altshu­ler LL, Bauer M, Frye MA, Git­lin MJ, Mintz J, Szuba MP, Leight KL, Why­brow PC. Does thy­roid sup­ple­men­ta­tion acce­le­rate tricyc­lic anti­de­pres­sant res­ponse? A review and meta-analysis of the lite­ra­ture. Am J Psychiatry. 2001 Oct;158(10):1617 – 22

Anxiety: the asso­cia­tion with lower thy­roid hor­mone levels

66. Kikuchi M, Komuro R, Oka H, Kidani T, Hanaoka A, Koshino Y. Rela­tionship bet­ween anxiety and thy­roid func­tion in patients with panic disor­der. Prog Neu­ropsychophar­ma­col Biol Psychiatry. 2005 Jan;29(1):77 – 81
67. Bauer M, Priebe S, Kur­ten I, Graf KJ, Baum­gart­ner A. Psycho­lo­gi­cal and endoc­rine abnor­ma­li­ties in refu­gees from East Ger­many: Part I. Pro­lon­ged stress, psycho­patho­logy, and hypothalamic-pituitary-thyroid axis acti­vity. Psychiatry Res. 1994 Jan;51(1):61 – 73
68. Magliozzi JR, Mad­dock RJ, Gold AS, Gie­tzen DW. Rela­tionships bet­ween thy­roid indi­ces and symp­toms of anxiety in depres­sed out­pa­tients Ann Clin Psychiatry. 1993 Jun;5(2):111 – 6
69 Sait Gonen M, Kisa­kol G, Savas Cilli A, Dik­bas O, Gun­gor K, Inal A, Kaya A. Assess­ment of anxiety in subc­li­ni­cal thy­roid disor­ders. Endocr J. 2004 Jun;51(3):311 – 5
70. Larisch R, Kley K, Niko­laus S, Sitte W, Franz M, Hau­tzel H, Tress W, Muller HW.. Depres­sion and anxiety in dif­fe­rent thy­roid func­tion sta­tes. Horm Metab Res. 2004 Sep;36(9):650 – 3
71. Cons­tant EL, Adam S, Seron X, Bru­yer R, Seghers A, Dau­me­rie C. Anxiety and depres­sion, atten­tion, and exe­cu­tive func­tions in hypothy­roi­dism. J Int Neu­ropsychol Soc. 2005 Sep;11(5):535 – 44

Anxiety: the impro­ve­ment with thy­roid treatment

72. Sara­va­nan P, Sim­mons DJ, Green­wood R, Peters TJ, Dayan CM. Par­tial subs­ti­tu­tion of thy­ro­xine (T4) with tri-iodothyronine in patients on T4 repla­ce­ment the­rapy: results of a large community-based ran­do­mi­zed con­tro­lled trial. J Clin Endoc­ri­nol Metab. 2005 Feb;90(2):805 – 12
73. Venero C, Guadano-Ferraz A, Herrero AI, Nords­trom K, Man­zano J, de Esco­bar GM, Ber­nal J, Venns­trom B. Anxiety, memory impair­ment, and loco­mo­tor dys­func­tion cau­sed by a mutant thy­roid hor­mone recep­tor alpha1 can be ame­lio­ra­ted by T3 treat­ment. Genes Dev. 2005 Sep 15;19(18):2152 – 63

Memory loss and Alzheimer’s disease: the asso­cia­tion with lower thy­roid hor­mone levels

74. Naka­nishi T. Con­si­de­ra­tion on serum triio­dothy­ro­nine (T3), thy­ro­xine (T4) con­cen­tra­tion and T3/T4 ratio in the patients of senile demen­tia — is it pos­si­ble to pre­vent cerebro-vascular demen­tia? Igaku Kenkyu. 1990 Feb;60(1):18 – 25
75. Ichi­ban­gase A, Nishi­kawa M, Iwa­saka T, Koba­yashi T, Inada M. Rela­tion bet­ween thy­roid and car­diac func­tions and the geria­tric rating scale. Acta Neu­rol Scand. 1990 Jun;81(6):491 – 8
76. Molchan SE, Law­lor BA, Hill JL, Mellow AM, Davis CL, Mar­ti­nez R, Sun­der­land T. The TRH sti­mu­la­tion test in Alzheimer’s disease and major depres­sion: rela­tionship to cli­ni­cal and CSF mea­su­res. Biol Psychiatry. 1991 Sep 15;30(6):567 – 76
77. Bur­meis­ter LA, Gan­guli M, Dodge HH, Toc­zek T, DeKosky ST, Nebes RD. Hypothy­roi­dism and cog­ni­tion: pre­li­mi­nary evi­dence for a spe­ci­fic defect in memory. Thy­roid. 2001 Dec;11(12):1177 – 85
78. Mon­zani F, Pru­neti CA, De Negri F, Simon­cini M, Neri S, Di Bello V, Baracchini Mura­to­rio G, Baschieri L. Prec­li­ni­cal hypothy­roi­dism: early invol­ve­ment of memory func­tion, beha­viou­ral res­pon­si­ve­ness and myo­car­dial con­trac­ti­lity. Minerva Endoc­ri­nol. 1991 Jul-Sep;16(3):113 – 8
Isti­tuto di Cli­nica Medica II, Uni­ver­sita di Pisa.
Bal­dini IM, Vita A, Maura MC, Amo­dei V, Carrisi M, Bra­vin S, Can­ta­la­messa L. Psycho­patho­lo­gi­cal and cog­ni­tive fea­tu­res in subc­li­ni­cal hypothy­roi­dism. Prog Neu­ropsychophar­ma­col Biol Psychiatry. 1997 Aug;21(6):925 – 35
Gan­guli M, Bur­meis­ter LA, Sea­berg EC, Belle S, DeKosky ST. Asso­cia­tion bet­ween demen­tia and ele­va­ted TSH: a community-based study. Biol Psychiatry. 1996 Oct 15;40(8):714 – 25

Memory loss and Alzheimer’s disease: the impro­ve­ment with thy­roid treatment

79. Mon­zon Mon­gui­lod MJ, Perez Lopez-Fraile I. Subc­li­ni­cal hypothy­roi­dism as a cause of rever­si­ble cog­ni­tive dete­rio­ra­tion. Neu­ro­lo­gia. 1996 Nov;11(9):353 – 6
80. Kinuya S, Michi­gishi T, Tonami N, Abu­rano T, Tsuji S, Hashi­moto T. Rever­si­ble cere­bral hypo­per­fu­sion obser­ved with Tc-99m HMPAO SPECT in rever­si­ble demen­tia cau­sed by hypothy­roi­dism. Clin Nucl Med. 1999 Sep;24(9):666 – 8
Mon­zani F, Del Gue­rra P, Carac­cio N, Pru­neti CA, Pucci E, Luisi M, Baschieri L. Subc­li­ni­cal hypothy­roi­dism: neu­ro­beha­vio­ral fea­tu­res and bene­fi­cial effect of L-thyroxine treat­ment. Clin Inves­tig. 1993 May;71(5):367 – 71
Bal­dini IM, Vita A, Maura MC, Amo­dei V, Carrisi M, Bra­vin S, Can­ta­la­messa L. Psycho­patho­lo­gi­cal and cog­ni­tive fea­tu­res in subc­li­ni­cal hypothy­roi­dism. Prog Neu­ropsychophar­ma­col Biol Psychiatry. 1997 Aug;21(6):925 – 35

Sleep disor­ders: the impro­ve­ment with thy­roid treatment

81. Ruiz-Primo E, Jurado JL, Solis H, Mais­te­rrena JA, Fernandez-Guardiola A, Val­verde C. Poly­som­no­graphic effects of thy­roid hor­mo­nes pri­mary myxe­dema. Elec­troen­cepha­logr Clin Neu­rophy­siol. 1982 May;53(5):559 – 64
82. Orr WC, Males JL, Imes NK. Myxe­dema and obs­truc­tive sleep apnea. Am J Med. 1981 May;70(5):1061 – 6
83. Raja­go­pal KR, Abbrecht PH, Der­de­rian SS, Pic­kett C, Hofeldt F, Tellis CJ, Zwi­llich CW. Obs­truc­tive sleep apnea in hypothy­roi­dism. Ann Intern Med. 1984 Oct;101(4):491 – 4

Fer­ti­lity:
Infer­ti­lity: the asso­cia­tion with lower thy­roid hor­mone levels

Bis­pink L, Brandle W, Lind­ner C, Bet­ten­dorf G. Prec­li­ni­cal hypothy­roi­dism and disor­ders of ova­rian func­tion. Geburtshilfe Frauenheilkd. 1989 Oct;49(10):881 – 8

Thy­roid hor­mo­nes and age-related diseases

Hypercho­les­te­ro­le­mia: the asso­cia­tion with lower thy­roid hor­mone levels

Elder J, McLe­lland A, O’Reilly DS, Pac­kard CJ, Series JJ, Shepherd J. The rela­tionship bet­ween serum cho­les­te­rol and serum thy­ro­tro­pin, thy­ro­xine and tri-iodothyronine con­cen­tra­tions in sus­pec­ted hypothy­roi­dism. Ann Clin Biochem. 1990 Mar;27 ( Pt 2):110 – 3
Sun­da­ram V, Hanna AN, Koneru L, New­man HA, Falko JM. Both hypothy­roi­dism and hyperthy­roi­dism enhance low den­sity lipo­pro­tein oxi­da­tion. J Clin Endoc­ri­nol Metab. 1997 Oct;82(10):3421 – 4

Hypercho­les­te­ro­le­mia: the impro­ve­ment with thy­roid treatment

Wise­man SA, Car­ter G, Alagh­band Zadeh J, Fow­ler PB, Greenhalgh RM. Can thy­ro­xine halt the pro­gres­sion of periphe­ral arte­rial disease? Eur J Vasc Surg. 1989 Feb;3(1):85 – 7
Franklyn JA, Day­kin J, Bet­te­ridge J, Hughes EA, Hol­der R, Jones SR, Shep­pard MC. Thy­ro­xine repla­ce­ment the­rapy and cir­cu­la­ting lipid con­cen­tra­tions. Clin Endoc­ri­nol (Oxf). 1993 May;38(5):453 – 9
Selen­kow HA, Wool MS. A new synthe­tic hor­mone com­bi­na­tion for cli­ni­cal the­rapy. Ann Int Med. 1967 July, 67 (1): 90 – 9
Alley RA, Danowski TS, Rob­bins TJ, Weir TF, Sabeh G, Moses CL. Indi­ces during admi­nis­tra­tion of T4 and T3 to euthy­roid adults. Meta­bo­lism. 1968 Feb;17(2):97 – 104
Bece­rra A, Bellido D, Luengo A, Pie­drola G, De Luis DA. Lipoprotein(a) and other lipo­pro­teins in hypothy­roid patients before and after thy­roid repla­ce­ment the­rapy. Clin Nutr. 1999 Oct;18(5):319 – 22
Mish­kel MA, Crowther SM.Hypothyroidism, an impor­tant cause of rever­si­ble hyper­li­pi­de­mia. Clin Chim Acta. 1977 Jan 17;74(2):139 – 51

Athe­rosc­le­ro­sis: the asso­cia­tion with lower thy­roid hor­mone levels

90. Imai­zumi M, Akahoshi M, Ichi­maru S, Nakashima E, Hida A, Soda M, Usa T, Ashi­zawa K, Yoko­yama N, Maeda R, Naga­taki S, Eguchi K. Risk for ische­mic heart disease and all-cause mor­ta­lity in subc­li­ni­cal hypothy­roi­dism. J Clin Endoc­ri­nol Metab. 2004 Jul;89(7):3365 – 70
91. Myas­ni­kov AL, Myas­ni­kov LA, Zai­tzev VF. The influence of thy­roid hor­mo­nes on cho­les­te­rol meta­bo­lism in expe­ri­men­tal athe­rosc­le­ro­sis in rab­bits. J Athe­rosc­ler Res. 1963 Jul-Aug;37:295 – 300

Athe­rosc­le­ro­sis: the impro­ve­ment with thy­roid treatment

92. Papaioan­nou GI, Lagasse M, Mather JF, Thomp­son PD. Trea­ting hypothy­roi­dism impro­ves endothe­lial func­tion. Meta­bo­lism. 2004 Mar;53(3):278 – 9
93. Naga­saki T, Inaba M, Henmi Y, Kumeda Y, Ueda M, Tahara H, Sugi­guchi S, Fuji­wara S, Emoto M, Ishi­mura E, Onoda N, Ishi­kawa T, Nishi­zawa Y. D ecrease in caro­tid intima-media thick­ness in hypothy­roid patients after nor­ma­li­za­tion of thy­roid func­tion. Clin Endoc­ri­nol (Oxf). 2003 Nov;59(5):607 – 12 Myas­ni­kov AL, Myas­ni­kov LA, Zai­tzev VF. The influence of thy­roid hor­mo­nes on cho­les­te­rol meta­bo­lism in expe­ri­men­tal athe­rosc­le­ro­sis in rab­bits. J Athe­rosc­ler Res. 1963 Jul-Aug;37:295 – 300

Arte­rial hyper­ten­sion: the asso­cia­tion with lower thy­roid hor­mone levels

94. Biondi B, Klein I. Hypothy­roi­dism as a risk fac­tor for car­dio­vas­cu­lar disease. Endoc­rine. 2004 Jun;24(1):1 – 13
95. Stree­ten DH, Ander­son GH Jr, How­land T, Chiang R, Smul­yan H. Effects of thy­roid func­tion on blood pres­sure. Recog­ni­tion of hypothy­roid hyper­ten­sion. Hyper­ten­sion. 1988 Jan;11(1):78 – 83
96. Fom­mei E, Ier­vasi G. The role of thy­roid hor­mone in blood pres­sure homeos­ta­sis: evi­dence from short-term hypothy­roi­dism in humans. J Clin Endoc­ri­nol Metab. 2002 May;87(5):1996 – 2000
97. Saito I, Ito K, Saruta T. Hypothy­roi­dism as a cause of hyper­ten­sion. Hyper­ten­sion. 1983 Jan-Feb;5(1):112 – 5

Arte­rial hyper­ten­sion: the impro­ve­ment with thy­roid treatment

98. Fuller H Jr, Spit­tell JA Jr, McCo­nahey WM, Schir­ger A. Myxe­dema and hyper­ten­sion. Post­grad Med. 1966 Oct;40(4):425 – 8
Gasio­rowski W, Pla­zinska MT. Arte­rial hyper­ten­sion asso­cia­ted with hyper and hypothy­roi­dism. Pol Tyg Lek. 1992 Nov 2 – 9;47(44 – 45):1009 – 10
Odd­zialu Tera­pii Izo­to­po­wej Zakladu Medycyny Nuklear­nej CSK MSW, Warszawie.

Coro­nary heart disease: the asso­cia­tion with lower thy­roid hor­mone levels

99. Miura S, Iitaka M, Suzuki S, Fuka­sawa N, Kitahama S, Kawa­kami Y, Saka­tsume Y, Yama­naka K, Kawa­saki S, Kinoshita S, Kata­yama S, Shi­bo­sawa T, Ishii J. Dec­rease in serum levels of thy­roid hor­mone in patients with coro­nary heart disease. Endocr J. 1996 Dec;43(6):657 – 63

Coro­nary heart disease and other car­diac disea­ses: the impro­ve­ment with thy­roid treatment

100. Bar­nes BO. Prophy­la­xis of ischae­mic heart-disease by thy­roid the­rapy. Lan­cet. 1959 Aug 22;2:149 – 52
101. Holland FW 2^nd, Brown PS Jr, Clark RE. Acute severe pos­tische­mic myo­car­dial depres­sion rever­sed by triio­dothy­ro­nine. Ann Tho­rac Surg. 1992 Aug;54(2):301 – 5
102. Fack­tor MA, Mayor GH, Nach­rei­ner RF, D’Alecy LG. Thy­roid hor­mone loss and repla­ce­ment during resus­ci­ta­tion from car­diac arrest in dogs. Resus­ci­ta­tion. 1993 Oct;26(2):141 – 62
103. Israel M. An effec­tive the­ra­peu­tic approach to the con­trol of athe­rosc­le­ro­sis illus­tra­ting harm­less­ness of pro­lon­ged use of thy­roid hor­mone in coro­nary disease. Am J Dig Dis. 1955 June;161 – 8

Car­dio­vas­cu­lar disease and mor­ta­lity: inc­rea­sed in hypothy­roi­dism (+ 70 % for both)
Dorr M, Volzke H. Car­dio­vas­cu­lar mor­bi­dity and mor­ta­lity in thy­roid dys­func­tion. Minerva Endoc­ri­nol. 2005 Dec;30(4):199 – 216
Depart­ment of Inter­nal Medi­cine B, Ernst-Moritz-Arndt-University, Greifs­wald, Germany

Stroke and other cere­bro­vas­cu­lar disor­ders: the asso­cia­tion with lower thy­roid hor­mone levels

104. Hu R. Chan­ges in serum thy­roid hor­mo­nes in acute cere­bro­vas­cu­lar apo­plexy and their cli­ni­cal sig­ni­fi­cance. Zhonghua Shen Jing Jing Shen Ke Za Zhi. 1990 Apr;23(2):87 – 9, 126
105. Ben­venga S, Mor­gante L, Bar­ta­lena L, Manna L, Li Calzi L, Coraci MA, Tri­marchi F. Serum thy­roid hor­mo­nes and thy­roid hor­mone bin­ding pro­teins in patients with com­ple­ted stroke. Ann Clin Res. 1986;18(4):203 – 7

Obe­sity: the asso­cia­tion with lower thy­roid hor­mone levels

106. Resta O, Pan­nac­ciu­lli N, Di Gioia G, Ste­fano A, Bar­baro MP, De Per­gola G. High pre­va­lence of pre­viously unk­nown subc­li­ni­cal hypothy­roi­dism in obese patients refe­rred to a sleep cli­nic for sleep disor­de­red breathing. Nutr Metab Car­dio­vasc Dis. 2004 Oct;14(5):248 – 53
107. Jung CH, Sung KC, Shin HS, Rhee EJ, Lee WY, Kim BS, Kang JH, Kim H, Kim SW, Lee MH, Park JR, Kim SW. Thy­roid dys­func­tion and their rela­tion to car­dio­vas­cu­lar risk fac­tors such as lipid pro­file, hsCRP, and waist hip ratio in Korea. Korean J Intern Med. 2003 Sep;18(3):146 – 53
108. Rimm AA, Wer­ner LH, Yser­loo BV, Berns­tein RA. Rela­tionship of ove­sity and disease in 73,532 weight-conscious women. Public Health Rep. 1975 Jan-Feb;90(1):44 – 54

Obe­sity: the impro­ve­ment with thy­roid treatment

109. Moore R, Grant AM, Howard AN, Mills IH. Treat­ment of obe­sity with triio­dothy­ro­nine and a very-low-calorie liquid for­mula diet. Lan­cet. 1980 Feb 2;1(8162):223 – 6
110. Gel­vin EP, Kenigs­berg S, Boyd LJ. Results of addi­tion of liothy­ro­nine to a weight-reducing regimen.J Am Med Assoc. 1959 Jul 25;170(13):1507 – 12
111. Rozen R, Abraham G, Fal­cou R, Apfel­baum M. Effects of a ‘phy­sio­lo­gi­cal’ dose of triio­dothy­ro­nine on obese sub­jects during a protein-sparing diet. Int J Obes. 1986;10(4):303 – 12
112. Pas­quali R, Baraldi G, Biso P, Piazzi S, Patrono D, Cape­lli M, Melchionda N. Effect of ‘phy­sio­lo­gi­cal’ doses of triio­dothy­ro­nine repla­ce­ment on the hor­mo­nal and meta­bo­lic adap­ta­tion to short-term semis­tar­va­tion and to low-calorie diet in obese patients. Clin Endoc­ri­nol (Oxf). 1984 Oct;21(4):357 – 67
113. Kop­peschaar HP, Mein­ders AE, Sch­warz F. Meta­bo­lic res­pon­ses in grossly obese sub­jects trea­ted with a very-low-calorie diet with and without triio­dothy­ro­nine treat­ment. Int J Obes. 1983;7(2):133 – 41
114. Kop­peschaar HP, Mein­ders AE, Sch­warz F. The effect of a low-calorie diet alone and in com­bi­na­tion with triio­dothy­ro­nine the­rapy on weight loss and hypophy­seal thy­roid func­tion in obe­sity. Int J Obes. 1983;7(2):123 – 31
115. Wil­son JH, Lam­berts SW. The effect of triio­dothy­ro­nine on weight loss and nitro­gen balance of obese patients on a very-low-calorie liquid-formula diet. Int J Obes. 1981;5(3):279 – 82
116. Moore R, Meh­rishi JN, Ver­doorn C, Mills IH. The role of T3 and its recep­tor in effi­cient meta­bo­li­sers recei­ving very-low-calorie diets. Int J Obes. 1981;5(3):283 – 6
117. Moore R, Grant AM, Howard AN, Mills IH. Treat­ment of obe­sity with triioi­dothy­ro­nine and a very low cao­rie liquid for­mula diet. Lan­cet 1980 Feb. 2;223 – 6

Dia­be­tes: The asso­cia­tion with lower thy­roid hor­mone levels

118. Perros P, McC­rim­mon RJ, Shaw G, Frier BM. Fre­quency of thy­roid dys­func­tion in dia­be­tic patients: value of annual scree­ning. Dia­bet Med. 1995 Jul;12(7):622 – 7
119. Alvarez-Marfany M, Roman SH, Drex­ler AJ, Rober­tson C, Stagnaro-Green A. Long-term pros­pec­tive study of post­par­tum thy­roid dys­func­tion in women with insu­lin depen­dent dia­be­tes melli­tus. J Clin Endoc­ri­nol Metab. 1994 Jul;79(1):10 – 6
120. Lam­berg; B-A. Glu­cose meta­bo­lism in thy­roid disease. Acta Med Scand. 1965178: 351
121. ELRICK H, HLAD CJ Jr, ARAI Y. Influence of thy­roid func­tion on car­bohy­drate meta­bo­lism and a new method for asses­sing res­ponse to insu­lin. J Clin Endoc­ri­nol Metab. 1961 Apr;21:387 – 400

Dia­be­tes: the impro­ve­ment with thy­roid treatment

122. Hous­say BA. The thy­roid and dia­be­tes. Vitam Horm. 1946;4:188
123. Eaton CD. Coe­xis­tence of hypothy­roi­dism with dia­be­tes melli­tus. J Mich State Med Soc. 1954 Oct;53(10, Part 1):1101

Rheu­ma­tism: the asso­cia­tion with lower thy­roid hor­mone levels

124. Herr­mann F, Hambsch K, Sor­ger D, Hantzschel H, Muller P, Nagel I. Low T3 syn­drome and chro­nic inflam­ma­tory rheu­ma­tism. Z Gesamte Inn Med. 1989 Sep 1;44(17):513 – 8
538. Shi­roky JB, Cohen M, Ballachey ML, Nevi­lle C. Thy­roid dys­func­tion in rheu­ma­toid arth­ri­tis: a con­tro­lled pros­pec­tive sur­vey. Ann Rheum Dis. 1993 Jun;52(6):454 – 6
539. Neeck G, Rie­del W. Thy­roid func­tion in patients with fibrom­yal­gia syn­drome. J Rheu­ma­tol. 1992 Jul;19(7):1120 – 2
540. Magaro M, Zoli A, Alto­monte L, Mirone L, La Sala L, Barini A, Scu­deri F. The asso­cia­tion of silent thy­roi­di­tis with active sys­te­mic lupus erythe­ma­to­sus. Clin Exp Rheu­ma­tol. 1992 Jan-Feb;10(1):67 – 70

Rheu­ma­tism: the impro­ve­ment with thy­roid treatment

1032. Klop­pen­burg M, Dijk­mans BA, Ras­ker JJ. Effect of the­rapy for thy­roid dys­func­tion on mus­cu­los­ke­le­tal symp­toms. Clin Rheu­ma­tol. 1993 Sep;12(3):341 – 5
1033. Gledhill RF, Des­sein PH, Van der Merwe CA. Treat­ment of Raynaud’s phe­no­me­non with triio­dothy­ro­nine corrects co-existent auto­no­mic dys­func­tion: pre­li­mi­nary fin­dings. Post­grad Med J. 1992 Apr;68(798):263 – 7

Osteo­po­ro­sis: the impro­ve­ment with thy­roid treatment

1065. Svan­berg E, Hea­ley J, Mas­ca­renhas D. Ana­bo­lic effects of rhIGF-I/IGFBP-3 in vivo are influen­ced by thy­roid sta­tus. Eur J Clin Invest. 2001 Apr;31(4):329 – 36.

Can­cer: the asso­cia­tion with lower thy­roid hor­mone levels

619. Shel­ton BK. Hypothy­roi­dism in can­cer patients. Nurse Pract Forum. 1998 Sep;9(3):185 – 91
620. Mellem­gaard A, From G, Jor­gen­sen T, Johan­sen C, Olsen JH, Perrild H. Can­cer risk in indi­vi­duals with benign thy­roid disor­ders. Thy­roid. 1998 Sep;8(9):751 – 4
621. Liechty RD, Hod­ges RD, Bur­ket J. Can­cer and thy­roid func­tion. JAMA. 1963 Jan 5;183:30 – 2.
Tellini U, Pelliz­zari L, Pra­va­de­lli B. Thy­roid func­tion in elderly with neo­plasms. Minerva Med. 1999 Apr;90(4):111 – 21
622. She­ring SG, Zbar AP, Moriarty M, McDer­mott EW, O’Higgins NJ, Smyth PP. Thy­roid disor­ders and breast can­cer. Eur J Can­cer Prev 1996 Dec;5(6):504 – 6

Can­cer: the impro­ve­ment with thy­roid treatment?

1100. Sch­wartz SBS. The rela­tionship of thy­roid defi­ciency to can­cer: a 50-year retros­pec­tive study. J IAPM, 1977, 6 (1):9 – 21
1101. Lacka K. Treat­ment with L-thyroxine for dif­fe­ren­tia­ted thy­roid car­ci­noma. Wiad Lek. 2001;54 Suppl 1:368 – 72

Lon­ge­vity: the asso­cia­tion with thy­roid hor­mone

660. Ceri­llo AG, Bevi­lac­qua S, Storti S, Mariani M, Kallushi E, Ripoli A, Cle­rico A, Glau­ber M. Free triio­dothy­ro­nine: a novel pre­dic­tor of pos­to­pe­ra­tive atrial fibri­lla­tion. Eur J Car­diotho­rac Surg. 2003 Oct;24(4):487 – 92
661. Ier­vasi G, G, Pin­gi­tore A, Landi P, Raciti M, Ripoli A, Scar­lat­tini M, L’Abbate A, Donato L. Low T3 syn­drome: a strong pre­dic­tor of death in patients with heart disease. Cir­cu­la­tion. 2003; 107(5): 708 – 13
Koz­dag G, Ural D, Vural A, Agac­di­ken A, Kah­ra­man G, Sahin T, Ural E, Kom­suo­glu B. Rela­tion bet­ween free triiodothyronine/free thy­ro­xine ratio, echo­car­dio­graphic para­me­ters and mor­ta­lity in dila­ted car­diom­yo­pathy. Eur J Heart Fail. 2005 Jan;7(1):113 – 8
Depart­ment of Car­dio­logy, Kocaeli Uni­ver­sity, Yah­ya­kap­tan Mah. A4 Blok Daire:3, Kocaeli 41050, Tur­key. gkozdag@superonline.com
Pin­gi­tore A, Landi P, Tad­dei MC, Ripoli A, L’Abbate A, Ier­vasi G. Triio­dothy­ro­nine levels for risk stra­ti­fi­ca­tion of patients with chro­nic heart fai­lure. Am J Med. 2005 Feb;118(2):132 – 6
Ins­ti­tute of Cli­ni­cal Phy­sio­logy, C.N.R., Pisa, Italy. pingi@ifc.cnr.it 

Thy­roid Diagnosis:

Fre­quency of overt and subc­li­ni­cal hypothyroidism

1. Van­der­pump MP, Tun­bridge WM, French JM, Apple­ton D, Bates D, Clark F, Grim­ley Evans J, Hasan DM, Rod­gers H, Tun­bridge F, et al. The inci­dence of thy­roid disor­ders in the com­mu­nity: a twenty-year follow-up of the Whickham Sur­vey. Clin Endoc­ri­nol (Oxf). 1995 Jul;43(1):55 – 68
2. Wier­singa WM. Subc­li­ni­cal hypothy­roi­dism and hyperthy­roi­dism. I. Pre­va­lence and cli­ni­cal rele­vance. Neth­Jof­Med 1994;46:197 – 204

Serum thy­roid tests

Laden­son PW. Opti­mal labo­ra­tory tes­ting for diag­no­sis and moni­to­ring of thy­roid nodu­les, goi­ter, and thy­roid can­cer. Clin Chem. 1996 Jan;42(1):183 – 7
Divi­sion of Endoc­ri­no­logy and Meta­bo­lism, Johns Hop­kins Uni­ver­sity School of Medi­cine, Bal­ti­more, MD 21287 – 4904, USA. ladenson@welchlink.welch.jhu.edu

Serum TSH

Nunez S, Lec­lere J. Diag­no­sis of hypothy­roi­dism in the adult. Rev Prat. 1998; 48(18): 1993 – 8.
van Coe­vor­den A, Moc­kel J, Lau­rent E, Kerkhofs M, L’Hermite-Baleriaux M, Decos­ter C, Neve P, Van Cau­ter E. Neu­roen­doc­rine rhythms and sleep in aging men. Am J Phy­siol. 1991 Apr;260(4 Pt 1):E651-61
Greens­pan SL, Kli­banski A, Rowe JW, Elahi D. Age-related alte­ra­tions in pul­sa­tile sec­re­tion of TSH: role of dopa­mi­ner­gic regu­la­tion. Am J Phy­siol. 1991 Mar;260(3 Pt 1):E486-91
Beth Israel Hos­pi­tal, Bos­ton
Her­toghe T. Poor Relia­bi­lity of the sin­gle Plasma TSH-test for diag­no­sis of thy­roid dys­func­tion and follow-up. Anti-Aging Medi­cal The­ra­peu­tics, 2000, Ed. Klatz R & Gold­man R, publi­ca­tion of the Ame­ri­can Aca­demy of Anti-Aging Medi­cine & Health Quest Publi­ca­tions, Marina del Rey, CA 

Serum Thy­ro­xine and Triiodothyronine 

Zucche­lli GC, Pilo A, Chiesa MR, Masini S. Sys­te­ma­tic dif­fe­ren­ces bet­ween com­mer­cial immu­noas­says for free thy­ro­xine and free triio­dothy­ro­nine in an exter­nal qua­lity assess­ment pro­gram. Clin Chem. 1994 Oct;40(10):1956 – 61.
Sol­din OP, Hilakivi-Clarke L, Wei­der­pass E, Sol­din SJ. Trimester-specific refe­rence inter­vals for thy­ro­xine and triio­dothy­ro­nine in preg­nancy in iodine-sufficient women using iso­tope dilu­tion tan­dem mass spec­tro­metry and immu­noas­says. Clin Chim Acta. 2004 Nov;349(1 – 2):181 – 9. 

Serum thy­roid antibodies

Lian XL, Bai Y, Sun ML, Guo ZS, Dai WX. Cli­ni­cal vali­dity of anti-thyroperoxidase anti­body and anti-thyroglobulin anti­body. Zhong­guo Yi Xue Ke Xue Yuan Xue Bao. 2004 Dec;26(6):677 – 81
Depart­ment of Endoc­ri­no­logy, PUMC Hos­pi­tal, CAMS and PUMC, Bei­jing 100730, China. lianlanx@public.bta.ner.cn
Engler H, Rie­sen WF, Keller B. Anti-thyroid pero­xi­dase (anti-TPO) anti­bo­dies in thy­roid disea­ses, non-thyroidal ill­ness and con­trols. Cli­ni­cal vali­dity of a new com­mer­cial method for detec­tion of anti-TPO (thy­roid mic­ro­so­mal) autoan­ti­bo­dies. Clin Chim Acta. 1994 Mar;225(2):123 – 36
Ins­ti­tute of Cli­ni­cal Che­mistry and Hae­ma­to­logy, St. Gallen, Swi­tzer­land
Caron P, Babin T, Oks­man F, Hoff M. Anti-thyroid pero­xi­dase in non-neoplastic thy­roid patho­logy]
Rev Med Interne. 1991 Sep-Oct;12(5):335 – 8 (“Anti-thyroid pero­xi­dase anti­bo­dies ..their level dec­rea­sed during repla­ce­ment the­rapy for hypothy­roi­dism”)
Depar­te­ment d’Endocrinologie et Mala­dies Meta­bo­li­ques, CHU Ran­gueil, Tou­louse, France.
39. Hel­fand M, Crapo LM. Moni­to­ring the­rapy in patients taking levothy­ro­xine. Ann Intern Med. 1990; 113:450 – 454.
Aksoy DY, Keri­mo­glu U, Okur H, Can­pi­nar H, Karaa­gao­glu E, Yet­gin S, Kansu E, Gedik O. Effects of prophy­lac­tic thy­roid hor­mone repla­ce­ment in euthy­roid Hashimoto’s thy­roi­di­tis. Endocr J. 2005 Jun;52(3):337 – 43 (After 15 months of L-thyroxine treat­ment, there was a sig­ni­fi­cant inc­rease in free T4 and a sig­ni­fi­cant dec­rease in TSH and anti-thyroglobulin anti­body anti-thyroid pero­xi­dase anti­body
Levels, and a dec­rease in thy­roid volume, whe­reas an inc­rease was detec­ted in patients who were follo­wed without treat­ment)
Sec­tion of Endoc­ri­no­logy and Meta­bo­lism, Depart­ment of Inter­nal Medi­cine,
Hacet­tepe Uni­ver­sity, Ankara, Turkey.

Serum TRH test

Bin­de­ba­lle W, Gute­kunst R, Lahrtz H, Rabenhorst G, Schem­mel K. Diag­no­sis and con­trol of the­rapy of thy­roid disor­ders by TRH-test. Med Klin. 1975 Mar 21;70(12):505 – 9

Chai­lur­kit L, Raja­ta­na­vin R. Com­pa­ri­son of basal serum TSH con­cen­tra­tion by immu­no­ra­dio­me­tric assay and TRH sti­mu­la­tion test in the diag­no­sis of thy­roid dys­func­tion. J Med Assoc Thai. 1990 Jun;73(6):329 – 34
Depart­ment of Medi­cine, Faculty of Medi­cine, Ramathi­bodi Hos­pi­tal, Mahi­dol Uni­ver­sity, Bang­kok, Thai­land.
Ishihara T, Aka­mizu T, Sawada K, Ike­kubo K, Mori T. Use­ful­ness of the TRH-T3 test in the diag­no­sis of cen­tral hypothy­roi­dism. Nip­pon Nai­bunpi Gak­kai Zasshi. 1983 Aug 20;59(8):1131 – 7
Bot­ter­mann P, Glog­ger C, Hen­der­kott U. Intra­ve­nous and oral TRH-stimulation test: com­pa­ri­son of the value of both tests con­cer­ning diag­no­sis and the­rapy of thy­roid disea­ses. Med Klin. 1979 Oct 12;74(41):1485 – 91

24-hour urine Thy­roid Hormones

1. Fra­ser WD, Big­gart E, O’Reilly D St J, Gray H W, McKi­llop JH, Thom­son JA. Are bioche­mi­cal tests of thy­roid func­tion of any value in moni­to­ring patients recei­ving thy­ro­xine repla­ce­ment? Br Med J. 1986, 293: 808 – 10
2. Chan V, Lan­don J. Uri­nary thy­ro­xine exc­re­tion as index of thy­roid func­tion. Lan­cet. 1972, (Jan 1) 7740: 4 – 6
3. Tal E , Sul­man FG. Uri­nary thy­ro­xine. Lan­cet. 1972, 1291
4. Chan V, Bes­ser GM, Lan­don J, Ekins RP. Uri­nary triio­dothy­ro­nine exc­re­tion as index of thy­roid func­tion. Lan­cet 1972, (Aug 5) 253 – 256
5. Chan V, Bes­ser GM, Lan­don J. Effects of oes­tro­gen on uri­nary thy­ro­xine exc­re­tion. Br Med J. 1972, 4: 699 – 701
6. Ras­togi GK, Sawh­ney, Sinha, Tho­mas, Devi. Serum and uri­nary levels of thy­roid hor­mo­nes in nor­mal preg­nancy. Obs­tet Gyne­col. 1974, 2: 176 – 80
7. Rogowski P,Siersbaek-Nielsen K, Mölholm Han­sen J. Uri­nary exc­re­tion of thy­ro­xine in dif­fe­rent thy­roid sta­tes. Acta Endoc­ri­nol (Kopenh). 1978, 87: 525 – 34
8. Kolen­dorf K, Broch Môller B, Rogowski P. The influence of chro­nic renal fai­lure on serum and uri­nary thy­roid hor­mone levels. Acta Endoc­ri­nol (Kopenh). 1978, 89: 80 – 8
9. Ali Afra­siaki M, Dabir Vaziri N, Grant Gwi­nup, Mays M, Bar­ton CH, Ness RL,Valenta LJ. Thy­roid func­tion in the neph­ro­tic syn­drome. Ann Int Med. 1979, 90, 335 – 8
10. Aizawa T, Yamada T, Tawata M, Shi­mizu T, Furuta S, Kiyo­sawa K, Yakata M. Thy­roid hor­mone meta­bo­lism in patients with liver cirrho­sis, as jud­ged by urnary exc­re­tion of triio­dothy­ro­nine. J Am Geria­trics Soc. 1980;28(11):485 – 91
11. Yoshida K, Saku­rada T, Kaise K, Saito S, Yoshi­naga K. Mea­su­re­ment of triio­dothy­ro­nine in urine. Tohoku J Exp Med. 1980;132(4):389 – 95
12. Lopresti JS, Warren DW, Kap­tein EM, Crox­son MS, Nico­loff JT. Uri­nary immu­no­pre­ci­pi­ta­tion method for esti­ma­tion of thy­ro­xine to triio­dothy­ro­nine con­ver­sion in alte­red thy­roid sta­tes. J Clin Endoc­ri­nol Metab. 1982;55( 4):666 – 70
13. Yoshida K, Saku­rada T, Kaise K, Yama­moto M, Saito S, Yoshi­naga K. Thy­roid sti­mu­la­tion test with uri­nary T3 con­cen­tra­tion as an index of thy­roid res­ponse. Tohuku J Exp Med. 1983;139(3):271 – 7
14. Mirralles-Garcia JM, Mories-Alvarez MT, Reglero-Chillon A, Lanao JM, Corrales-Hernandez JJ, Garcia-Diez LC. Uri­nary kine­tics of triio­dothy­ro­nine and their modi­fi­ca­tion with age. Horm Metab Res. 1985;17(7):366 – 9
15. Orden I, Pie, Juste, Mar­se­lla, Blasco. Thy­ro­xine in unex­trac­ted urine. Acta Endoc­ri­nol (Kopenh). 1987;114:503 – 8
16. Faber J, Siersbaek-Nielsen K, Kir­ke­gaard C. Renal hand­ling of thy­ro­xine, 3,5,3’- and 3,3’,5’-triiodothyronine, 3,3’-diiodothyronine in man. Acta Endoc­ri­nol (Kopenh). 1987;115:144 – 8
17. Orden I, Pie J, Juste MG, Giner A, Gomez ME, Esca­nero JF. Uri­nary triio­dothy­ro­nine exc­re­tion. Rev Espan Fisiol. 1988;44 (2):179 – 84
18. Her­toghe J. The use­ful­ness of eva­lua­ting the uri­nary exc­re­tion of triio­dothy­ro­nine and thy­ro­xine in the uri­nes of 24 hours for diag­no­sis of thy­roid dys­func­tion and follow-up of thy­roid treat­ment. Con­fe­rence in Ant­werp, Bel­gium, March 1975
19. Bai­sier WV, Her­toghe J,Eeckhaut W. Thy­roid insuf­fi­ciency. Is TSH the only diag­nos­tic tool? J Nutr Env Med. 2000; 10: 105 – 13
20. Bai­sier WV, Her­toghe J, Eeckhaut W. Thy­roid insuf­fi­ciency. Is thy­ro­xine the only valuale drug? J Nutr Env Med. 2001;11:159 – 166
21. Her­toghe T. The effi­cacy of diag­no­sing bor­der­line and overt hypothy­roi­dism with the labo­ra­tory assess­ment of triio­dothy­ro­nine and thy­ro­xine exc­re­tion in the uri­nes of 24 hours. A com­pa­ri­son with plasma thy­roid tests. Opti­mal hor­mone the­rapy in the aging adult. Basic and advan­ced semi­nar, San Fran­cisco, February, 2000

Correc­tive Thy­roid Therapy

Thy­roid medications

Alley RA, Danowski TS, Rob­bins TJ, Weir TF, Sabeh G, Moses CL Indi­ces during admi­nis­tra­tion of T4 and T3 to euthy­roid adults. Meta­bo­lism. 1968 Feb;17(2):97 – 104 (equi­va­len­cies bet­ween T4, T3, T3 + T4, des­sic­ca­ted thy­roid preparations)

Thy­ro­xine

48. Oppenhei­mer JH, Bra­ver­man LE, Toft A, Jack­son, IM, Laden­son, PW. Thy­roid hor­mone treat­ment when and what? J Clin Endoc­ri­nol Metab. 1995;80:2873 – 83
49. Dong BJ, Brown CH. Hypothy­roi­dism resul­ting from gene­ric levothy­ro­xine fai­lure. J Am Board Fam. Pract. l991;4:167 – 70
6. Roti E, Mine­lli R, Gar­dini E, Bra­ver­man LE. The use of misuse of thy­roid hor­mone. Endoc­rine Rev. 1993;14:401 – 23
7. Toft AD. Thy­ro­xine the­rapy. N Engl J Med. 1994 Jul 21;331(3):174 – 80
8. USP Dis­pen­sing Infor­ma­tion: Volume 1– Drug Infor­ma­tion for Health Care Pro­fes­sio­nals. The Uni­ted Sta­tes Phar­ma­co­peial Con­ven­tion, Rock­vi­lle, MD, 1997
38. Ridg­way EC, McCam­mon JA, Benotti J, Maloof F. Acute meta­bo­lic res­pon­ses in myxe­dema to large doses of intra­ve­nous L-thyroxine. Ann Intern Med. 1972;77:549 – 55

Thyroxine-Triiodothyronine asso­cia­tions

Rees-Jones RW, Lar­sen PR. Triio­dothy­ro­nine and thy­ro­xine con­tent of desic­ca­ted thy­roid tablets. Meta­bo­lism. 1977 Nov;26(11):1213 – 8
Man­gieri CN, Lund MH. Potency of Uni­ted Sta­tes Phar­ma­co­peia des­si­ca­ted thy­roid tablets as deter­mi­ned by the anti­goi­tro­ge­nic assay in rats. J Clin Endoc­ri­nol Metab. 1970 Jan;30(1):102 – 4
Gaby AR. Sub-laboratory hypothy­roi­dism and the empi­ri­cal use of Armour thy­roid. Altern Med Rev. 2004 Jun;9(2):157 – 79
Her­toghe T, Lo Cas­cio A., Her­toghe J. Con­si­de­ra­ble impro­ve­ment of hypothy­roid symp­toms with two com­bi­ned T3-T4 medi­ca­tion in patients still symp­to­ma­tic with thy­ro­xine treat­ment alone. Anti-Aging Medi­cine (Ed. Ger­man Society of Anti-Aging Medicine-Verlag 2003) 2004; 32 – 43
Her­toghe T. Many con­di­tions rela­ted to age reduce the con­ver­sion of thy­ro­xine to triio­dothy­ro­nine — a ratio­nale for presc­ri­bing pre­fe­ren­tially a com­bi­ned T3 + T4 pre­pa­ra­tion in hypothy­roid adults. Anti-Aging Medi­cal The­ra­peu­tics 2000; IV: 138 – 53

Fre­quency of use of thy­roid hormones

9. Kauf­man SC, Gross GP, Ken­nedy DL. Thy­roid hor­mone use: trends in the Uni­ted Sta­tes from 1960 through 1988. Thy­roid 1997; 1:285 – 91
100. . Sawin CT, Geller A, Hersh­man JM, Cas­te­lli W, Bacha­rach P. The aging thy­roid: the use of thy­roid hor­mone in older per­sons. JAMA 1989;261:2653 – 5

Thy­roid dosage

11. Fish LH, Sch­wartz HL, Cava­naugh J, Stef­fes MW, Bantle JP. Repla­ce­ment dose, meta­bo­lism, and bioa­vai­la­bi­lity of levothy­ro­xine in the treat­ment of hypothy­roi­dism. Role of triio­dothy­ro­nine in pitui­tary feed­back in humans. N Engl J Med. 1987:316:764 – 70
47. Carr D, McLeod DT, Parry G, Thor­nes HM. Fine adjust­ment of thy­ro­xine repla­ce­ment dosage: com­pa­ri­son ofthelhy­ro­trophin relea­sing hor­mone test using a sen­si­tive thy­ro­tro­pin assay with mea­su­re­ment of free thy­roid hor­mo­nes and cli­ni­cal assess­ment. Clin Endoc­ri­nol (Oxf). 1988:28:325 – 33
40. Grebe SK, Cooke RR, Ford HC, Fagers­trom JN, Cord­well DP, Lever NA, Pur­die GL, Feek CM. Treat­ment of hypothy­roi­dism with once weekly thy­ro­xine. J Clin Endoc­ri­nol Metab. 1997 Mar;82(3):870 – 5
61. Kabadi UM. Opti­mal daily levothy­ro­xine dose in pri­mary hypothy­roi­dism. Its rela­tion to pre-treatment thy­roid hor­mone inde­xes. Arch Intern Med. 1990;149:2209 – 12
62. Man­del SJ, Lar­sen PR, Seely EW, Brent GA. Inc­rea­sed need for thy­ro­xine during preg­nancy in women with pri­mary hypothy­roi­dism. N Engl J Med. 1990:323:91 – 6
63. Kaplan MM. Moni­to­ring thy­ro­xine treat­ment during preg­nancy. Thy­roid. 1992:2:147 – 52
64. Sin­ger PA. Thy­roi­di­tis acute, suba­cute, and chro­nic. Med Clin North Am. 1991:75:61 – 77
81. Bano­vac K, Carring­ton SAB, Levis S, Fill MD, Bils­ker MS. Deter­mi­na­tion of repla­ce­ment and sup­pres­sive doses ofthy­ro­xine. J Intern Med Res. 1990; 18:210 – 8
35. Sawin CT, Her­man T, Molitch ME, Lon­don MH, Kra­mer SM. Aging and the thy­roid. Dec­rea­sed requi­re­ment for chy­roid hor­mone in older hypothy­roid patients. Am J Med. 1983;75:206 – 9
36. Fisher DA. Mana­ge­ment of con­ge­ni­tal hypothy­roi­dism. J Clin Endoc­ri­nol Metab 1991;72:523 – 9
37. Bear­coft CP, Toms GC, Williams SJ, Noo­nan K, Mon­son JP. Thy­ro­xine repla­ce­ment in post-radioiodine hypothy­roi­dism. Clin Endoc­ri­nol. 1991;34:115 – 8

Thy­roid hor­mone absorp­tion and malabsorption 

13. Hays MT, Niel­sen KRK. Human thy­ro­xine absorp­tion: age effects and metho­do­lo­gi­cal analy­ses. Thy­roid. 1994:4:55 – 64
14. Wen­zel KW, Kirschei­per HE. Aspects of the absorp­tion of oral 1-thyroxine in nor­mal man. Meta­bo­lism. 1977;26:1 – 8
15. Ben­venga S, Bar­to­lone L, Squa­drito S, Lo Giu­dice F, Tri­marchi F. Dela­yed intes­ti­nal absorp­tion of levothy­ro­xine. Thy­roid. 1995;5(4):249 – 53
16. Read DG, Hays MT, Hersh­man JM. Absorp­tion of oral thy­ro­xine in hypothy­roid and nor­mal man. J Clin Endoc­ri­nol Metab. 1970;30:798 – 9
17. Azizi F, Belur R, Albano J. Malab­sorp­tion of thy­roid hor­mo­nes after jeju­noi­leal bypass for obe­sity. Ann Intern Med. 1979;90:941 – 2
18. Bevan JS, Munro JF. Thy­ro­xine malab­sorp­tion follo­wing intes­ti­nal bypass sur­gery. Int J Obes. 1986; 10:245 – 6
19. Stone E, Lei­ter LA, Lam­bert JR, Sil­ver­berg JDH, Jee­yeebhoy KN, Burrow GN. L-Thyroxine absorp­tion in patients with short bowel. J Clin Endoc­ri­nol Metab. 1984;59:139 – 41
20. Ain KB, Refe­toff S, Fein HG, Wein­traub BD. Pseu­do­ma­lab­sorp­tion of levothy­ro­xine. JAMA 1991;266:2118 – 20
21. North­cutt RC, Stiel JN, Holli­fiels JW, Stant EG. The influence of cho­lesty­ra­mine on thy­ro­xine absorp­tion. JAMA. 1969;208:1857 – 61
22. Har­mon SM, Sie­fert CF. Levothyroxine-cholestyramine inte­rac­tion reempha­si­zed. Ann Intern Med. 1991;115:658 – 9
23. Sper­ber AD, Liel Y. Evi­dence for inter­face with the intes­ti­nal absorp­tion of levothy­ro­xine sodium by alu­mi­num hydro­xide. Arch Intern Med 1992; 152:183 – 4
24. Camp­bell NR, Hasi­noff BB, Stalts H, Rao B, Wong NC. Ferrous sul­fate redu­ces thy­ro­xine effi­cacy in patients with hypothy­roi­dism. Ann Intern Med. 1992;117:1010 – 3
25. Sher­man SI, Tie­lens E, Laden­son PW. Suc­ral­fate cau­ses malab­sorp­tion of L-thyroxine. Am J Med. 1994;96:531 – 5
26. Liel Y, Harman-Boehm I, Shany S. Evi­dence for a cli­ni­cally impor­tant adverse effect of fiber-enriched diet on the bioa­vai­la­bi­lity of levothy­ro­xine in adult hypothy­roid patients. J Clin Endoc­ri­nol Metab. 1996:80:857 – 9

Thy­roid treat­ment: safety, spe­cial con­di­tions to care­fully watch for 

67. Klein I, Oja­maa K. Thy­roid hor­mone and the heart. Am J Med. 1996;101:459 – 60
68. Kea­ting FR, Par­kin TW, Selby JB, Dic­kin­son LS. Treat­ment of heart disease asso­cia­ted with myxe­dema. Prog Car­dio­vasc Dis. 1960;3:364 – 81
69. Wein­berg AD, Bren­nan MD, Ger­man CA, Marsh HM, O’Fallon WM. Out­come of anesthe­sia and sur­gery in hypothy­roid patients. Arch Intern Med. 1983;143:893 – 897
70. Laden­son PW, Levin AA, Ridg­way EC, Daniels GH. Com­pli­ca­tions of sur­gery in hypothy­roid patients. Am J Med. 1984;77:261 – 6
Bauer M, Priebe S, Bergho­fer A, Bschor T, Kiess­lin­ger U, Why­brow PC. Sub­jec­tive res­ponse to and tole­ra­bi­lity of long-term supraphy­sio­lo­gi­cal doses of levothy­ro­xine in refrac­tory mood disor­ders. J Affect Disord. 2001 Apr;64(1):35 – 42 (“Sub­jec­tive res­ponse and side-effect tole­ra­bi­lity of long-term supraphy­sio­lo­gi­cal doses (mean dose 368 µg/day for a mean of 54 months)of T4 is favo­ra­ble in patients with refrac­tory mood and schi­zoaf­fec­tive disor­ders who res­pond to the intervention”)

Thy­roid Treat­ment: side effects, complications

41. Paul TL, Kerri­gan J, Kelly AM, Bra­ver­man LE, Baran DT. Long-term L-thyroxine the­rapy is asso­cia­ted with dec­rea­sed hip bone den­sity in pre­me­no­pau­sal women. JAMA. 1988;259:3137 – 41
42. Stall GM, Harris S, Sokoll LJ, Dawson-Hughes B. Acce­le­ra­ted bone loss in hypothy­roid patients over trea­ted with con­tem­po­rary pre­pa­ra­tions. Ann Intern Med 1990; 105:11 – 5
43. Greens­pan SL, Greens­pan FS, Res­nick NM, Block JE, Fried­lan­der AL, Genant HK. Ske­le­tal inte­grity in pre­me­no­pau­sal and post­me­no­pau­sal women recei­ving long-term L-thyroxine the­rapy Am J Med. 1991;91:5 – 14
44. Franklyn JA, Bet­te­ridge J, Day­kin J, Hol­der R, Oates GD, Parle JV, et al. Long-term thy­ro­xine treat­ment and bone mine­ral den­sity. Lan­cet. 1992;340:9 – 13
45. Sch­nei­der DL, Barrett-Connor EL, Mor­ton DJ. Thy­roid hor­mone use and bone mine­ral den­sity in elderly women. JAMA. 1994;271:1245 – 9
46. Sawin CT, Geller A, Wolk PA, et al. Low serum thy­ro­tro­pin con­cen­tra­tion as a risk fac­tor for atrial fibri­lla­tion in older per­sons. N Engi J Med. 1994;331:1249 – 52
79. Shi­bata H, Haya­kawa H, Hiru­kawa M, Tado­koro K, Ogata E. Hyper­sen­si­ti­vity cau­sed by synthe­tic thy­roid hor­mo­nes in a hypothy­roid patient with Hashimoto’s thy­roi­di­tis. Arch Intern Med. 1986; 146:1624 – 5
80. Mag­ner J, Ger­ber P. Urti­ca­ria due to blue dye in synth­roid tablets. Thy­roid. 1994 Fall;4(3):341 

Thy­roid Treat­ment inter­fe­ren­ces or associations

33. Ara­fah BM. Dec­rea­sed levothy­ro­xine requi­re­ment in women with hypothy­roi­dism during andro­gen the­rapy for breast can­cer. Ann Intern Med. 1994; 121:247 – 51
34. Rosen­baum RL, Bar­zel US. Levothy­ro­xine repla­ce­ment dose for pri­mary hypothy­roi­dism dec­rea­ses with age. Ann Intern Med. 1982:96:53 – 5
Mishell DR Jr, Colodny SZ, Swan­son LA. The effect of an oral con­tra­cep­tive on tests of thy­roid func­tion. Fer­til Ste­ril. 1969 Mar-Apr;20(2):335 – 9

Thy­roid treat­ment follow-up

Fra­ser WD, Big­gart EM, O’Reilly DS, Gray HW, McKi­llop JH, Thom­son JA. Are bioche­mi­cal tests of thy­roid func­tion of any value in moni­to­ring patients recei­ving thy­ro­xine repla­ce­ment? Br Med J (Clin Res Ed). 1986 Sep 27;293(6550): 293 – 808
39. Hel­fand M, Crapo LM. Moni­to­ring the­rapy in patients taking levothy­ro­xine. Ann Intern Med. 1990; 113:450 – 4
27. Brow­ning MC, Ben­net WM, Kir­kaldy AJ, Jung RT. Intra-individual varia­tion of thy­ro­xine, triio­dothy­ro­nine, and thy­ro­tro­pin in trea­ted hypothy­roid patients: impli­ca­tions for moni­to­ring repla­ce­ment the­rapy. Clin Chem. 1988;34:696 – 9
28. Ain KB, Pucino F, Shi­ver TM, Banks SM. Thy­roid hor­mone levels affec­ted by time of blood sam­pling
in thyroxine-treated patients. Thy­roid. 1993;3:81 – 5

TOPICS OF DISCUSSION

DISCUSSIONS ON THYROID DIAGNOSIS 

SERUM TSH: IS THE TSH TEST SUFFICIENT FOR DIAGNOSIS AND FOLLOW-UP OF THYROID DEFICIENCY?

Claim: TSH is the first line test to do. It is suf­fi­cient to diag­nose all forms of eu-, hypo– and hyperthy­roi­dism. No other test is neces­sary for the diagnosis.

Facts: TSH is often insuf­fi­cient on its own to diag­nose bet­ween eu-, hypo– and hyperthy­roi­dism, par­ti­cu­larly to diag­nose mil­der, bor­der­line sta­tes of hypothy­roi­dism. Other tests are neces­sary, as is a com­plete cli­ni­cal eva­lua­tion (medi­cal his­tory, actual com­plaints, phy­si­cal examination)

TSH: often con­si­de­red as first line approach to diag­nose thy­roid dysfunction

Nunez S, Lec­lere J. Diag­no­sis of hypothy­roi­dism in the adult. Rev Prat. 1998; 48(18): 1993 – 8.

Ove­rre­liance on labo­ra­tory tests without cli­ni­cal eva­lua­tion may lead to con­si­de­ra­ble diag­nos­tic errors

Nico­loff JT, Spen­cer CA. The use and misuse of the sen­si­tive thy­ro­tro­pin assay. J Clin Endoc­ri­nol Metab. 1990;71:553 – 8.
De Los San­tos ET, Maz­za­fe­rri EL. Sen­si­tive thyroid-stimulating hor­mone assays: Cli­ni­cal appli­ca­tions and limi­ta­tions. Compr Ther. 1988; 14(9): 26 – 33.
Bec­ker DV, Bigos ST, Gai­tan E, Morris JCrd, ralli­son ML, Spen­cer CA, Suga­rawa M, Van Midd­les­worth L, War­tofsky L. Opti­mal use of blood tests for assess­ment of thy­roid func­tion. JAMA 1993 Jun 2; 269: 273 (“the deci­sion to ini­tiate the­rapy shoul be based on both cli­ni­cal and labo­ra­tory fin­dings and not solely on the results of a sin­gle labo­ra­tory test”)

Dis­cus­sions and con­tro­versy in medi­cal asso­cia­tions and jour­nals on TSH refe­rence range

Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hersh­man JM, Bur­man KD, Denke MA, Gor­man C, Coo­per RS, Weiss­man NJ. Subc­li­ni­cal thy­roid disease: scien­ti­fic review and gui­de­li­nes for diag­no­sis and mana­ge­ment. JAMA. 2004;291:228 – 38 (conc­lu­sions of a con­sen­sus panel of the Endoc­rine Society, the Ame­ri­can Thy­roid Association,and Ame­ri­can Asso­cia­tion of Cli­ni­cal Endoc­ri­no­logy. Although the panel conc­lu­ded that there was good data that patients with slight ele­va­tions of TSH above 4.5 may pro­gress to overt hypothy­roi­dism, and that levothy­ro­xine the­rapy would pre­vent symp­toms, they did not agree that early treat­ment pro­vi­ded any bene­fit!)
Dic­key RA, War­tofsky L, Feld S. Opti­mal thy­ro­tro­pin level: nor­mal ran­ges and refe­rence inter­vals are not equi­va­lent. Thy­roid. 2005 Sep;15(9):1035 – 9
War­tofsky L, Dic­key RA. The evi­dence for a narro­wer thy­ro­tro­pin refe­rence range is com­pe­lling. J Clin Endoc­ri­nol Metab. 2005 Sep;90(9):5483 – 8
Gha­rib H, Tuttle RM, Bas­kin HJ, Fish LH, Sin­ger PA, McDer­mott MT. Subc­li­ni­cal thy­roid dys­func­tion: a joint sta­te­ment on mana­ge­ment from the Ame­ri­can Asso­cia­tion of Cli­ni­cal Endoc­ri­no­lo­gists, the Ame­ri­can Thy­roid Asso­cia­tion, and The Endoc­rine Society. J Clin Endoc­ri­nol Metab. 2005;90:581 – 5
Surks MI. Com­men­tary: subc­li­ni­cal thy­roid dys­func­tion: a joint sta­te­ment on mana­ge­ment from the Ame­ri­can Asso­cia­tion of Cli­ni­cal Endoc­ri­no­lo­gists, the Ame­ri­can Thy­roid Asso­cia­tion, and The Endoc­rine Society. J Clin Endoc­ri­nol Metab. 2005;90:586 – 7
Rin­gel MD, Maz­za­fe­rri EL. Edi­to­rial: subc­li­ni­cal thy­roid dys­func­tion: can there be a con­sen­sus about the con­sen­sus? J Clin Endoc­ri­nol Metab. 2005;90:588 – 90
Pinchera A. Subc­li­ni­cal thy­roid disease: to treat or not to treat? Thy­roid. 2005;15:1 – 2

Data indi­ca­ting a popu­la­tion mean value of 1.5 mU/liter for an iodine-sufficient population

6. Van­der­pump MPJ, Tun­bridge WMG, French JM, Apple­ton D, Bates D, Clark F, Grim­ley Evans J, Hasan DM, Rod­gers H, Tun­bridge F. The inci­dence of thy­roid disor­ders in the com­mu­nity: a twenty-year follow-up of the Whickham Sur­vey. Clin Endoc­ri­nol (Oxf). 1995;43:55 – 68
7. Hollo­well JG, Staeh­ling NW, Flan­ders WD, Gun­ter EW, Spen­cer CA, Bra­ver­man LE. Serum TSH, T4, and thy­roid anti­bo­dies in the Uni­ted Sta­tes popu­la­tion (1988 to 1994): Natio­nal Health and Nutri­tion Exa­mi­na­tion Sur­vey (NHANES III). J Clin Endoc­ri­nol Metab. 2002; 87:489 – 99
8. Ander­sen S, Peter­sen KM, Brunn NH, Laur­berg P. Narrow indi­vi­dual varia­tions in serum T4 and T3 in nor­mal sub­jects: a clue to the unders­tan­ding of subc­li­ni­cal thy­roid disease. J Clin Endoc­ri­nol Metab. 2002;87:1068 – 72
9. Demers LM, Spen­cer CA. Labo­ra­tory medi­cine prac­tice gui­de­li­nes: labo­ra­tory sup­port for the diag­no­sis and moni­to­ring of thy­roid disease. Clin Endoc­ri­nol (Oxf). 2003;58:138 – 40
10. Baloch Z, Cara­yon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spen­cer CA, Stoc­kigt JR, Gui­de­li­nes Com­mit­tee, Natio­nal Aca­demy of Cli­ni­cal Bioche­mistry 2003 Labo­ra­tory medi­cine prac­tice gui­de­li­nes. Labo­ra­tory sup­port for the diag­no­sis and moni­to­ring of thy­roid disease. Thy­roid. 2003 Jan;13(1):3 – 126

Lon­gi­tu­di­nal stu­dies indi­ca­ting a rate of pro­gres­sion of mild thy­roid fai­lure into overt hypothy­roi­dism of about 5% per year (50% or more in 10 years!)

6. Van­der­pump MPJ, Tun­bridge WMG, French JM, Apple­ton D, Bates D, Clark F, Grim­ley Evans J, Hasan DM, Rod­gers H, Tun­bridge F. The inci­dence of thy­roid disor­ders in the com­mu­nity: a twenty-year follow-up of the Whickham Sur­vey. Clin Endoc­ri­nol (Oxf). 1995; 43:55 – 68
11. Parle JV, Franklyn JA, Cross KW, Jones SC, Shep­pard MC. Pre­va­lence and follow-up of abnor­mal thy­ro­trophin (TSH) con­cen­tra­tions in the elderly in the Uni­ted King­dom. Clin Endoc­ri­nol (Oxf). 1991;34:77 – 83
12. Huber G, Staub J-J, Meier C, Mitrache C, Gugliel­metti M, Huber P, Bra­ver­man LE. Pros­pec­tive study of the spon­ta­neous course of subc­li­ni­cal hypothy­roi­dism: prog­nos­tic value of thy­ro­tro­pin, thy­roid reserve, and thy­roid anti­bo­dies. J Clin Endoc­ri­nol Metab. 2002;87:3221 – 6
13. Kabadi UM. ‘Subc­li­ni­cal hypothy­roi­dism:’ natu­ral course of the syn­drome during a pro­lon­ged follow-up study. Arch Intern Med. 1993;153:957 – 61

Lon­gi­tu­di­nal study in dia­be­tics : base­line TSH levels > 1.53 mU/liter pre­dic­ted sub­se­quent thy­roid dys­func­tion, whe­reas no thy­roid dys­func­tion if TSH levels < 1.53 mU/liter

25. Warren RE, Perros P, Nyi­renda MJ, Frier BM. Serum thy­ro­tro­pin is a bet­ter pre­dic­tor of future thy­roid dys­func­tion than thy­roid autoan­ti­body sta­tus in bioche­mi­cally euthy­roid patients with dia­be­tes: impli­ca­tions for scree­ning. Thy­roid. 2004;14:853 – 7

Assu­ring a refe­rence inter­val for TSH that is more truly nor­mal and should have a nor­mal Gaus­sian dis­tri­bu­tion. The recom­men­da­tion would be to draw upon a cohort of indi­vi­duals with no per­so­nal or family his­tory of thy­roid dys­func­tion, no visi­ble or pal­pa­ble goi­ter, who are taking no medi­ca­tion, whose blood sam­ples are drawn fas­ting in the mor­ning hours (06 – 10 h), and who are sero­ne­ga­tive for thy­roid preo­xi­dase anti­bo­dies. When data for sub­jects with posi­tive antithy­roid anti­bo­dies or a family his­tory of autoim­mune thy­roid disease are exc­lu­ded from a so-called nor­mal cohort, the nor­mal refe­rence range beco­mes 0.4 – 2.5 mU/L(Demers & co, Baloch & co.)

9. Demers LM, Spen­cer CA. Labo­ra­tory medi­cine prac­tice gui­de­li­nes: labo­ra­tory sup­port for the diag­no­sis and moni­to­ring of thy­roid disease. Clin Endoc­ri­nol (Oxf). 2003;58:138 – 40
10. Hollo­well JG, Staeh­ling NW, Flan­ders WD, Gun­ter EW, Spen­cer CA, Bra­ver­man LE. Serum TSH, T4, and thy­roid anti­bo­dies in the Uni­ted Sta­tes popu­la­tion (1988 to 1994): Natio­nal Health and Nutri­tion Exa­mi­na­tion Sur­vey (NHANES III). J Clin Endoc­ri­nol Metab. 2002; 87:489 – 99
10. Baloch Z, Cara­yon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spen­cer CA, Stoc­kigt JR, Gui­de­li­nes Com­mit­tee, Natio­nal Aca­demy of Cli­ni­cal Bioche­mistry 2003 Labo­ra­tory medi­cine prac­tice gui­de­li­nes. Thy­roid. 2003 Jan;13(1):3 – 126

Impro­ved new refe­rence range if per­sons with dif­fuse hypoecho­ge­ni­city of the thy­roid on ultra­sound would be exc­lu­ded in view of the recent fin­ding that this pre­ce­des TPOAb posi­ti­vity in autoim­mune thy­roid disease

26. Peder­sen OM, Aar­dal NP, Lars­sen TB, Varhaug JE, Myking O, Vik-Mo H. The value of ultra­so­no­graphy in pre­dic­ting autoim­mune thy­roid disease. Thy­roid. 2000;10:251 – 9 

Revi­sed refe­rence TSH range of 0.3 – 3.0 mU/L of the Ame­ri­can Asso­cia­tion of Cli­ni­cal Endocrinologists 

27. Ame­ri­can Asso­cia­tion of Cli­ni­cal Endoc­ri­no­lo­gists. Ame­ri­can Asso­cia­tion of Cli­ni­cal Endoc­ri­no­lo­gists medi­cal gui­de­li­nes for cli­ni­cal prac­tice for the eva­lua­tion and treat­ment of hyperthy­roi­dism and hypothy­roi­dism. Endocr Pract. 2002;8:457 – 69

The value of a population-based refe­rence range is limi­ted when the indi­vi­dual patient-based refe­rence range(i.e. their per­so­nal refe­rence range) is narrow

28. Fra­ser CG, Harris EK. Gene­ra­tion and appli­ca­tion of data on bio­lo­gi­cal varia­tion in cli­ni­cal che­mistry. Crit Rev Clin Lab Sci. 1989;27:409 – 37
29. Harris EK. Effects of intra– and inte­rin­di­vi­dual varia­tion on the appro­priate use of nor­mal ran­ges. Clin Chem. 1974;20:1535 – 42

Indi­vi­dual TSH refe­rence ran­ges are remar­kably narrow within a rela­ti­vely small seg­ment of the popu­la­tion refe­rence range, i.e. con­fi­ned to only 25% of a range of 0.3 – 5.0 mU/liter. 

A shift in the TSH value of the indi­vi­dual outside of his or her indi­vi­dual refe­rence range, but still within the popu­la­tion refe­rence range, would not be nor­mal for that indi­vi­dual. For exam­ple, an indi­vi­dual (as in Anderson’s series) with a per­so­nal range of 0.5 – 1.0 mU/liter would be at subphy­sio­lo­gi­cal thy­roid hor­mone levels at the popu­la­tion mean TSH of 1.5 mU/liter. 

Ander­sen S, Peter­sen KM, Brunn NH, Laur­berg P. Narrow indi­vi­dual varia­tions in serum T4 and T3 in nor­mal sub­jects: a clue to the unders­tan­ding of subc­li­ni­cal thy­roid disease. J Clin Endoc­ri­nol Metab. 2002;87:1068 – 72 

Stu­dies of twins indi­cate that each of us has a gene­ti­cally deter­mi­ned opti­mal free T4 (FT4)-TSH set point or rela­tionship

9; Demers LM, Spen­cer CA. Labo­ra­tory medi­cine prac­tice gui­de­li­nes: labo­ra­tory sup­port for the diag­no­sis and moni­to­ring of thy­roid disease. Clin Endoc­ri­nol (Oxf). 2003;58:138 – 40
30. Mei­kle AW, Stringham JD, Wood­ward MG, Nel­son JC. Here­di­tary and envi­ron­men­tal influen­ces on the varia­tion of thy­roid hor­mo­nes in nor­mal male twins. J Clin Endoc­ri­nol Metab. 1988 ; 66:588 – 92 

A mea­su­red TSH dif­fe­rence of 0.75 mU/liter can already be sig­ni­fi­cant in a patient. The NACB gui­de­line 8 sta­tes that “.. the mag­ni­tude of dif­fe­rence in … TSH… values that would be cli­ni­cally sig­ni­fi­cant when moni­to­ring a patient’s res­ponse to the­rapy… is 0.75 mU/liter. Grea­ter TSH fluc­tua­tions in a spe­ci­fic patient may mean the patient beco­mes hypothy­roid or hyperthyroid 

11. Baloch Z, Cara­yon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spen­cer CA, Stoc­kigt JR, Gui­de­li­nes Com­mit­tee, Natio­nal Aca­demy of Cli­ni­cal Bioche­mistry 2003 Labo­ra­tory medi­cine prac­tice gui­de­li­nes. Thy­roid. 2003 Jan;13(1):3 – 126

Eth­nic dif­fe­ren­ces: the mean TSH level in African-Americans is 1.18 mU/liter, in con­trast to a mean of 1.40 mU/liter in Cau­ca­sians, due to the grea­ter fre­quency of autoim­mune thy­roid disease in whi­tes (12.3%) than in blacks (4.3%), which may have unjus­ti­fiedly ske­wed the upper end of the TSH curve (NHANES data)

7. Hollo­well JG, Staeh­ling NW, Flan­ders WD, Gun­ter EW, Spen­cer CA, Bra­ver­man LE. Serum TSH, T4, and thy­roid anti­bo­dies in the Uni­ted Sta­tes popu­la­tion (1988 to 1994): Natio­nal Health and Nutri­tion Exa­mi­na­tion Sur­vey (NHANES III). J Clin Endoc­ri­nol Metab. 2002;87:489 – 9 

A study, which sug­gests that the a serum TSH cut-off point bet­ween hypo– and euthy­roi­dism is 2, not 4 or 5.5 (Trea­ting TPO antibody-positive hypercho­les­te­ro­le­mic patients with TSH levels bet­ween 2 – 4 mU/L with low dose levothy­ro­xine nor­ma­li­zes TSH levels and impro­ves the lipid profile)

Micha­lo­pou­lou G, Ale­vi­zaki M, Pipe­rin­gos G, Mitsi­bou­nas D, Man­tzos E, Adam­pou­los P, Kou­tras DA. High serum cho­les­te­rol levels in per­sons with ‘high-normal’ TSH levels: Should one extend the defi­ni­tion of subc­li­ni­cal hypothy­roi­dism? Eur J Endoc­ri­nol. 1998 Feb;138(2):141 – 5

When data for sub­jects with posi­tive TPOAb or a family his­tory of autoim­mune thy­roid disease are exc­lu­ded, the nor­mal refe­rence inter­val beco­mes much tigh­ter, i.e. 0.4 – 2.0 mU/liter (7, 9) This tigh­ter refe­rence range may cer­tainly be more appli­ca­ble to African-Americans, who have a lower mean TSH 

31. Hollo­well JG, Staeh­ling NW, Flan­ders WD, Gun­ter EW, Spen­cer CA, Bra­ver­man LE. Serum TSH, T4, and thy­roid anti­bo­dies in the Uni­ted Sta­tes popu­la­tion (1988 to 1994): Natio­nal Health and Nutri­tion Exa­mi­na­tion Sur­vey (NHANES III). J Clin Endoc­ri­nol Metab. 2002; 87:489 – 99
9. Demers LM, Spen­cer CA. Labo­ra­tory medi­cine prac­tice gui­de­li­nes: labo­ra­tory sup­port for the diag­no­sis and moni­to­ring of thy­roid disease. Clin Endoc­ri­nol (Oxf). 2003;58:138 – 40 

Recog­ni­tion of the need to tigh­ten up the refe­rence range for TSH has led to the Natio­nal Aca­demy of Cli­ni­cal Bioche­mistry (NACB) redu­cing the upper limit of the refe­rence range from 5.5 to 4.1 mU/L, but sta­ting also that “grea­ter than 95% of healthy, euthy­roid sub­jects have a serum TSH con­cen­tra­tion bet­ween 0.4 — 2.5 mU/L”. “.. patients with a serum TSH >2.5 mU/L, when con­fir­med by repeat TSH mea­su­re­ment made after 3 to 4 weeks, may be in the early sta­ges of thy­roid fai­lure, espe­cially if thy­roid pero­xi­dise anti­bo­dies are detected”

10. Baloch Z, Cara­yon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spen­cer CA, Stoc­kigt JR, Gui­de­li­nes Com­mit­tee, Natio­nal Aca­demy of Cli­ni­cal Bioche­mistry 2003 Labo­ra­tory medi­cine prac­tice gui­de­li­nes. Thy­roid. 2003 Jan;13(1):3 – 126

A serum TSH that rises in a given indi­vi­dual from a set point of 1.0 to 3.5 is likely to be abnor­mally ele­va­ted and imply early thy­roid failure. 

A minor change in serum free T4 results in an ampli­fied change in TSH to outside of the usual population-based refe­rence range, although the free T4 is still within its own population-based refe­rence range, because of the the log-linear rela­tionship bet­ween TSH and free T4. 

In the case of subc­li­ni­cal hypothy­roi­dism, for exam­ple, a slight drop in free T4 results in an ampli­fied and inverse res­ponse in TSH secretion

31. Coo­per DS. Subc­li­ni­cal hypothy­roi­dism. N Engl J Med. 2001;345:260 – 5
32. Ayala A, War­tofsky L. Mini­mally symp­to­ma­tic (subc­li­ni­cal) hypothy­roi­dism. Endoc­ri­no­lo­gist. 1997;7:44 – 50 

There is a 3-fold dif­fe­rence bet­ween the ave­rage daily maxi­mum (3) and mini­mum (1 mIU/ml)

89. Bra­bant G, Prank K, Ranft U, Schuer­me­yer T, Wag­ner TO, Hau­ser H, Kum­mer B,
Feist­ner H, Hesch RD, von zur Muh­len A. Phy­sio­lo­gi­cal regu­la­tion of cir­ca­dian and pul­sa­tile thy­ro­tro­pin sec­re­tion in nor­mal man and woman. J Clin Endoc­ri­nol Metab. 1990 Feb;70(2):403 – 9

TSH refe­rence range is too large => need for narro­wer ranges

Pain RW. Sim­ple modi­fi­ca­tions of three rou­tine in vitro tests of thy­roid func­tion. Clin Chem. 1976; 22(10): 1715 – 8.
Dic­key RA, War­tofsky L, Feld S. Opti­mal thy­ro­tro­pin level: nor­mal ran­ges and refe­rence inter­vals are not equi­va­lent. Thy­roid. 2005 Sep;15(9):1035 – 9
War­tofsky L, Dic­key RA. The evi­dence for a narro­wer thy­ro­tro­pin refe­rence range is com­pe­lling. J Clin Endoc­ri­nol Metab. 2005 Sep;90(9):5483 – 8
Fre­quency of abnor­mal TSH values
34. Cana­ris GJ, Mano­witz NR, Mayor G, Ridg­way EC. The Colo­rado thy­roid disease pre­va­lence study. Arch Intern Med. 2000;160:526 – 34
25. Warren RE, Perros P, Nyi­renda MJ, Frier BM. Serum thy­ro­tro­pin is a bet­ter pre­dic­tor of future thy­roid dys­func­tion than thy­roid autoan­ti­body sta­tus in bioche­mi­cally euthy­roid patients with dia­be­tes: impli­ca­tions for scree­ning. Thy­roid. 2004;14:853 – 7

The pitui­tary 5’-deiodinase type 2 that con­verts thy­ro­xine into triio­dothy­ro­nine (T3), is dif­fe­rent than the liver and kid­ney 5’-deiodinase type 1 that pro­vi­des the T3 for the rest of the body. This dif­fe­rence may explain why TSH sec­re­tion and thus serum TSH sec­re­ted by the pitui­tary gland may be nor­mal, while the rest of the body may be in a thy­roid defi­cient state.

1. Koe­nig RJ, Leo­nard JL, Sena­tor D, Rap­pa­port N, Watson A, Lar­sen PR. Regu­la­tion of thy­ro­xine 5′-deiodinase acti­vity by 3,5,3′-triiodothyronine in cul­tu­red ante­rior pitui­tary cells. Endoc­ri­no­logy. 1984 Jul;115(1):324 – 9.

In fas­ting, hypothy­roi­dism or sele­nium defi­ciency for exam­ple, the 5‘-deiodinase of the pitui­tary gland inc­rea­ses or remains unchan­ged, while that of the liver decreases.

2. Suda AK, Pitt­man CS, Shi­mizu T, Cam­bers JB. The pro­duc­tion and meta­bo­lism of 3,5,3′-triiodothyronine and 3,3′,5′-triiodothyronine in nor­mal and fas­ting sub­jects. J Clin Endoc­ri­nol Metab. 1978 Dec;47(6):1311 – 9
3. Lar­sen PR, Silva JE, Kaplan MM. Rela­tionships bet­ween cir­cu­la­ting and intra­ce­llu­lar thy­roid hor­mo­nes: Phy­sio­lo­gi­cal and cli­ni­cal impli­ca­tions. Endocr Rev. 1981 Winter;2(1):87 – 102.
4. Cha­noine JP, Safran M, Far­well AP, Tran­ter P, Eken­bar­ger DM, Dubord S, Arthur JR, Bec­kett GJ, Bra­ver­man LE Dubord S, Alex S, Arthur JR, Bec­kett GJ, Bra­ver­man LE, Leo­nard JLl. Sele­nium defi­ciency and type II 5′-deiodinase regu­la­tion in the euthy­roid and hypothy­roid rat: evi­dence of a direct effect of thy­ro­xine. Endoc­ri­no­logy. 1992 Jul;131(1):479 – 84

A nor­mal or low serum TSH may reflect in elderly per­sons hypothy­roi­dism in periphe­ral tis­sues, and not any­more eu– or hyperthy­roi­dism, because the pitui­tary gland has aged. Pro­gres­si­vely with inc­rea­sing age, the serum TSH test beco­mes less relia­ble as a diag­nos­tic test.

5. Urban RJ. Neu­roen­doc­ri­no­logy of aging in the male and female. Endoc­ri­nol Metab Clin North Am. 1992;21(4): 921 – 31.
Neces­sity for other tests than the TSH to diag­no­sis thy­roid dys­func­tion, e.g. the serum free T4
6. Laden­son PW. Diag­no­sis of hypothy­roi­dism. In Wer­ner and Ingbar’s The Thy­roid, 7^th edi­tion, Bra­ver­man LE and Uti­ger RE, Lippincott-Raven Publishers, Phi­la­delphia. 1996; 878 – 82
7. Pacchia­rotti A, Mar­tino E, Bar­ta­lena L, Aghini Lom­bardi F, Grasso L, Buratti L, Fal­cone M, Pinchera A. Serum free thy­roid hor­mo­nes in subc­li­ni­cal hypothy­roi­dism. J Endoc­ri­nol Invest. 1986 Aug;9(4):315 – 9
8. Surks MI, Cho­pra IJ, Mariosh CN, Nico­loff JT, Salo­mon DH. Ame­ri­can Thy­roid Asso­cia­tion gui­de­li­nes for use of labo­ra­tory tests in thy­roid disor­ders. JAMA. 1990 Mar 16;263(11):1529 – 32
9. Davis JR, Black EG, Shep­pard MC. Eva­lua­tion of a sen­si­tive che­mi­lu­mi­nes­cent assay for TSH in the follow-up of trea­ted thy­ro­to­xi­co­sis. Clin Endoc­ri­nol Oxf. 1987; 27(5): 563 – 70

Serum thy­roid hor­mone levels may not reflect the cellu­lar thy­roid status

10. Esco­bar del Rey F, Ruiz de Ona C, Ber­nal J, Obre­gon MJ, Morreale de Esco­bar G. Gene­ra­li­zed defi­ciency of 3, 5, 3′-triiodothyronine in tis­sues from rats on a low iodine intake, des­pite nor­mal cir­cu­la­ting T3 levels. Acta Endoc­ri­nol (Copenh) 1989; 120: 490 – 8

Need to analyse valua­ble indi­ca­tors of periphe­ral acti­vity such as the serum levels of plasma bin­ding pro­teins SHBG, TBG, CBG, or of thyroid-dependent enzy­mes such as alka­line phospha­tase, osteocalcin

11. Small­ridge RC. Meta­bo­lic, phy­sio­lo­gic, and cli­ni­cal inde­xes of thy­roid func­tion. In Wer­ner and Ingbar’s The Thy­roid, 7^th edi­tion, Bra­ver­man LE and Uti­ger RP, Lippincott-Raven Publishers, Phi­la­delphia, 1996
12. Fol­des J, Tar­jan G, Banos C, Nemeth J, Varga F, Buki B. Bio­lo­gic mar­kers in blood reflec­ting thy­roid hor­mone effect at periphe­ral tis­sue level in patients recei­ving levothy­ro­xine repla­ce­ment for hypothy­roi­dism. Exp Clin Endoc­ri­nol. 1992; 99(3): 129 – 33

Serum TSH test for follow-up: The risk of misin­ter­pre­ta­tion inc­rea­ses when moni­to­ring the treat­ment of hyper– or hypothyroidism

114. Tal­bot JN, Duron F, Feron R. Aubert P, Milhaud G. Thy­ro­glo­bu­lin, thy­ro­tro­pin and thy­ro­tro­pin bin­ding inhi­bi­ting immu­no­glo­bu­lins assa­yed at the with­dra­wal of antithy­roid drug the­rapy as pre­dic­tors of relapse of Gra­ves’ disease within one year. J Endoc­ri­nol Invest. 1989; 12(9): 589 – 95

In 36 – 47 % of cini­cally euthy­roid patients recei­ving ade­quate long-term thy­roid the­rapy for hypothy­roi­dism, an unde­tec­ta­ble serum TSH is found

47. Franklyn JA, Black EG, Bet­te­ridge J, Shep­pard MC. Com­pa­ri­son of second and third gene­ra­tion methods for mea­su­re­ment of serum thy­ro­tro­pin in patients with overt hyperthy­roi­dism, patients recei­ving thy­ro­xine the­rapy, and those with nonthy­roi­dal ill­ness. J Clin Endoc­ri­nol Metab 1994; 78(6): 1368 – 71
48. Gow SM, Cald­well G, Toft AD, Seth J, Hus­sey AJ, Swee­ting VM, Bec­kett GJ. Rela­tionship bet­ween pitui­tary and other tar­get organ res­pon­si­ve­ness in hypothy­roid patients recei­ving thy­ro­xine repla­ce­ment. J Clin Endoc­ri­nol Metab. 1987; 64(2): 364 – 70

After intake of thy­roidhor­mo­nes , the serum TSH is tran­si­to­rily depres­sed within 60 minu­tes and remains low for up to 9hours after intake

51. Cho­pra U, Carl­son HE, Solo­mon DH. Com­pa­ri­son of inhi­bi­tory effects of 3,5,3′-triiodothyronine (T3), thy­ro­xine (T4), 3,3,’,5′-triiodothyronine (rT3,), and 3,3′-diiodothyronine (T2) on thyrotropin-releasing hormone-induced release of thy­ro­tro­pin in the rat in vitro. Endoc­ri­no­logy. 1978;103(2):393 – 402

Some patents who exhi­bit rever­sion of an ini­tially high TSH level back into the refe­rence range, are found to sub­se­quently deve­lop mild thy­roid failure

24. Cala­ciura F, Motta RM, Mis­cio G, Fichera G, Leo­nardi D, Carta A, Trichitta V, Tassi V, Sava L, Vig­neri R. Subc­li­ni­cal hypothy­roi­dism in early childhood: a fre­quent out­come of tran­sient neo­na­tal hyperthy­ro­tro­pi­ne­mia. J Clin Endoc­ri­nol Metab. 2002;87:3209 – 14

Sup­por­ters of the recom­men­da­tions of the con­sen­sus panel pro­mote a tar­get TSH range of 1.0 – 1.5 mU/liter in patients already recei­ving T4 the­rapy, whe­reas they refuse to accept TSH levels of 3 – 10 mU/liter as abnor­mal in patients not recei­ving T4 therapy. 

10. Baloch Z, Cara­yon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spen­cer CA, Stoc­kigt JR, Gui­de­li­nes Com­mit­tee, Natio­nal Aca­demy of Cli­ni­cal Bioche­mistry 2003 Labo­ra­tory medi­cine prac­tice gui­de­li­nes. Thy­roid. 2003 Jan;13(1):3 – 126

The lower end of the nor­mal or refe­rence range for TSH lies bet­ween 0.2 and 0.4 mU/liter, as indi­ca­ted by a num­ber of cli­ni­cal studies 

10. Baloch Z, Cara­yon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spen­cer CA, Stoc­kigt JR, Gui­de­li­nes Com­mit­tee, Natio­nal Aca­demy of Cli­ni­cal Bioche­mistry 2003 Labo­ra­tory medi­cine prac­tice gui­de­li­nes. Thy­roid. 2003 Jan;13(1):3 – 126
11. Parle JV, Franklyn JA, Cross KW, Jones SC, Shep­pard MC. Pre­va­lence and follow-up of abnor­mal thy­ro­trophin (TSH) con­cen­tra­tions in the elderly in the Uni­ted King­dom. Clin Endoc­ri­nol (Oxf). 1991;34:77 – 83
25 Warren RE, Perros P, Nyi­renda MJ, Frier BM. Serum thy­ro­tro­pin is a bet­ter pre­dic­tor of future thy­roid dys­func­tion than thy­roid autoan­ti­body sta­tus in bioche­mi­cally euthy­roid patients with dia­be­tes: impli­ca­tions for scree­ning. Thy­roid. 2004;14:853 – 7
34. Cana­ris GJ, Mano­witz NR, Mayor G, Ridg­way EC. The Colo­rado thy­roid disease pre­va­lence study. Arch Intern Med. 2000;160:526 – 34
49. Sawin CT, Geller A, Kaplan MM, Bacha­rach P, Wil­son PW, Hersh­man JM. Low serum thy­ro­tro­pin (thy­roid sti­mu­la­ting hor­mone) in older per­sons without hyperthy­roi­dism. Arch Intern Med. 1991;151:165 – 8
50. Hersh­man JM, Pekary AE, Berg L, Solo­mon DH, Sawin CT Serum thy­ro­tro­pin and thy­roid hor­mone levels in elderly and middle-aged euthy­roid per­sons. J Am Geriatr Soc. 1993;41:823 – 8
51. Parle JV, Mai­son­neuve P, Shep­pare MC, Boyle P, Franklyn JA. Pre­dic­tion of all-cause and car­dio­vas­cu­lar mor­ta­lity in elderly peo­ple from one low serum thy­ro­tro­pin result: a 10-year cohort study. Lan­cet. 2001;358:861 – 5 

FACTORS that DEPRESS the serum TSH

Aging

Urban RJ. Neu­roen­doc­ri­no­logy of aging in the male and female. Endoc­ri­nol Metab Clin North Am. 1992;21(4): 921 – 31
13. Sawin CT, Geller A, Kaplan MM, Bacha­rach P, Wil­son PW, Hersh­man JM. Low serum thy­ro­tro­pin (thyroid-stimulating hor­mone) in older per­sons without hyperthy­roi­dism. Arch Intern Med. 1991; 151(1): 165 – 8

Fas­ting

14. Crox­son MS, Hall TD, Kletzky OA, Jara­mi­llo JE, Nico­loff OA. Dec­rea­sed serum thy­ro­tro­pin indu­ced by fas­ting. J Clin Endoc­ri­nol Metab. 1977; 45: 560
15. Borst GC, Osburne RC, O’Brian JT, Geor­ges LP, Bur­man KD. Fas­ting dec­rea­ses thy­ro­tro­pin res­pon­si­ve­ness to thyrotropin-releasing hor­mone: A poten­tial cause of misin­ter­pre­ta­tion of thy­roid func­tion tests in the cri­ti­cally ill. J Clin Endoc­ri­nol Metab. 1983 Aug;57(2):380 – 3
16. Camp­bell GA, Kurcz M, Marshall S, Mei­tes J. Effects of star­va­tion in rats on serum levels of follicle sti­mu­la­ting hor­mone, lutei­ni­zing hor­mone, thy­ro­tro­pin, growth hor­mone and pro­lac­tin; res­ponse to LH-releasing hor­mone and thyrotropin-releasing hor­mone. Endoc­ri­no­logy. 1977; 100(2): 580 – 7
17. Ops­tad PK. The thy­roid func­tion in young men during pro­lon­ged phy­si­cal stress and the effect of energy and sleep depri­va­tion. Clin Endoc­ri­nol. 1984; 20: 657 – 69.

Stre­nuous phy­si­cal exercise

18. Scan­lon MF, Toft AD. Regu­la­tion of thy­ro­tro­pin sec­re­tion. In Wer­ner and Ingbar’s The Thy­roid, 7^th edition

Preg­nancy (first trimester)

19. Bra­ver­man LE and Uti­ger RE, Lippincott-Raven Publi­sers, Phi­la­delphia. 1996; 220 – 40.

Depres­sion and anxiety disorders

Bar­ta­lena L, Pla­cidi GF, Mar­tino E, Fal­cone M, Pelle­grini L, Dell’Osso L, Pacchia­rotti A, Pinchera A. Noc­tur­nal serum thy­ro­tro­pin (TSH) surge and the TSH res­ponse to TSH-releasing hor­mone: dis­so­cia­ted beha­vior in untrea­ted depres­si­ves. Clin Endoc­ri­nol Metab. 1990 Sep;71(3):650 – 5.
Ins­ti­tuto di Endoc­ri­no­lo­gia, Uni­ver­sity of Pisa, Italy­Bar­ta­lena L, Pla­cidi GH, Mar­tino E,
20.
26. Rup­precht R, Rup­precht C, Rup­precht M, Noder M, Mahls­tedt J. Triio­dothy­ro­nine, thy­ro­xine, and TSH res­ponse to dexa­metha­sone in depres­sed patients and nor­mal con­trols. Biol Psychiatry. 1989;25(1): 22 – 32.
27. Maeda K, Yoshi­moto Y, Yama­dori A. Blun­ted TSH and unal­te­red PRL res­pon­ses to TRH follo­wing repea­ted admi­nis­tra­tion of TRH in neu­ro­lo­gi­cal patients: A repli­ca­tion of neu­roen­doc­rine fea­tu­res of major depres­sion. Biol Psychiatry. 1993; 33(4): 277 – 83.
28. Duval F, Macher JP, Mokrani MC. Dif­fe­rence bet­ween eve­ning and mor­ning thy­ro­tro­pin res­pon­ses to pro­ti­re­lin in major depres­sive epi­sode. Arch Gen Psychiatry. 1990; 47(5): 443 – 8.
29. Loo­sen PT, Prange AJ Jr. erum thy­ro­tro­pin res­ponse to thyrotropin-releasing hor­mone in psychia­tric patients: A review. Am J Psychiatry 1982; 139(4): 405 – 16.

Non-thyroidal disea­ses: dia­be­tes melli­tus, Cushing’s syn­drome, renal fai­lure, can­cer, myo­car­dial infarc­tion, AIDS, post-traumatic syn­dro­mes, chro­nic alcoho­lic liver disease, other illnesses

30. Devos P. Ratio­nele keuze van schild­klier­func­tie tests. Tijdschr Geneesk. 1990; 46(8): 591 – 9
31. Ale­xan­der CM, Kap­tein EM, Lum SMC, Spen­cer CA, Kumar K, Nico­loff JT. Pat­tern of reco­very of thy­roid hor­mone indi­ces asso­cia­ted with treat­ment of dia­be­tes melli­tus. J Clin Endoc­ri­nol Metab. 1982; 54: 362 – 366
32. Andrade SF, Kanitz-Ml, Povoa H Jr. Study of thy­ro­tro­pic reserve in dia­be­tics of adult type. Acta-Biol Mod Ger 1977; 36(10): 1479 – 81
33. Gon­za­lez C, Montoya-E, Jolin T. Effect of strep­to­zo­to­cin dia­be­tes on the hypotha­la­mic pitui­tary thy­roid axis in the rat. Endoc­ri­no­logy 1980; 107(6): 2099-103
34. Rossi GL, Bes­tetti GE, Ton­tis DK, Varini M. Reverse hemoly­tic pla­que assay study of lutei­ni­zing and follicle-stimulating hor­mone and thy­ro­tro­pin sec­re­tion in dia­be­tic rat pitui­tary glands. Dia­be­tes 1989; 38(10): 1301 – 6
35. Adriaanse R, Bra­bant G, Endert E, Wier­singa W. Pul­sa­tile thy­ro­tro­pin sec­re­tion in patients with Cushing’s syn­drome. Meta­bo­lism. 1994 Jun;43(6):782 – 6
36. Beyer HK-, Schus­ter P, Press­ler H. Stu­dies on hypotha­la­mic pitui­tary thy­roid regu­la­tion in hemo­dialy­sis patients. Nuklear­me­di­zin 1981;20(1):19 – 24
37. Kokei S, Inoue T, lino S. Serum free thy­roid hor­mo­nes and res­ponse of TSH to TRH in nonthy­roi­dal ill­nes­ses. Nip­pon Nai­bunpi Gak­kai Zasshi. 1986; 62(11): 1231 – 43
38. De Mari­nis L, Man­cini A, Masala R, Tor­lon­tano M, San­dric S, Bar­ba­rino A. Eva­lua­tion of pituitary-thyroid axis res­ponse to acute myo­car­dial infarct. J Endoc­ri­nol Invest. 1985; 8(6): 519 – 22
39. Ron­da­ne­lli M, Solerte SG, Fio­ra­vanti M, Sce­vola K, et al. Cir­ca­dian sec­re­tory pat­tern of growth hor­mone, insulin-like growth fac­tor type I, cor­ti­sol, adre­no­cor­ti­co­tro­pic hor­mone, thyroid-stimulating hor­mone, and pro­lac­tin during HIV infec­tion. AIDS Res Hum Retro­vi­ru­ses. 1997; 13(14): 1243 – 9.
40. Win­te­mitz WW, Dzur JA. Pitui­tary fai­lure secon­dary to head trauma. Case report. J Neu­ro­surg. 1976; 44(4): 504 – 5
41. Dzur JA, Win­te­mitz WW. Post­trau­ma­tic hypo­pi­tui­ta­rism: Ante­rior pitui­tary insuf­fi­ciency secon­dary to head trauma. South Med J. 1976; 69(10): 1377 – 9
42. Modi­gliani E, Periac P, Perret G, Hugues JN, Coste T. TRH res­ponse in 53 patients with chro­nic alcoho­lism. Ann Med Interne Paris. 1979; 130(5):297 – 302
43. Ekman AC, Vak­kuri 0, Ekman M, Lep­pa­lusto J, Ruc­ko­nen A, Knip M. Etha­nol dec­rea­ses noc­tur­nal plasma levels of thy­ro­tro­pin and growth hor­mone but not those of thy­roid hor­mo­nes or pro­tec­tion in man. J Clin Endoc­ri­nol Metab. 1996; 81(7):2627 – 32
44. Bacci V, Schuss­ler GC, Kaplan TB. The rela­tionschip bet­ween serum trii­dothy­ro­nine and thy­ro­tro­pin during sys­te­mic ill­ness. J Clin Endoc­ri­nol Metab. 1982; 54:1229 – 35
45. Ham­blin PS, Dyer SA, Mohr VS, Le Grand BA, Lim CF, Tuxen DV, Topliss DJ, Stoc­kigt JR. Rela­tionship bet­ween thy­ro­tro­pin and thy­ro­xine chan­ges during reco­very from severe hypothy­ro­xi­ne­mia of cri­ti­cal ill­ness. J Clin Endoc­ri­nol Metab. 1986 Apr;62(4):717 – 22
46. Ber­mu­dez F, Sucks MI, Opperhei­mer JH. High inci­dence of dec­rea­sed serum triio­dothy­ro­nine con­cen­tra­tion in patients with nonthy­roi­dal disease. J Clin Endoc­ri­nol Metab. 1975; 41: 27 – 40.

Medi­ca­tions: thy­roid the­rapy, estro­pro­ges­ta­tive birth con­trol pills, pro­ges­to­gens, anti-infammatory agents (incl. glu­co­cor­ti­coids and aspi­rin), anti­de­pres­sants, L-Dopa, bro­moc­rip­tine, neu­ro­lep­tica, anti-hypertensives, antiarrhyth­mics (amio­da­rone), hypo­li­pe­mic agents, IGF-1, soma­tos­ta­tin, etc. 

47. Franklyn JA, Black EG, Bet­te­ridge J, Shep­pard MC. Com­pa­ri­son of second and third gene­ra­tion methods for mea­su­re­ment of serum thy­ro­tro­pin in patients with overt hyperthy­roi­dism, patients recei­ving thy­ro­xine the­rapy, and those with nonthy­roi­dal ill­ness. J Clin Endoc­ri­nol Metab. 1994;78(6):1368 – 71
48. Gow SM, Cald­well G, Toft AD, Seth J, Hus­sey AJ, Swee­ting VM, Bec­kett GJ. Rela­tionship bet­ween pitui­tary and other tar­get organ res­pon­si­ve­ness in hypothy­roid patients recei­ving thy­ro­xine repla­ce­ment. J Clin Endoc­ri­nol Metab. 1987;64(2):364 – 70
49. Cus­tro N, Sca­fidi V Cos­tanzo G, Cor­se­llo FP. Varia­tions in the serum levels of thy­roid hor­mo­nes and TSH after intake of a dose of L-thyroxine in euthy­roid sub­jects and in ade­qua­tely trea­ted hypothy­roid patients. Bull Soc Ital Biol Sper. l989; 65(11):1045 – 52
50. England ML, Hersh­man JM. Serum TSH con­cen­tra­tion as an aid to moni­to­ring com­pliance with thy­roid hor­mone the­rapy in hypothy­roi­dism. Am J Med Sci. 1986 Nov;292(5):264 – 6
51. Cho­pra U, Carl­son HE, Solo­mon DH. Com­pa­ri­son of inhi­bi­tory effects of 3,5,3′-triiodothyronine (T3), thy­ro­xine (T4), 3,3,’,5′-triiodothyronine (rT3,), and 3,3′-diiodothyronine (T2) on thyrotropin-releasing hormone-induced release of thy­ro­tro­pin in the rat in vitro. Endoc­ri­no­logy. 1978; 103(2): 393 – 402
52. Fra­ser WD, Big­gart EM, O’Reilly DS, Gray HW, McKi­llop JH, Thom­son JA. Are bioche­mi­cal tests of thy­roid func­tion of any value in moni­to­ring patients recei­ving thy­ro­xine repla­ce­ment? Br Med J (Clin Res Ed). 1986 Sep 27;293(6550): 293 – 808
53. Coo­per DS, Wal­ker H, Rod­bard D, Maloof F. Periphe­ral res­pon­ses to thy­roid hor­mone before and after L-thyroxine the­rapy in patients with subc­li­ni­cal hypothy­roi­dism. J Clin Endoc­ri­nol Metab. 1981 Dec;53(6):1238 – 42
54. Saberi M, Uti­ger RD. Serum thy­roid hor­mone and thy­ro­tro­pin con­cen­tra­tions during thy­ro­xine and triio­dothy­ro­nine the­rapy. J Clin Endoc­ri­nol Meta­bol. 1974;39:923 – 7
55. Rey Stoc­ker I, Zuf­fe­rey MM, Lemarchand MT, Rais M. The sen­si­bi­lity of the hypophy­sis, the gonads and the thy­roid before and after the admi­nis­tra­tion of oral con­tra­cep­ti­ves. A resume. Pediatr Ann. 1981;10(12):15 – 20.
56. Lemarchand-Beraud T. Influence of estro­gens on pitui­tary res­pon­si­ve­ness to LHRH and TRH in human. Rey­mond M, Berthier C. Ann Endoc­ri­nol Paris. 1977; 38(6): 379 – 82.
57. El-Etreby MF, Graf KJ, Gun­zel P, Neu­mann F. Eva­lua­tion of effects of sexual ste­roids on the hypothalamic-pituitary sys­tem of ani­mals and man. Arch Toxi­col Suppl. 1979;2:11 – 39
58. Prank K, Ranft U, Berg­mann P, Schuer­me­yer T, Hesch RD, von Zur Muh­len A. Cir­ca­dian and pul­sa­tile TSH sec­re­tion under phy­sio­lo­gi­cal and patho­lo­gi­cal con­di­tions. Horm Metab Res Suppl. 1990; 23:12 – 7
59. Re RN, Kou­ri­des IA, Rid­ge­way EC, Wein­traub BD, Maloof F. The effect of glu­co­cor­ti­coid admi­nis­ta­tion on human pitui­tary sec­re­tion of thy­ro­tro­pin and pro­lac­tin. J Clin Endoc­ri­nol Metab. 1976; 43:338 – 46.
60. Atter­will CK, Catto LC, Heal DJ, Holland CW, Dic­kens TA, Jones CA. The effects of desi­pra­mine (DMI) and elec­tro­con­vul­sive shock (ECS) on the func­tion of the hypothalamo-pituitary-thyroid axis in the rat. Psycho­neu­roen­doc­ri­no­logy. 1989;14(5):339 – 46
61. Kap­tein EM, Kletzsky OA, Spen­cer CA, Nico­loffJT. Effects of pro­lon­ged dopa­mine infu­sion on ante­rior pitui­tary func­tion in nor­mal males. J Clin Endoc­ri­nol Metab 1980; 51:488 – 91
62. Samuels MH, Kra­mer P, Wil­son D, Sex­ton F. Effect ofna­lo­xone infu­sions on pul­sa­tile thy­ro­tro­pin sec­re­tion. J Clin Endoc­ri­nol Metab. 1994;78(5):129 – 32.
63. Bur­ger A, Nicod DP, Lemarchaud-Beraud T, Vallot­ton MB. Effect of amio­da­rone on serum triio­dothy­ro­nine, reverse triio­dothy­ro­nine, thy­ro­xine and thy­ro­tro­pin. J Clin Invest 1976; 58: 255 – 9
64. Davis PJ, Davis FB, Uti­ger RD, Kulaga SF Jr. Chan­ges in serum thy­ro­tro­pin (TSH) in man during halo­fe­nate admi­nis­tra­tion. J Clin Endoc­ri­nol Metab 1976; 43(4): 873 – 81
65. Trai­ner PI, Holly 1, Med­bak S, Rais LH, Bes­ser GM. The effect of recom­bi­nant IGF-1 on ante­rior pitui­tary func­tion in healthy volun­teers. Clin Endoc­ri­nol (Chef) 1994; 41(6): 801 – 7. 

Toxic foods: MSG, alcohol

66. Bakke JL, Law­rence N, Ben­nett J, Robin­son S, Bowers CY. Late endoc­rine effects of admi­nis­te­ring mono­so­dium glu­ta­mate to neo­na­tal rats. Neu­roen­doc­ri­no­logy 1978; 26(4): 220 – 8.
67. Gree­ley GH Jr, Nichol­son GF, Kizer JS. A dela­yed LH/FSH rise after gona­dec­tomy and a dela­yed serum TSH rise after thy­roi­dec­tomy in monosodium-L-glutamate (MSG)-treated rats. Brain Res 1980; 195(1):111 – 22.
42. Modi­gliani E, Periac P, Perret G, Hugues JN, Coste T. TRH res­ponse in 53 patients with chro­nic alcoho­lism. Ann Med Interne Paris. 1979; 130(5): 297 – 302

Thy­roid disea­ses: hyperthy­roi­dism, Graves-Basedow disease, nodu­lar goi­ter, thy­roi­di­tis, secon­dary or ter­tiary hypothy­roi­dism, con­ge­ni­tal hypothyroidism

68. Spen­cer CA, Lai-Rosenfeld AO, Gutt­ler RB, LoPresti J, Mar­cus AO, Nima­la­su­riya A, Eigen A, Doss RC, Green BJ, Nico­loff JT. Thy­ro­tro­pin sec­re­tion in thy­ro­to­xic and thyroxine-treated patients: assess­ment by a sen­si­tive immu­noenzy­mo­me­tric assay. J Clin Endoc­ri­nol Metab. 1986 Aug;63(2):349 – 55
69. Yeo PP, Loh KC. Subc­li­ni­cal thy­ro­to­xi­co­sis. Adv Intern Med 1998; 43: 501 – 32
70. Chan­son P. Insuf­fi­sance thy­ro­tro­pic. Rev Prat. 1998 15; 48(18): 2023 – 6
71. Peter­sen PH, Ros­leffF, Ras­mus­sen J, Hobolth N. Stu­dies on the requi­red analy­ti­cal qua­lity of TSH mea­su­re­ments in scree­ning for con­ge­ni­tal hypothy­roi­dism. Scand J Clin Lab Invest Suppl. 1980;155: 5 – 93.
72. Fofa­nova 0V, Taka­mura N, Kinoshita E, Yoshi­moto M, Tsuji Y, Peter­kova VA, Evgra­fov 0V, Dedov II, Goncha­rov NP, Yamashita S. Rarity of PIT1 invol­ve­ment in chil­dren from Rus­sia with com­bi­ned pitui­tary hor­mone defi­ciency. Am J Med Genet 1998; 77(5): 360 – 5.

FACTORS that ELEVATE the serum TSH

Neo­na­tus, stress — emo­tio­nal arou­sal, cold expo­sure, sleep depri­va­tion, adre­nal insuf­fi­ciency, reco­very from severe ill­ness, con­ge­ni­tal malformations

73. Hashi­moto H, Sato F, Kubo M, Ohki T. Matu­ra­tion of the pituitary-thyroid axis during the peri­na­tal period. Endoc­ri­nol Jpn 1991;38(2):151 – 7
74. Gen­drel D, Feins­tein MC, Gre­nier J, Roger M, Ingrand J, Chaus­sain JL, Can­lorbe P, Job JC. Fal­sely ele­va­ted serum thy­ro­tro­pin (TSH) in new­born infants: Trans­fer from mothers to infants of a fac­tor inter­fe­ring in the TSH radioim­mu­noas­say. J Clin Endoc­ri­nol Metab 1981;52(1):62 – 5.
75. Arma­rio A, Lopez Cal­de­ron A, Jolin T, Cas­te­lla­nos JM. Sen­si­ti­vity of ante­rior pitui­tary hor­mo­nes to gra­ded levels of psycho­lo­gi­cal stress. Life Sci 1986; 39(5): 471 – 5
76. Reed HL, Sil­ver­man ED, Sha­kir KM, Dons R, Bur­man KD, O’Brian JT. Chan­ges in serum triio­dothy­ro­nine (TQ kine­tics after pro­lon­ged Antarc­tic resi­dence: The polar T3 syn­drome. J Clin Endoc­ri­nol Metab. 1990; 70(4): 965 – 74
77. Sada­ma­tsu M, Kato N, Iida H, Takahashi S, Sakaue K, Takahashi K, Hashida S, Ishi­kawa E. The 24-hour rhythms in plasma growth hor­mone, pro­lac­tin and thy­roid sti­mu­la­ting hor­mone: effect of sleep depri­va­tion. J Neu­roen­doc­ri­nol. 1995 Aug;7(8):597 – 606
78. Sjo­berg S, Wemer S. Inc­rea­sed level of TSH can be a sign of adre­nal cor­tex fai­lu­res: Net neces­sa­rily of thy­roid gland disease. Lakar­tid­nin­gen 1999; 96(5):464 – 5
79. De Nayer P, Dozin B, Van­de­put Y, Bot­tazzo FC, Crabbe J. Alte­red inte­rac­tion bet­ween triio­dothy­ro­nine and its nuc­lear recep­tors in absence of cor­ti­sol: A pro­po­sed mecha­nism for inc­rea­sed thy­ro­tro­pin sec­re­tion in cor­ti­coid defi­ciency sta­tes. Eur J Clin Invest. 1987 Apr;17(2):106 – 8
80. Oakley GA, Muir T, Ray M, Gird­wood RW, Ken­nedy R, Donald­son MD. Inc­rea­sed inci­dence of con­ge­ni­tal mal­for­ma­tions in chil­dren with tran­sient thyroid-stimulating hor­mo­nal ele­va­tion on neo­na­tal scree­ning. J Pediatr. 1998; 132(4): 573 – 4

Medi­ca­tions: iodine, antithy­roi­dea, , lithium, neu­ro­lep­tica (halo­pe­ri­dol, chlor­pro­ma­zine), cime­ti­dine, sul­fapy­ri­dine, clo­mi­fen, anti­de­pres­sants (ser­tra­line), antihis­ta­mi­nic agents, cho­les­to­grahic agents, etc.

30. Devos P. Ratio­nele keuze van schild­klier­func­tie tests. Tijdschr Geneesk. 1990;46(8):591 – 9
81. Klein­mann RE, Vage­na­kis AG, Bra­ver­man LE. The effect of iopa­noic acid on the regu­la­tion of thy­ro­tro­pin sec­re­tion in euthy­roid sub­jects. J Clin Endoc­ri­nol Metab. 1980;51(2): 399 – 403
82. Mc Caven KC, Gar­ber JR, Spark R. Ele­va­ted serum thy­ro­tro­pin in thyroxine-treated patients with hypothy­roi­dism given ser­tra­line. N Engl J Med. 1997; 337(14):1010 – 1
83. Brown CG, Har­land RE, Major IR, Atter­will CK. Effects of toxic doses of a novel his­ta­mine (H2) anta­go­nist on the rat thy­roid gland. Food Chem Toxi­col. 1987; 25(10):787 – 94

Auto-immune thy­roi­di­tis and hypothy­roi­dism: pri­mary, iodine-deficient, thy­roid hor­mone resistance

30. Devos P. Ratio­nele keuze van schild­klier­func­tie tests. Tijdschr Geneesk. 1990;46(8): 591 – 9
84. Miss­ler U, Gute­kunst R, Wood WG. Thy­ro­glo­bu­lin is a more sen­si­tive indi­ca­tor of iodine defi­ciency than thy­ro­tro­pin: Deve­lop­ment and eva­lua­tion of dry blood spot assays for thy­ro­tro­pin and thy­ro­glo­bu­lin in iodine– defi­cient geo­graphi­cal areas. Eur J Clin Chem Clin Biochem 1994; 32(3): 137 – 43
85. Volpe R. Suba­cute (de Quervain’s) thy­roi­di­tis. J Clin Endoc­ri­nol Metab. 1979 Mar;8(1):81 – 95
86. Mas­soudi MS, Mei­lahn EN, Orchard TJ, Foley TP Jr, Kuller LH, Cos­tan­tino JP, Buhari AM. Thy­roid func­tion and peri­me­no­pau­sal lipid and weight chan­ges: the Thy­roid Study in Healthy Women (TSH-W). J Womens Health. 1997 Oct;6(5):553 – 8
87. Small­ridge RC, Par­ker RA, Wiggs EA, Raja­go­pal KR, Fein HG. Thy­roid hor­mone resis­tance in a large kin­dred: phy­sio­lo­gic, bioche­mi­cal, phar­ma­co­lo­gic, and neu­ropsycho­lo­gic stu­dies. Am J Med. 1989 Mar;86(3):289 – 96
TSH-secreting tumors (rare)
88. Small­ridge RC. Thyrotropin-secreting pitui­tary tumors, Endoc­ri­nol Metab Clin North Am 1987 Sep;16(3):765 – 92

FACTORS that ELEVATE or DEPRESS serum TSH

Phy­sio­lo­gi­cal serum TSH fluctuations

89. Bra­bant G, Prank K, Ranft U, Schuer­me­yer T, Wag­ner TO, Hau­ser H, Kum­mer B, Feist­ner H, Hesch RD, von zur Muh­len A. Phy­sio­lo­gi­cal regu­la­tion of cir­ca­dian and pul­sa­tile thy­ro­tro­pin sec­re­tion in nor­mal man and woman. J Clin Endoc­ri­nol Metab. 1990 Feb;70(2):403 – 9
90. Bra­bant G, Prank K, Ranft U, Berg­mann P, Schuer­me­yer T, Hesch RD, von zur Muh­len A. Cir­ca­dian and pul­sa­tile TSH sec­re­tion under phy­sio­lo­gi­cal and pathophy­sio­lo­gi­cal con­di­tions. Horm Metab Res Suppl. 1990;23:12 – 7
91. Goichot B, Bran­den­ber­ger G, Sch­lien­ger JL. Sec­re­tion of thy­ro­tro­pin during sta­tes of wake­ful­ness and sleep. Phy­sio­lo­gi­cal data and cli­ni­cal appli­ca­tions. Presse Med. 1996;25(21):980 – 4
92. Rao ML, Gross G, Stre­bel B, Hala­ris A, Huber G, Brau­nig P, Mar­ler M. Cir­ca­dian rhythm of tryp­tophan, sero­to­nin, mela­to­nin, and pitui­tary hor­mo­nes in schi­zoph­re­nia. Biol Psychiatry. 1994;1:35(3): 151 – 63
93. Rose SR, Nisula BC. Cir­ca­dian varia­tion of thy­ro­tro­pin in childhood. J Clin Endoc­ri­nol Metab. 1989; 68(6):1086 – 90
94. Scan­lon MF, Weet­man AP, Lewis M, Pour­mand M, Rodri­guez Arnao MD, Weight­man DR, Hall R. Dopa­mi­ner­gic modu­la­tion of cir­ca­dian thy­ro­tro­pin rhythms and thy­roid hor­mone levels in euthy­roid sub­jects. J Clin Endoc­ri­nol Metab. 1980 Dec;51(6):1251 – 6
95. Rom Bugos­lavs­kaia ES, Shcher­ba­kova VS. Sea­so­nal cha­rac­te­ris­tics of the effect of mela­to­nin on thy­roid func­tion. Bull Eksp Biol Med. 1986;101(3):268 – 9

Varia­tions in the bio­lo­gi­cal acti­vity of TSH

96. Beck-Peccoz P, Per­sani L. Varia­ble bio­lo­gi­cal acti­vity of thy­roid sti­mu­la­ting hor­mone. Eur J Endoc­ri­nol. 1994 Oct;131(4):331 – 40
97. Maes M, Mom­men K, Hen­drickx D, Pee­ters D, D’Hondt P, Ran­jan R, De Meyer F, Scharpe S. Com­po­nents of bio­lo­gi­cal varia­tion of TSH, TT3, FT4, PRL, cor­ti­sol and tes­tos­te­rone in healthy volun­teers. Clin Endoc­ri­nol (Oxf). 1997 May;46(5):587 – 98
98. Hiro­moto M, Nishi­kawa M, Ishihara T, Yoshi­kawa N, Yoshi­mura M, Inada M. Bioac­ti­vity of thy­ro­tro­pin (TSH) in patients with cen­tral hypothy­roi­dism: Com­pa­ri­son bet­ween the in vivo 3,5,3′- triiodo-thyronine res­ponse to TSH and in vitro bioac­ti­vity of TSH. J Clin Endoc­ri­nol Metab. 1995 Apr;80(4):1124 – 8

TSH test kit imperfections

99. Ras­mus­sen AK, Hils­ted L, Perrild H, Chris­tian­sen E, Siersbaek-Nielsen K, Feldt-Rasmussen U. Disc­re­pan­cies bet­ween thy­ro­tro­pin (TSH) meaa­su­re­ment by four sen­si­tive immu­no­me­tric assays. Clin Chim Acta. 1997 Mar 18;259(1 – 2):117 – 28
100. Libeer JC, Simo­net L, Gillet R. Analy­ti­cal eva­lua­tion of twenty assays for deter­mi­na­tion of thy­ro­tro­pin (TSH). Ann Biol Clin Paris. 1989; 47(1): 1 – 11
101. Spen­cer CA, Takeuchi M, Kaza­ros­yan M, Mac­Ken­zie F, Bec­kett GJ, Wil­kin­son E. Interlaboratory/intermethod dif­fe­ren­ces in func­tio­nal sen­si­ti­vity of immu­no­me­tric assays of thy­ro­tro­pin (TSH) and impact on relia­bi­lity of mea­su­re­ment of sub­nor­mal con­cen­tra­tions of TSH. Clin Chem. 1995 Mar;41(3):367 – 74
102. Faber J, Gam A, Siers­baek Niel­sen K. Impro­ved sen­si­ti­vity of serum thy­ro­tro­pin mea­su­re­ments: Stu­dies on serum sex hormone-binding glo­bu­lin in patients with redu­ced serum thy­ro­tro­pin. Acta Endoc­ri­nol Copenh 1990; 123(5): 535 – 40
103. Laur­berg P. Per­sis­tent pro­blems with the spe­ci­fi­city of immu­no­me­tric TSH assays. Thy­roid. 1993 Winter;3(4):279 – 83
104. Sch­lien­ger JL, Sapin R, Gru­nen­ber­ger F, Gas­ser F, Pra­dig­nac A. Thy­ro­tro­pin assay by che­mi­lu­mi­nes­cence in the diag­no­sis of dysthy­roi­dism with low thy­ro­tro­pin and nor­mal thy­roid hor­mo­nes levels. Pathol Biol Paris. 1993; 41(5): 463 – 8
105. Spen­cer C, Eigen A, Shen D, Duda M, Qualls S, Weiss S, Nico­loff J. Spe­ci­fi­city of sen­si­tive assays of thy­ro­tro­pin (TSH) used to screen for thy­roid disease in hos­pi­ta­li­zed patients. Clin Chem. 1987 Aug;33(8):1391 – 6
106. Spen­cer CA, Cha­lland GS. Inter­fe­rence in a radioim­mu­noas­say for human thy­ro­tro­pin. Clin Chem 1977;23(3): 584 – 8
107. Kahn BB, Wein­traub BD, Csako G, Zweig MH. Fac­ti­tious ele­va­tion of thy­ro­tro­pin in a new ultra-sensitive assay: Impli­ca­tions for the use of monoc­lo­nal anti­bo­dies in ‘sand­wich’ immuno-assay. J Clin Endoc­ri­nol Metab. 1988 Mar;66(3):526 – 33
108. Kou­ri­des IA, Wein­traub BD, Mar­to­rana MAL, Maloof F. Alpha subu­nit con­ta­mi­na­tion of human albu­min pre­pa­ra­tions: Inter­fe­rence in radioim­mu­noas­say. J Clin Endoc­ri­nol Metab. 1976; 43(4): 919 – 23
109. Bart­lett WA, Brow­ning MC, Jung RT. Arte­fac­tual inc­rease in serum thy­ro­tro­pin con­cen­tra­tion cau­sed by hete­rophi­lic anti­bo­dies with spe­ci­fi­city for IgG of the family Boui­dea. Clin Chem. 1986; 32(12): 22(4 – 9)
110. Csako G, Wein­traub BD, Zweig MH. The potency of immu­no­glo­bu­lin anti­bo­dies in a monoc­lo­nal immu­no­ra­dio­me­tric assay for thy­ro­tro­pin. Clin Chem. 1988 Jul;34(7):1481 – 3
111. Seghers J, Sch­ruers F, De Nayer P, Bec­kers C. Inter­fe­rence in thy­ro­tro­pin (TSH) deter­mi­na­tion: Fal­sely ele­va­ted TSH values in a trans­plan­ted patient. Eur J Nucl Med. 1989; 15(4): 194 – 6
112. Spen­cer C, Eigen A, Shen D, Duda M, Quails S, Weiss S, Nico­loff J. Spe­ci­fi­city of sen­si­tive assays of thy­ro­tro­pin (TSH) used to screen for thy­roid disease in hos­pi­ta­li­zed patients. Clin Chem. 1987;33(8):1391 – 6
113. Ealey PA, Marshall NJ, Ekins RP. Time-related thy­roid sti­mu­la­tion by thy­ro­tro­pin and thyroid-stimulating anti­bo­dies, as mea­su­red by the cytoche­mi­cal sec­tion bioas­say. J Clin Endoc­ri­nol Metab. 1981;52(3): 483 – 7

Beware for ove­rre­liance on thy­roid labo­ra­tory tests

115. Rip­pere V. Bioche­mi­cal vic­tims: False nega­tive diag­no­sis through ove­rre­liance on labo­ra­tory results — a per­so­nal report. Med Hypothe­ses. 1983; 10(2): 113.

Other tests : uri­nary T3 as a com­ple­men­tary test

116. Bai­sier W, Her­toghe J, Eeckhaut W. Thy­roid insuf­fi­ciency Is TSH mea­su­re­ment the only diag­nos­tic tool? J Nutr Envi­ronm Med. 2000; 10(3): 109 – 113.

THYROID TREATMENT DISCUSSIONS:

Does thy­roid treat­ment defi­ni­tely sup­press thy­roid gland?

No, after stop­ping thy­roid medi­ca­tions, the thy­roid axis reco­vers its ini­tial con­di­tion gene­rally in 2 to 3 weeks 

Krug­man LG, Hersh­man JM, Cho­pra IJ, Levine GA, Pekary E, Geff­ner DL, Chua Teco GN. Pat­terns off reco­very of the hypothalamic-pituitary-thyroid axis in patients taken of chro­nic thy­roid the­rapy. J Clin Endoc­ri­nol Metab. 1975 Jul;41(1):70 – 80 (full reco­very­back to ini­tial serum T3, T4, TSH levels is obtai­ned after a mean of 16 to 22 days, even after 28 years of treatment)

Vage­na­kis AG, Bra­ver­man LE, Azizi F, Por­ti­nay GI, Ing­bar SH. Reco­very of pitui­tary thy­ro­tro­pic func­tion after with­dra­wal of pro­lon­ged thyroid-suppression the­rapy. N Engl J Med. 1975 Oct 2;293(14):681 – 4 (“During exo­ge­nous hor­mone admi­nis­tra­tion, 131l uptake was sup­pres­sed, and serum thy­ro­tro­pin con­cen­tra­tions before and after admi­nis­tra­tion of thyrotropin-releasing hor­mone were unde­tec­ta­ble. …. After with­dra­wal of long-term thy­roid hor­mone, dec­rea­sed thy­ro­tro­pin reserve per­sis­ted for two to five weeks. Detec­ta­ble values of serum thy­ro­tro­pin (less than 1.2 muU per milli­li­ter) and a nor­mal 131l uptake usually occu­rred con­cu­rrently in two to three weeks. Serum thy­ro­xine con­cen­tra­tion retur­ned to nor­mal at least four weeks after hor­mone withdrawal.”)

Greer MA. The effect on endo­ge­nous thy­roid acti­vity of fee­ding desic­ca­ted thy­roid to nor­mal human sub­jects. N Engl J Med. 1951 Mar 15;244(11):385 – 90 (“After with­dra­wal of thy­roid the­rapy, thy­roid func­tion retur­ned to nor­mal in most sub­jects within 2 weeks, although a few were depres­sed ofr 6 – 11 weeks. Thy­roid func­tion retur­ned as rapidly in those whose glands had been depres­sed by seve­ral years of thy­roid medi­ca­tion as it did for those whose glands had been depres­sed for only a few days.”)

Mosier HD, DeGo­lia RC. Effect of pro­lon­ged admi­nis­tra­tion of thy­roid hor­mone on thy­roid gland func­tion of euthy­roid chil­dren. J Clin Endoc­ri­nol Metab. 1960 Sep;20:1296 – 301. (“In all of the echil­dren and ado­les­cents inc­lu­ded in this study, thy­roid func­tion retur­ned to nor­mal (as jud­ged by cli­ni­cal signs ans by labo­ra­tory mea­su­re­ments) within four months after dis­con­ti­nuing thy­roid hormone,in spite of pre­vious admi­nis­tra­tion of sup­pres­sive doses for periods of 20 too 125 months during years of soma­tic growth”).

Far­quhar­son RF, Squi­res AH. Inhi­bi­tion of the sec­re­tion of the thy­roid gland by con­ti­nued inges­tion of thy­roid subs­tance. Tr A Am Phy­si­cians. 1941;56:87

Johns­ton MW, Squi­res AH, Far­quhar­son RF. The effect of pro­lon­ged admi­nis­tra­tion of thy­roid. Ann Intern Med. 1951 Nov;35(5):1008 – 22 

Riggs DS, Man EB, Win­kler AW. Serum iodine of euthy­roid sub­jects trea­ted with des­si­ca­ted thy­roid. J Clin Invest. 1945;24:722 – 31

Stein RB, Nico­loff JT. Triio­dothy­ro­nine with­dra­wal test –a test of thyroid-pituitary ade­quacy. J Clin Endoc­ri­nol Metab. 1971 Feb;32(2):127 – 9

If the thy­roid treat­ment is stop­ped because it is jud­ged not neces­sary, reco­very takes place

Rubi­noff H, Fire­man BH. Tes­ting for reco­very of thy­roid func­tion after with­dra­wal of long-term sup­pres­sion the­rapy. J Clin Epi­de­miol. 1989;42(5):417 – 20 (At 8 weeks, 30 of the 45 patients whose chart reviews did not demons­trate a clear need for thy­roid repla­ce­ment., were nor­mal)
Depart­ment of Medi­cine, Kai­ser Per­ma­nente Medi­cal Cen­ter, Oakland, CA 94611.

Mild thy­roid fai­lure: to treat or not to treat 

Argu­ments PRO THYROID USE for mild thy­roid fai­lure

Stu­dies that show the effi­cacy of trea­ting mild thy­roid failure

Little bene­fit of T4 the­rapy if TSH reduc­tions are put into only the range of 3 – 3.5 mU/lL. Mainly stu­dies using dosage titra­tion to TSH levels < 3.0 are asso­cia­ted with impro­ve­ment in symp­toms, lipid abnor­ma­li­ties, and car­dio­vas­cu­lar func­tion (except the study by Meier and collea­gues that sho­wed bene­fit with mini­mal TSH reduc­tions in the 3 – 3.5 mIU/ml range)

21. Meier C, Staub J-J, Roth C-B, Guglie­metti M, Kunz M, Mise­rez AR, Drewe J, Huber P, Her­zog M, Muller B. TSH-controlled L-thyroxine the­rapy redu­ces cho­les­te­rol levels and cli­ni­cal symp­toms in subc­li­ni­cal hypothy­roi­dism. Am J Med. 2001;112:348 – 54
22. Meier C, Staub J-J, Roth C-B, Guglie­metti M, Kunz M, Mise­rez AR, Drewe J, Huber P, Her­zog M, Muller B. TSH-controlled L-thyroxine the­rapy redu­ces cho­les­te­rol levels and cli­ni­cal symp­toms in subc­li­ni­cal hypothy­roi­dism: a dou­ble blind, placebo-controlled trial (Basel Thy­roid Study). J Clin Endoc­ri­nol Metab. 2001; 86:4860 – 6
Coo­per DS 2001 Subc­li­ni­cal hypothy­roi­dism. N Engl J Med 345:260 – 5
Ayala A, War­tofsky L. Mini­mally symp­to­ma­tic (subc­li­ni­cal) hypothy­roi­dism. Endoc­ri­no­lo­gist. 1997;7:44 – 50
20. McDer­mott MT, Ridg­way EC. Cli­ni­cal pers­pec­tive: subc­li­ni­cal hypothy­roi­dism is mild thy­roid fai­lure and should be trea­ted. J Clin Endoc­ri­nol Metab. 2001; 86:4585 – 90 (shows bene­fit with mini­mal TSH reduc­tions down to only the range of 3 – 3.5 mU/liter)

Stu­dies with appro­priate dosage titra­tion to TSH levels under 3.0 are more often asso­cia­ted with impro­ve­ment in symp­toms, lipid abnor­ma­li­ties, and car­dio­vas­cu­lar function

1. Micha­lo­pou­lou G, Ale­vi­zaki M, Pipe­rin­gos G, Mitsi­bou­nas D, Man­tzos E, Adam­pou­los P, Kou­tras DA. High serum cho­les­te­rol levels in per­sons with ‘high-normal’ TSH levels: should one extend the defi­ni­tion of subc­li­ni­cal hypothy­roi­dism. Eur J Endoc­ri­nol. 1998;138:141 – 5
Ayala A, War­tofsky L 2002 The case for more aggres­sive scree­ning and treat­ment of mild thy­roid fai­lure (“subc­li­ni­cal” hypothy­roi­dism). Cle­ve­land Clin J Med 69:313 – 20
37. Faber J, Peter­sen L, Wiin­berg N, Schif­ter S, Mehi­sen J. Hemody­na­mic chan­ges after levothy­ro­xine treat­ment in subc­li­ni­cal hypothy­roi­dism. Thy­roid. 2002; 12:319 – 24
38. Mon­zani F, DiBe­llo V, Carac­cio N, Ber­tini A, Giorgi D, Guisti C, Ferranni E. Effect of levothy­ro­xine on car­diac func­tion and struc­ture in subc­li­ni­cal hypothy­roi­dism: a dou­ble blind, placebo-controlled study. J Clin Endoc­ri­nol Metab. 2001; 86:1110 – 5
39. Biondi B, Fazio S, Pal­mieri EA, Care­lla C, Panza N, Cit­ta­dini A, Bone F, Lom­bardi G, Sacca L. Left ven­tri­cu­lar dias­to­lic dys­func­tion in patients with subc­li­ni­cal hypothy­roi­dism. J Clin Endoc­ri­nol Metab. 1999; 84:2064 – 7
40. Di Bello V, Mon­zani F, Giorgi D, Ber­tini A, Carac­cio N, Valenti G, Talini E, Paterni M, Ferran­nini E, Giusti C. Ultra­so­nic myo­car­dial tex­tu­ral analy­sis in subc­li­ni­cal hypothy­roi­dism. J Am Soc Echo­car­diogr. 2000;13:832 – 40
41. Leka­kis J, Papa­michael C, Ale­vi­zaki M, Pipe­rin­gos G, Mara­fe­lia P, Man­tzos J, Sta­me­te­lo­pou­los S, Kou­tras DA. Flow-mediated, endothelium-dependent vaso­di­la­ta­tion is impai­red in sub­jects with hypothy­roi­dism, bor­der­line hypothy­roi­dism, and high-normal serum thy­ro­tro­pin values. Thy­roid. 1997; 7:411 – 4
42. Tad­dei S, Carac­cio N, Vir­dis A, Dar­dano A, Ver­sari D, Ghia­doni L, Sal­vetti A, Ferran­nini E, Mon­zani F. Impai­red endothelium-dependent vaso­di­la­ta­tion in subc­li­ni­cal hypothy­roi­dism: bene­fi­cial effect of levothy­ro­xine the­rapy. J Clin Endoc­ri­nol Metab. 2003;88:3731 – 7
43. Bak­ker SJ, ter Maa­ten JC, Popp-Snijders C, Slaets JPJ, Heine RJ, Gans ROB. The rela­tionship bet­ween thy­ro­tro­pin and low den­sity lipo­pro­tein cho­les­te­rol is modi­fied by insu­lin sen­si­ti­vity in healthy euthy­roid sub­jects. J Clin Endoc­ri­nol Metab. 86:1206 – 11
44. Krausz Y, Freed­man N, Les­ter H, New­man JP, Bar­kai G, Bocher M, Chi­sin R, Bonne O. Regio­nal cere­bral blood flow in patients with mild hypothy­roi­dism. J Nucl Med. 2004; 45:1712 – 5
45. Imai­zumi M, Akahoshi M, Ichi­maru S, Nakashima E, Hida A, Soda M, Usa T, Ashi­zawa K, Yoka­yama N, Maeda R, Naga­taki S, Eguchi K. Risk for ische­mic heart disease and all-cause mor­ta­lity in subc­li­ni­cal hypothy­roi­dism. J Clin Endoc­ri­nol Metab. 2004;89:3365 – 70
46. Mon­zani F, Carac­cio N, Koza­kowa M, Dar­dano A, Vit­tone F, Vir­dis A, Tad­dei S, Palombo C, Ferran­nini C. Effect of levothy­ro­xine repla­ce­ment on lipid pro­file and intima-media thick­ness in subc­li­ni­cal hypothy­roi­dism: a double-blind, placebo-controlled study. J Clin Endoc­ri­nol Metab. 2004;89:2099 – 106 

Other stu­dies in defence of treat­ment of mild thy­roid fai­lure: it is mpor­tant to treat mild thy­roid fai­lure to avoid adverse phy­si­cal and psycho­lo­gi­cal consequences

19. Mon­zani F, Del Gue­rra P, Carac­cio N, Pru­neti CA, Pucci E, Luisi M, Baschieri L. Subc­li­ni­cal hypothy­roi­dism: neu­ro­beha­vio­ral fea­tu­res and bene­fi­cial effect of L-thyroxine treat­ment. Clin Inves­tig. 1993 May;71(5):367 – 71
Tappy L, Ran­din JP, Sch­wed P, Werthei­mer J, Lemarchand-Beraud T. Pre­va­lence of thy­roid disor­ders in psycho­ge­ria­tric inpa­tients. A pos­si­ble rela­tionship of hypothy­roi­dism with neu­ro­tic depres­sion but not demen­tia. J Am Geriatr Soc. 1987;35:526 – 31
20. Joffe RT, Levitt AJ 1992 Major depres­sion and subc­li­ni­cal (grade 2) hypothy­roi­dism. Psycho­neu­roen­doc­ri­no­logy. 17:215 – 21
21. Hag­gerty Jr JJ, Stern RA, Mason GA, Beck­with J, Morey CE, Prange Jr AJ. Subc­li­ni­cal hypothy­roi­dism: A modi­fia­ble risk fac­tor for depres­sion? Am J Psychiatry. 1993;150:508 – 10
22. Man­ciet G, Dar­ti­gues JF, Decamps A, et al. 1995 The PAQUID sur­vey and corre­la­tes of subc­li­ni­cal hypothy­roi­dism in elderly com­mu­nity resi­dents in the south­west of France. Age Aging. 24:235 – 41
Bal­dini IM, Vita A, Maura MC, Amo­dei V, Carrisi M, Bra­vin S, Can­ta­la­messa L. Psycho­patho­lo­gi­cal and cog­ni­tive fea­tu­res in subc­li­ni­cal hypothy­roi­dism. Prog Neu­ropsychophar­ma­col Biol Psychiatry. 1997 Aug;21(6):925 – 35
23. Gan­guli M, Bur­meis­ter LA, Sea­berg EC, Belle S, DeKosky ST. Asso­cia­tion bet­ween demen­tia and ele­va­ted TSH: a community-based study. Biol Psychiatry. 1996;40:714 – 25
24. Mon­zani F, Carac­cio N, Sici­liano G, Manca L, Murri L, Ferran­nini E. Cli­ni­cal and bioche­mi­cal fea­tu­res of muscle dys­func­tion in subc­li­ni­cal hypothy­roi­dism. J Clin Endoc­ri­nol Metab. 1997;82:3315 – 8
25. Mon­zani F, Carac­cio N, Del Gue­rra P, Caso­laro A, Ferran­nini E. Neu­ro­mus­cu­lar symp­toms and dys­func­tion in subc­li­ni­cal hypothy­roid patients: bene­fi­cial effect of L-T4 repla­ce­ment the­rapy. Clin Endoc­ri­nol. 1999;51:237 – 42
26. Misiu­nas A, Ravera HN, Faraj G, Faure E. Periphe­ral neu­ro­pathy in subc­li­ni­cal hypothy­roi­dism. Thy­roid 1995;5:283 – 6
Gou­lis DG, Tsim­pi­ris N, Dela­rou­dis S, Mal­tas B, Tzoiti M, Dagi­las A, Avra­mi­des A. Sta­pe­dial reflex: a bio­lo­gi­cal index found to be abnor­mal in cli­ni­cal and subc­li­ni­cal hypothy­roi­dism. Thy­roid. 1998 Jul;8(7):583 – 7
Beyer IW, Kar­mali R, DeMeester-Mirkine N, Cogan E, Fuss MJ. Serum crea­tine kinase levels in overt and subc­li­ni­cal hypothy­roi­dism. Thy­roid 1998;8:1029 – 31
Had­dow JE, Palo­maki GE, Allan WC, Williams JR, Knight GJ, Gag­non J, O’Heir CE, Mitchell ML, Her­mos RJ, Wais­bren SE, Faix JD, Klein RZ. Mater­nal thy­roid defi­ciency during preg­nancy and sub­se­quent neu­ropsycho­lo­gi­cal deve­lop­ment of the child. N Engl J Med. 1999 Aug 19;341(8):549 – 55
Foun­da­tion for Blood Research, Scar­bo­rough, ME 04074, USA
Ridg­way EC, Coo­per DS, Wal­ker H, Rod­bard D, Maloof F. Periphe­ral res­pon­ses to thy­roid hor­mone before and after L-thyroxine the­rapy in patients with subc­li­ni­cal hypothy­roi­dism. J Clin Endoc­ri­nol Metab. 1981 Dec;53(6):1238 – 42
27. Coo­per DS, Hal­pern R, Wood LC, Levin AA, Ridg­way EC. L-thyroxine the­rapy in subc­li­ni­cal hypothy­roi­dism. Ann Intern Med. 1984;101:18 – 24
28. Nys­trom E, Cai­dahl K, Fager G, Wik­kelso C, Lund­berg P-A, Linds­tedt G. A double-blind cross-over 12-month study of L-thyroxine treat­ment of women with ’subc­li­ni­cal’ hypothy­roi­dism. Clin Endoc­ri­nol. 1988;29:63 – 76 (Appro­xi­ma­tely one woman in four with this ‘subc­li­ni­cal’ con­di­tion will bene­fit from L-thyroxine treat­ment)
29. Bell GM, Todd WT, For­far JC, Martyn C, Wathen CG, Gow S, Rie­mersma R, Toft AD. End-organ res­pon­ses to thy­ro­xine the­rapy in subc­li­ni­cal hypothy­roi­dism. Clin Endoc­ri­nol (Oxf). 1985 Jan;22(1):83 – 9
For­far JC, Wathen CG, Todd WT, Bell GM, Han­nan WJ, Muir AL, Toft AD. Left ven­tri­cu­lar per­for­mance in subc­li­ni­cal hypothy­roi­dism. Q J Med. 1985 Dec;57(224):857 – 65 Fol­des J, Ist­vanfy M, Hal­magyi M, Varadi A, Gara A, Par­tos O. Hypothy­roi­dism and the heart. Exa­mi­na­tion of left ven­tri­cu­lar func­tion in subc­li­ni­cal hypothy­roi­dism. Acta Med Hung. 1987;44:337 – 47
30. Kahaly GJ 2000 Car­dio­vas­cu­lar and athe­ro­ge­nic aspects of subc­li­ni­cal hypothy­roi­dism. Thy­roid 10:665 – 79
31. Arem R, Rokey R, Kiefe C, Esca­lante DA, Rodri­quez A. Car­diac sys­to­lic and dias­to­lic func­tion at rest and exer­cise in subc­li­ni­cal hypothy­roi­dism: Effect of thy­roid hor­mone the­rapy. Thy­roid. 1996 ;6:397 – 402
32. Mon­zani F, Di Bello V, Carac­cio N, Ber­tini A, Giorgi D, Giusti C, Ferran­nini E. Effect of levothy­ro­xine on car­diac func­tion and struc­ture in subc­li­ni­cal hypothy­roi­dism: a dou­ble blind, placebo-controlled study. J Clin Endoc­ri­nol Metab. 2001 Mar;86(3):1110 – 5
Depart­ment of Inter­nal Medi­cine, Uni­ver­sity of Pisa School of Medi­cine, 56126 Pisa, Italy. fmonzani@med.unipi.it
33. Biondi B, Fazio S, Pal­mieri EA, Care­lla C, Panza N, Cit­ta­dini A, Bone F, Lom­bardi G, Sacca L. Left ven­tri­cu­lar dias­to­lic dys­func­tion in patients with subc­li­ni­cal hypothy­roi­dism. J Clin Endoc­ri­nol Metab. 1999 Jun;84(6):2064 – 7
Depart­ment of Endoc­ri­no­logy of the Uni­ver­sity Fede­rico II, Naples, Italy.
33. Tanis BC, Wes­ten­dorp RGJ, Smelt AHM. Effect of thy­roid subs­ti­tu­tion on hypercho­les­te­ro­lae­mia in patients with subc­li­ni­cal hypothy­roi­dism: a rea­naly­sis of inter­ven­tion stu­dies. Clin Endoc­ri­nol. 1996;44:643 – 9
34. Danese MD, Laden­son PW, Mei­nert CL, Powe NR; Effect of thy­ro­xine the­rapy on serum lipo­pro­teins in patients with mild thy­roid fai­lure: a quan­ti­ta­tive review of the lite­ra­ture. J Clin Endoc­ri­nol Metab. 2000;85:2993 – 3001
35. Micha­lo­pou­lou G, Ale­vi­zaki M, Pipe­rin­gos G, Mitsi­bou­nas D, Man­tzos E, Ada­mo­pou­los P, Kou­tras DA. High serum cho­les­te­rol levels in per­sons with ‘high-normal’ TSH levels: should one extend the defi­ni­tion of subc­li­ni­cal hypothy­roi­dism? Eur J Endoc­ri­nol. 1998 Feb;138(2):141 – 5
36. Bin­dels AJ, Wes­ten­dorp RG, Fro­lich M, Sei­dell JC, Bloks­tra A, Smelt AH. The pre­va­lence of subc­li­ni­cal hypothy­roi­dism at dif­fe­rent total plasma cho­les­te­rol levels in middle aged men and women: a need for case-finding? Clin Endoc­ri­nol. 1999;50:217 – 20
37. Bak­ker SJL, Ter Mat­ten JC, Popp-Snijders C, Slaets JPJ, Heine RJ, Gans ROB. The rela­tionship bet­ween thy­ro­tro­pin and low den­sity lipo­pro­tein cho­les­te­rol is modi­fied by insu­lin sen­si­ti­vity in healthy euthy­roid sub­jects. J Clin Endoc­ri­nol Metab. 2001;86:1206 – 11
38. Leka­kis J, Papa­michael C, Ale­vi­zaki M, Pipe­rin­gos G, Mara­fe­lia P. Flow-mediated, endothelium-dependent vaso­di­la­ta­tion is impai­red in sub­jects with hypothy­roi­dism, bor­der­line hypothy­roi­dism, and high-normal serum thy­ro­tro­pin (TSH) values. Thy­roid. 1997;7:411 – 4
39. Powell J, Zadeh JA, Car­ter G, Greenhalgh RM, Fow­ler PB. Rai­sed serum thy­ro­trophin in women with periphe­ral arte­rial disease. Br J Surg. 1987;74:1139 – 41
Van­der­pump MP, Tun­bridge WM, French JM, Apple­ton D, Bates D, Clark F, Grim­ley Evans J, Rod­gers H, Tun­bridge F, Young ET. The deve­lop­ment of ische­mic heart disease in rela­tion to autoim­mune thy­roid disease in a 20-year follow-up study of an English com­mu­nity. Thy­roid 1996 Jun;6(3):155 – 60
Depart­ment of Medi­cine, New­castle Gene­ral Hos­pi­tal, New­castle upon Tyne, Uni­ted
King­dom.
40. Jaeschke R, Guyatt G, Gers­tein H, Pat­ter­son C, Molloy W, Cook D, Har­per S, Grif­fith L, Car­botte R. Does treat­ment with L-thyroxine influence health sta­tus in middle-aged and older adults with subc­li­ni­cal hypothy­roi­dism? J Gen Intern Med. 1996 Dec;11(12):744 – 9
40. Diek­man T, Lans­berg PJ, Kas­te­lein JJ, Wier­singa WM. Pre­va­lence and correc­tion of hypothy­roi­dism in a large cohort of patients refe­rred for dys­li­pi­de­mia. Arch Intern Med. 1995;155:1490 – 5
41. Perk M, O’Neill BJ. The effect of thy­roid hor­mone the­rapy on angio­graphic coro­nary artery disease pro­gres­sion. Can J Car­diol. 1997;13:273 – 6
42. Stoc­kigt J. Serum thy­ro­tro­pin and thy­roid hor­mone mea­su­re­ments and assess­ment of thy­roid hor­mone trans­port. In: Bra­ver­man LE, Uti­ger RD, eds. Wer­ner and Ingbar’s the thy­roid. 2000, ed 8. Phi­la­delphia: Lip­pen­cott Williams and Wil­kins; 376 – 92
43. Danese MD, Powe NR, Sawin CT, Laden­son PW. Scree­ning for mild thy­roid fai­lure at the perio­dic health exa­mi­na­tion. JAMA. 1996;276:285 – 92
44. McDer­mott MT, Hau­gen BR, Lezotte DC, Seg­gelke S, Ridg­way EC. Mana­ge­ment prac­ti­ces among pri­mary care phy­si­cians and thy­roid spe­cia­lists in the care of hypothy­roid patients. Thy­roid. 2001;11:757 – 76
Zoncu S, Pigliaru F, Putzu C, Pisano L, Var­giu S, Deidda M, Mariotti S, Mer­curo G. Car­diac func­tion in bor­der­line hypothy­roi­dism: a study by pul­sed wave tis­sue Dop­pler ima­ging. Eur J Endoc­ri­nol. 2005 Apr;152(4):527 – 33 (impair­ment of sys­to­lic ejec­tion, a delay in dias­to­lic rela­xa­tio­nand a dec­rease in the com­pliance to the ven­tri­cu­lar filling. Seve­ral sig­ni­fi­cant corre­la­tions were found bet­ween the para­me­ters and serum-free T(3) and T(4) and TSH con­cen­tra­tions. Data strongly sup­port the con­cept of a con­ti­nuum spec­trum of a slight thy­roid fai­lure in autoim­mune thyroiditis)

Subc­li­ni­cal thy­roid dys­func­tion is an abnor­mal serum thyroid-stimulating hor­mone level (refe­rence range: 0.45 to 4.50 µU/mL) and free thy­ro­xine and triio­dothy­ro­nine levels within their refe­rence ranges

Wil­son GR, Curry RW Jr. Subc­li­ni­cal thy­roid disease. Am Fam Phy­si­cian. 2005 Oct 15;72(8):1517 – 24 Depart­ment of Com­mu­nity Health and Family Medi­cine, Uni­ver­sity of Flo­rida Health Science Cen­ter, Jack­son­vi­lle, Flo­rida 32209, USA. george.wilson@jax.ufl.edu

Impor­tant fre­quency of subc­li­ni­cal hypothy­roi­dism:

1. Tun­bridge WM, Eve­red DC, Hall R, Apple­ton D, Bre­wis M, Clark F, Evans JG,
Young E, Bird T, Smith PA. The spec­trum of thy­roid disease in a com­mu­nity: the Whickham sur­vey. Clin Endoc­ri­nol (Oxf). 1977 Dec;7(6):481 – 93
2. Cana­ris GJ, Mano­witz NR, Mayor G, Ridg­way EC. The Colo­rado thy­roid disease pre­va­lence study. Arch Intern Med. 2000;160:526 – 34
3. Hollo­well J, Bra­ver­man LE, Spen­cer CA, Staeh­ling N, Flan­ders D, Han­non H Serum TSH, T4, and thy­roid anti­bo­dies in the Uni­ted Sta­tes popu­la­tion: NHANES III. 72^nd Annual Mee­ting of the Ame­ri­can Thy­roid Asso­cia­tion, Palm Beach, FL, 1999; Abs­tract 213
4. Guel KW, van Sluis­veld IL, Grob­bee DE, Doc­ter R, de Bruyn AM, Hooy­kaas H, van der Merwe JP, van Hemert AM, Kren­ning EP, Hen­ne­mann G, et al. The impor­tance of thy­roid mic­ro­so­mal anti­bo­dies in the deve­lop­ment of ele­va­ted serum TSH in middle-aged women: asso­cia­tions with serum lipids. Clin Endoc­ri­nol (Oxf). 1993 Sep;39(3):275 – 80
5. Rivolta G, Cerutti R, Colombo R, Miano G, Dio­ni­sio P, Grossi E. Pre­va­lence of subc­li­ni­cal hypothy­roi­dism in a popu­la­tion living in the Milan metro­po­li­tan area. J Endoc­ri­nol. Invest. 1999;22:693 – 7
6. Bagchi N, Brown TR, Parish RF. Thy­roid dys­func­tion in adults over age 55 years. A study in an urban U.S. com­mu­nity. Arch Intern Med. 1990;150:785 – 7
7. Sawin CT, Cho­pra D, Azizi F, Man­nix JE, Bacha­rach P. The aging thy­roid. Inc­rea­sed pre­va­lence of ele­va­ted serum thy­ro­tro­pin levels in the elderly. JAMA. 1979;242:247 – 50
8. Lin­de­man RD, Schade DS, LaRue A, Romero LJ, Liang HC, Baum­gart­ner RN, Koeh­ler KM, Garry PJ. Subc­li­ni­cal hypothy­roi­dism in a bieth­nic, urban com­mu­nity. J Am Geriatr Soc. 1999 Jun;47(6):703 – 9
9. Hak AE, Pols HAP, Vis­ser TJ, Drexhage HA, Hof­man A, Wit­te­man JCM. Subc­li­ni­cal hypothy­roi­dism is an inde­pen­dent risk fac­tor for athe­rosc­le­ro­sis and myo­car­dial infarc­tion in elderly women: The Rot­ter­dam study. Ann Intern Med. 2000;132:270 – 8
10. Rosenthal MJ, Hunt WC, Garry PJ, Good­win JS. Thy­roid fai­lure in the elderly: mic­ro­so­mal anti­bo­dies as disc­ri­mi­nant for the­rapy. JAMA. 1987 ;258:209 – 13
Wil­son GR, Curry RW Jr. Subc­li­ni­cal thy­roid disease. Am Fam Phy­si­cian. 2005 Oct 15;72(8):1517 – 24 (The pre­va­lence of subc­li­ni­cal hypothy­roi­dism is about 4 to 8.5 per­cent, and may be as high as 20 per­cent in women older than 60 years)
Depart­ment of Com­mu­nity Health and Family Medi­cine, Uni­ver­sity of Flo­rida Health Science Cen­ter, Jack­son­vi­lle, Flo­rida 32209, USA. george.wilson@jax.ufl.edu 

Impor­tant risk of pro­gres­sion into overt hypothyrodism:

11. Parle JV, Franklyn JA, Cross KW, Jones SC, Shep­pard MC. Pre­va­lence and follow-up of abnor­mal thy­ro­trophin (TSH) con­cen­tra­tions in the elderly in the Uni­ted King­dom. Clin Endoc­ri­nol (Oxf). 1991;34:77 – 83
12. Bas­te­nie PA, Bonnyns M, Vanhaelst L. Natu­ral his­tory of pri­mary myxe­dema. Am J Med. 1985;79:91 – 100
13. Kabadi UM. Subc­li­ni­cal hypothy­roi­dism. Natu­ral course of the syn­drome during a pro­lon­ged follow-up study. Arch Intern Med. 1993;153:957 – 61
Tun­bridge WMG, Bre­wis M, French JM, Apple­ton D, Bird T, Clark F, Eve­red DC, Evans JG, Hall R, Smith P, Stephen­son J, Young E. Natu­ral his­tory of autoim­mune thy­roi­di­tis. Br Med J (Clin Res Ed). 1981 Jan 24;282(6260):258 – 62
14. Van­der­pump MP, Tun­bridge WM, French JM, Apple­ton D, Bates D, Clark F,Grimley Evans J, Hasan DM, Rod­gers H, Tun­bridge F, et al. The inci­dence of thy­roid disor­ders in the com­mu­nity: a twenty-year follow-up of the Whickham Sur­vey. Clin Endoc­ri­nol (Oxf). 1995 Jul;43(1):55 – 68
15. Wang C, Crapo LM. The epi­de­mio­logy of thy­roid disease and impli­ca­tions for scree­ning. Endoc­ri­nol Metab Clin North Am. 1997;26:189 – 218
16. Huber G, Mitrache C, Gugliel­metti M, Huber P, Staub JJ. Pre­dic­tors of overt hypothy­roi­dism and natu­ral course: a long-term follow-up study in impen­ding thy­roid fai­lure. 71^st Annual Mee­ting of the Ame­ri­can Thy­roid Asso­cia­tion, Port­land, OR, 1998; Abs­tract 109 

Impor­tance of cli­ni­cal eva­lua­tion of subc­li­ni­cal hypothyroidism

Zulewski H, Muller B, Exer P, Mise­rez AR, Staub JJ. Esti­ma­tion of tis­sue hypothy­roi­dism by a new cli­ni­cal score: eva­lua­tion of patients with various gra­des of hypothy­roi­dism and con­trols. J Clin Endoc­ri­nol Metab. 1997;82:771 – 6

Stu­dies sho­wing that for other disea­ses such as dia­be­tes and hyper­ten­sion, it is impor­tant to treat mild glan­du­lar failure

54. Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N. Asso­cia­tion of hemo­glo­bin A1C with car­dio­vas­cu­lar disease and mor­ta­lity in adults: the Euro­pean Pros­pec­tive Inves­ti­ga­tion into Can­cer in Nor­folk. Ann Intern Med. 2004;141:413 – 20
55. Vasan RS, Evans JC, Lar­son MG, Wil­son PW, Meigs JB, Rifai N, Ben­ja­min EJ, Levy D. Serum aldos­te­rone and the inci­dence of hyper­ten­sion in nonhy­per­ten­sive per­sons. N Engl J Med. 2004 351:33 – 41
56. Dluhy RG, Williams GH. Aldos­te­rone: villain or bys­tan­der? N Engl J Med. 2004;351:8 – 10

Argu­ments CONTRA THYROID USE for mild thy­roid fai­lure

22. Chu JW, Crapo LM. Should mild hypothy­roi­dism be trea­ted? Am J Med. 2002;112:422 – 3
23. Chu JW, Crapo LM. The treat­ment of subc­li­ni­cal hypothy­roi­dism is sel­dom neces­sary. J Clin Endoc­ri­nol Metab. 2001;86:4591 – 9

Ini­tia­tion of levothy­ro­xine the­rapy for mild thy­roid fai­lure would be inap­pro­priate because it results in over­treat­ment with atten­dant risks of subc­li­ni­cal hyperthy­roi­dism.
(Cri­tic: this risk applies to a very small frac­tion of the popu­la­tion to be trea­ted. An equi­va­lent risk of under­treat­ment of such indi­vi­duals applies as well. Both results could be mini­mi­zed by edu­ca­tion of our pri­mary care phy­si­cians about the desi­ra­ble TSH tar­get in their patients)

1. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hersh­man JM, Bur­man KD, Denke MA, Gor­man C, Coo­per RS, Weiss­man NJ. Subc­li­ni­cal thy­roid disease: scien­ti­fic review and gui­de­li­nes for diag­no­sis and mana­ge­ment. JAMA. 2004;291:228 – 38
3. Surks MI. Com­men­tary: subc­li­ni­cal thy­roid dys­func­tion: a joint sta­te­ment on mana­ge­ment from the Ame­ri­can Asso­cia­tion of Cli­ni­cal Endoc­ri­no­lo­gists, the Ame­ri­can Thy­roid Asso­cia­tion, and The Endoc­rine Society. J Clin Endoc­ri­nol Metab. 2005;90:586 – 7 

T4 in cli­ni­cally hypothy­roid patients but nor­mal tests: does not improve

Pollock MA, Stu­rrock A, Marshall K, David­son KM, Kelly CJ, McMahon AD, McLa­ren EH. Thy­ro­xine treat­ment in patients with symp­toms of hypothy­roi­dism but thy­roid func­tion tests within the refe­rence range: ran­do­mi­sed dou­ble blind pla­cebo con­tro­lled cros­so­ver trial. BMJ. 2001 Oct 20;323(7318):891 – 5

T4 treat­ment in subc­li­ni­cally hypothy­roid patients but nor­mal tests: does not improve the patient (expla­na­tion: The absence of cli­ni­cally rele­vant bene­fits of thy­roid the­rapy for mild thy­roid fai­lure may be due to (1) aTSH nor­ma­li­za­tion that was typi­cally desc­ri­bed as lowe­ring of TSH to < 5 mU/liter, whe­reas levels bet­ween 3 — 5 mU are pro­bably still ele­va­ted and request higher dosage; (2) the use of thy­ro­xine without any addi­tion of triiodothyronine) 

19. Kong WM, Sheikh MH, Lumb PJ, Naou­mova RP, Freed­man DB, Crook M, Dore CJ, Finer N. A 6-month ran­do­mi­zed trial of thy­ro­xine treat­ment in women with mild subc­li­ni­cal hypothy­roi­dism. Am J Med. 2002;112:348 – 54 

Thy­ro­xine treat­ment does improve cho­les­te­rol levels and cli­ni­cal symp­toms in subc­li­ni­cal hypothyroidism 

20. Meier C, Staub J-J, Roth C-B, Guglie­metti M, Kunz M, Mise­rez AR, Drewe J, Huber P, Her­zog M, Muller B. TSH-controlled L-thyroxine the­rapy redu­ces cho­les­te­rol levels and cli­ni­cal symp­toms in subc­li­ni­cal hypothy­roi­dism: a dou­ble blind, placebo-controlled trial (Basel Thy­roid Study). J Clin Endoc­ri­nol Metab. 2001 Oct;86:4860 – 6 (An impor­tant risk reduc­tion of car­dio­vas­cu­lar mor­ta­lity of 9 – 31% can be esti­ma­ted from the obser­ved impro­ve­ment in LDL cholesterol)

Stu­dies that show the impor­tance of trea­ting mild thy­roid excess

Subc­li­ni­cal hyperthy­roi­dism: There is an equal con­cern about appro­priate diag­no­sis and treat­ment of patients with TSH levels that are slightly below the refe­rence inter­val because of risks to both heart and bone 

21. Parle JV, Mai­son­neuve P, Shep­pare MC, Boyle P, Franklyn JA. Pre­dic­tion of all-cause and car­dio­vas­cu­lar mor­ta­lity in elderly peo­ple from one low serum thy­ro­tro­pin result: a 10-year cohort study. Lan­cet. 2001;358:861 – 5
52. Sawin CT, Geller A, Wolf PA, Belan­ger AJ, Baker E, Bacha­rach P, Wil­son PW, Ben­ja­min EJ, D’Agostino RB. Low serum thy­ro­tro­pin con­cen­tra­tions as a risk fac­tor for atrial fibri­lla­tion in older per­sons. N Engl J Med. 1994;331:1249 – 52
53. Statha­tos N, War­tofsky L. Effects of thy­roid hor­mone on bone. Clin Rev Bone Miner Metab. 2004;2:135 – 50 

Con­tro­versy on the best thy­roid treat­ment: T4 or T4-T3?

PRO T4 alone:

Gui­de­li­nes on T4 recommendation

Brent GA, Lar­sen PR. Treat­ment of hypothy­roi­dism. In: Bra­ver­man LE, Uti­ger RD, ed. Wer­ner and Ingbar’s. The Thy­roid: A Fun­da­men­tal and Cli­ni­cal Text. 7^th ed., 1996, Phi­la­delphia, Ravens– Lip­pin­cott Publishers
Uti­ger RD. Hypothy­roi­dism. In DeGroot LJ et al, eds. Endoc­ri­no­logy, Vol 1. 2^nd ed. Phi­la­delphia, Pa: WB Saun­ders Co, 1989;702 – 21
Man­del SJ, Brent GA, Lar­sen PR. Levothy­ro­xine the­rapy in patients with thy­roid disease. Ann Intern Med 1993;119:492 – 502
Roti E, Bra­ver­man LE. Thy­roid hor­mone the­rapy: when to use it, when to avoid it. Drug The­rapy. 1994; 24(4):2 – 35.

T4 and T3– work as good as T4 alone, but not better 

Rodri­guez T, Lavis VR, Mei­nin­ger JC, Kapa­dia AS, Staf­ford LF. Subs­ti­tu­tion of liothy­ro­nine at a 1:5 ratio for a por­tion of levothy­ro­xine: effect on fati­gue, symp­toms of depres­sion, and wor­king memory ver­sus treat­ment with levothy­ro­xine alone. Endocr Pract. 2005 Jul-Aug;11(4):223 – 33
Sawka AM, Gers­tein HC, Marriott MJ, Mac­Queen GM, Joffe RT. Does a com­bi­na­tion regi­men of thy­ro­xine (T4) and 3,5,3′-triiodothyronine improve depres­sive symp­toms bet­ter than T4 alone in patients with hypothy­roi­dism? Results of a double-blind, ran­do­mi­zed, con­tro­lled trial. J Clin Endoc­ri­nol Metab. 2003 Oct;88(10):4551 – 5

T3-T4 (and T3) work bet­ter than T4

Sara­va­nan P, Sim­mons DJ, Green­wood R, Peters TJ, Dayan CM. Par­tial subs­ti­tu­tion of thy­ro­xine (T4) with tri-iodothyronine in patients on T4 repla­ce­ment the­rapy: results of a large community-based ran­do­mi­zed con­tro­lled trial. Clin Endoc­ri­nol Metab. 2005 Feb;90(2):805 – 12
1032. Klop­pen­burg M, Dijk­mans BA, Ras­ker JJ. Effect of the­rapy for thy­roid dys­func­tion on mus­cu­los­ke­le­tal symp­toms. Clin Rheu­ma­tol. 1993 Sep;12(3):341 – 5
45. Her­toghe T, Lo Cas­cio A., Her­toghe J. Con­si­de­ra­ble impro­ve­ment of hypothy­roid symp­toms with two com­bi­ned T3-T4 medi­ca­tion in patients still symp­to­ma­tic with thy­ro­xine treat­ment alone. Anti-Aging Medi­cine, Ed. Ger­man Society of Anti-Aging Medicine-Verlag 2003– 2004; 32 – 43
76. Pareira VG, Haron ES, Lima-Neto N, Medeiros-Neto GA. Mana­ge­ment of myxe­dema coma: report on three suc­cess­fully trea­ted cases with naso­gas­tric or intra­ve­nous admi­nis­tra­tion of triio­dothy­ro­nine. J Endoc­ri­nol Invest. 1982;5:331 – 4
77. Cher­now B, Bur­man KD, John­son DL, McGuire RA, O’Brian JT, War­tofsky L, Geor­ges LP. T3 may be a bet­ter agent than T4 in the cri­ti­cally ill hypothy­roid patient: eva­lua­tion of trans­port across the blood-brain barrier in a pri­mate model. Crit Care Med. 1983 Feb;11(2):99 – 104
78. Arlot S, Debussche X, Lalau JD, Mes­mac­que A, Tolani M, Quichaud J, Four­nier A. Myxoe­dema coma: res­ponse of thy­roid hor­mo­nes with oral and intra­ve­nous high-dose L-thyroxine treat­ment. Inten­sive Care Med. 1991;17(1):16 – 8
Ser­vice de Mede­cine Interne-Endocrinologie, Cen­tre Hos­pi­ta­lier Regio­nal, France

T3-T4 treat­ment: adding T3 to T4 results in more impro­ve­ment of cli­ni­cal symp­toms and signs of hypothy­roi­dism in patients

Bene­vi­cius R, Kaza­na­vi­cius G, Zalin­ko­vi­cius R, Prange AJ. Effects of thy­ro­xine as com­pa­red with thy­ro­xine plus triio­dothy­ro­nine in patients with hypothy­roi­dism. N Engl J Med.1999; 340: 424 – 9. 

When T3 and T4 are both sup­ple­men­ted to the food simul­ta­neously with goi­tro­gens, a much bet­ter pre­ven­tion of goi­ter is obtai­ned than when solely T4 at even 7 times higher con­cen­tra­tion is added 

Dev­lin WF, Wata­nabe H. Thyroxin-triiodothyronine con­cen­tra­tions in thr­yoid pow­ders. J Pharm Sci. 1966 Apr;55(4):390 – 3

In humans, T4-T3 treat­ments reduce serum cho­les­te­rol and inc­rease the speed of the Achi­lles ten­don refle­xes more than T4 treat­ments alone

Alley RA, Danowski TS, Rob­bins T JL, Weir TF, Sabeh G, and Moses CL. Indi­ces during admi­nis­tra­tion of T4 and T3 to euthy­roid adults. Meta­bo­lism. 1968;17(2):97 – 104

A study in rats ren­de­red hypothy­roid shows that cellu­lar euthy­roi­dism is only obtai­ned in the tar­get organs of hypothy­roid rats if T3 is added to the clas­sic T4 medication

Escobar-Morreale HF, del Rey FE, Obre­gon MJ, de Esco­bar GM. Only the com­bi­ned treat­ment with thy­ro­xine and triio­dothy­ro­nine ensu­res euthy­roi­dism in all tis­sues of the thy­roi­dec­to­mi­zed rat. Endoc­ri­no­logy. 1996 Jun;137(6):2490 – 502
Escobar-Morreale HF, Obre­gon MJ, Esco­bar del Rey F, Morreale de Esco­bar G. Repla­ce­ment the­rapy for hypothy­roi­dism with thy­ro­xine alone does not ensure euthy­roi­dism in all tis­sues, as stu­died in thy­roi­dec­to­mi­zed rats. J Clin Invest. 1995 Dec;96(6):2828 – 38

Medi­ca­tions with T4 alone do not suc­ceed in achie­ving com­plete cellu­lar euthy­roi­dism in the tar­get organs, pro­bably because T3 is really the active hor­mone

Asper SP Jr, Selen­kow HA, and Pla­mon­don CA. A com­pa­rai­son of the meta­bo­lic acti­vi­ties of 3,5,3’-triiodothyronine and l-thyroxine in myxe­dema. Bull John Hop­kins Hosp. 1953; 93: 164
Black­burn CM, McCo­nahey WM, Kea­ting FR Jr, Albert A. Calo­ri­ge­nic effects of sin­gle intra­ve­nous doses of l-triiodothyronine and l-thyroxine in myxe­de­ma­tous per­sons. J Clin Invest. 1954 Jun;33(6):819 – 24

T3 is much more potent than T4

Gross J, Pitt-Rivers R. Phy­sio­lo­gi­cal acti­vity of 3:5:3′-L-triiodothyronine. Lan­cet. 1952 Mar 22;1(12):593 – 4
Gross J, Pitt-Rivers R. 3:5:3′-triiodothyronine. 2. Phy­sio­lo­gi­cal acti­vity. Biochem J. 1953 Mar;53(4):652 – 7

Con­di­tions that reduce the con­ver­sion of T4 to T3 such as aging, obe­sity, disease, stress, exer­cise, mal­nu­tri­tion, etc.

Burroughs V, Shenk­man L. Thy­roid func­tion in the elderly. Am J Med Sci. 1982, 283 (1): 8 – 17
Car­ter JN, East­man CJ, Cor­co­ran JM, and Laza­rus L. Inhi­bi­tion of con­ver­sion of thy­ro­xine to triio­dothy­ro­nine in patients with severe chro­nic ill­ness. Clin Endoc­ri­nol. 1976; 5: 587 – 94
Tulp OL and McKee TD Sr. Triio­dothy­ro­nine neo­ge­ne­sis in lean and obese LA/N-cp rats. Biochem Biophys Res Com­mu­ni­ca­tions. 1986; 140 (1): 134 – 42
Katzeff HI, Sel­grad C. Impai­red periphe­ral thy­roid hor­mone meta­bo­lism in gene­tic obe­sity. Endoc­ri­no­logy. 1993; 132 (3): 989 – 95
Crox­son MS and Ibber­tson HK. Low serum triio­dothy­ro­nine (T3) and hypothy­roi­dism in ano­re­xia ner­vosa. J Clin Endoc­ri­nol Metab. 1977; 44: 167 – 73
Harns ARC, Fang SH, Vage­na­kis AG, and Bra­ver­man LE. Effect of star­va­tion, nutri­ment repla­ce­ment, and hypothy­roi­dism on in vitro hepa­tic T4 to T3 con­ver­sion in the rat. Meta­bo­lism. 1978;27(11):1680 – 90
Ops­tad PK, Falch D, Ökte­da­len O, Fon­num F, and Wer­ge­land R. The thy­roid func­tion in young men during pro­lon­ged phy­si­cal exer­cise and the effect of energy and sleep depri­va­tion. Clin Endoc­ri­nol. 1984; 20: 657 – 69
Wal­fish PG. Triio­dothy­ro­nine and thy­ro­xine inte­rre­la­tionships in health and disease. Can Med Ass. J 1976, 115: 338 – 42

Toxic subs­tan­ces such as phe­nols, cad­mium, mer­cury, etc, and medi­ca­tions such as pro­pra­no­lol, amio­da­rone and seve­ral others may inter­fere by sti­mu­la­ting or inhi­bi­ting the T4 to T3 conversion 

Feyes D, Hen­ne­mann G and Vis­ser TJ. Inhi­bi­tion of iodothy­ro­nine deio­di­nase by phe­nolph­ta­lein dyes. Fed Eur Bio­med Sci. 1982; 137(1):40 – 4
Bahn AK, Mills JL, Sny­der PJ, Gann PH, Hou­ten L, Bia­lik O, Holl­mann L, and Uti­ger RD. Hypothy­roi­dism in wor­kers expo­sed to poly­bro­mi­na­ted biphenyls. N Engl J Med. 1980; 302: 31 – 3
Ikeda T, Ito Y, Mura­kami I, Mokuda O, Tomi­naga M and Mashiba H. Con­ver­sion of T4 to T3 in per­fu­sed liver of rats with carbontetrachloride-induced liver injury. Acta Endoc­ri­nol. 1986;112: 89 – 92
Paier B, Hagmü­ller K, Nolli Mi, Gon­za­lez Pon­dal M, Stie­gler C and Zani­no­vich AA. Chan­ges indu­ced by cad­mium admi­nis­tra­tion on thy­ro­xine deio­di­na­tion and sulfhydryl groups in rat liver. J Endoc­ri­nol. 1993; 138: 219 – 24
Barregärd L, Linds­tedt G, Schütz A, Sälls­ten G. Endoc­rine func­tion in mer­cury expo­sed chlo­ral­kali wor­kers. Occup Envir Med. 1994; 51: 536 – 40 

Defi­cien­cies in hor­mo­nes (T3 itself, TSH, growth hor­mone, insu­lin, mela­to­nin, etc) and trace ele­ments (sele­nium, iron, zinc, cup­per, etc) par­tially block this essen­tial step for thy­roid function

Bur­ger AG, Lam­bert M, Cullen M. Interfé­rence de subs­tan­ces médi­ca­men­teu­ses dans la con­ver­sion de T4 en T3 et rT3 chez l’homme. Ann Endoc­ri­nol (Paris). 1981,42:461 – 9
Grus­sen­dorf M, Hüf­ner M. Induc­tion of the thy­ro­xine to triio­dothy­ro­nine con­ver­ting enzyme in rat liver by thy­roid hor­mo­nes and ana­logs. Clin Chim Acta. 1977;80:61 – 6
Erick­son VJ, Cava­lieri RR, Rosen­berg LL. Thyroxine-5’-diodinase of rat thy­roid, but not that of liver, is depen­dent on thy­ro­tro­pin. Endoc­ri­no­logy. 1982;111:434 – 40
Rez­vani I, DiGeorge AM, Dowshen SA, Bour­dony CJ. Action of human growth hor­mone on extrathy­roi­dal con­ver­sion of thy­ro­xine to triio­dothy­ro­nine in chil­dren with hypo­pi­tui­ta­rism. Pediatr Res. 1981;15:6 – 9
Schröder-Van der elst JP, Van der heide D. Effects of streptozocin-induced dia­be­tes and food res­tric­tion on quan­ti­ties and source of T4 and T3 in rat tis­sues. Dia­be­tes. 1992;41:147 – 52
Gavin LA, Mahon FA, Moe­ller M. The mecha­nism of impai­red T3 pro­duc­tion from T4 in dia­be­tes. Dia­be­tes. 1981;30:694 – 9
Hoo­ver PA, Vaughan MK, Little JC, Rei­ter RJ. N-methyl-D-aspartate does not pre­vent effects of mela­to­nin on the repro­duc­tive and thy­roid axes of male Syrian hams­ters. J Endoc­ri­no­logy. 1992;133:51 – 8
Cha­noine J-P, Safran M, Far­well AP, Tran­ter P, Eken­bar­ger DM, Dubord S, Alex s, Arthur JR, Bec­kett GJ, Bra­ver­man LE, Leo­nard JL. Sele­nium defi­ciency and type II 5’-deiodinase regu­la­tion in the euthy­roid and hypothy­roid rat: evi­dence of a direct effect of thy­ro­xine. Endoc­ri­no­logy. 1992;130:479 – 84
Arthur JR, Nicol F, Bec­kett GJ. Sele­nium defi­ciency, thy­roid hor­mone meta­bo­lism, and thy­roid hor­mone deio­di­na­ses. Am J Clin Nutr Suppl. 1993; 57:236S-9S
Beard J, Tobin B, and Green W. Evi­dence for thy­roid hor­mone defi­ciency in iron-deficient ane­mic rats. J Nutr. 1989;772 – 8
Fuji­moto S, Indo Y, Higashi A, Matsuda I, Kashi­wa­bara N, and Nakashima I. Con­ver­sion of thy­ro­xine into triio­dothy­ro­nine in zinc defi­cient rat liver. J Pediatr Gas­troen­te­rol Nutr. 1986;5:799 – 805
Olin KI, Wal­ter RM, and Keen CL. Cop­per defi­ciency affects sele­no­glu­tathione pero­xi­dase and sele­no­deio­di­nase acti­vi­ties and antio­xi­dant defense in wean­ling rats. Am J Clin Nutr 1994;59:654 – 8
West­gren U, Ahren B, Bur­ger A, Inge­mans­son S, Melan­der A. Effects of dexa­metha­sone, desoxy­cor­ti­cos­te­rone, and ACTH on serum con­cen­tra­tions ot thy­ro­xine, 3,5,3’-triiodothyronine and 3,3’,5’-triiodothyronine. Acta Med Scand. 1977;202 (1 – 2): 89 – 92
On the other hand, exces­ses in hor­mo­nes (glucocorticoids36,37, ACTH36, estrogens37,…) and trace ele­ments (iodine38, lithium39, …) may slow down this con­ver­sion.
Heyma P, Lar­kins RG. Glu­co­cor­ti­coids dec­rease the con­ver­sion of thy­ro­xine into 3,5,3’-triiodothyronine by iso­la­ted rat renal tubu­les. Clin Science. 1982; 62: 215 – 20
Scam­mell JG, Shi­ve­rick KT, Fregly MJ. Effect of chro­nic treat­ment with estro­gen and thy­ro­xine, alone and com­bi­ned, on the rate of deio­di­na­tion of l-thyroxine to 3,5,3’-triiodothyronine in vitro. Phar­ma­co­logy. 1986;33: 52 – 7
Aizawa T, Yamada T. Effects of thy­roid hor­mo­nes, antithy­roid drugs and iodide on in vitro con­ver­sion of thy­ro­xine to triio­dothy­ro­nine. Clin Exp Phar­ma­col Phy­siol. 1981; 8: 215 – 25
Voss C, Sch­ro­ber HC, Hart­mann N. Ein­fluss von Lithium auf die in vitro-Deioderung von l-Thyroxin in der Rat­ten leber. Acta Biol Med Germ. 1977; 36:1061 – 5
The absorp­tion of oral T4 can be varia­ble (50 to 73%40,41), con­tras­ting with that of T3 that is more cons­tant and effi­cient (95%)
Hays MT. Absorp­tion of oral thy­ro­xine in man. J Clin Endoc­ri­nol Metab. 1968; 28 (6):749 – 56
Surks MI, Schod­low AR, Stock Jm, Oppenhei­mer JH. Deter­mi­na­tion of iodothy­ro­nine absorp­tion and con­ver­sion of L-thyroxine using tur­no­ver rate tech­ni­ques. J Clin Invest. 1973; 52:809 – 11
Hays MT. Absorp­tion of trii­dothy­ro­nine in man. J Clin Endoc­ri­nol Metab. 1970; 30(5):675 – 6

Defects in the com­mer­cial T4 pre­pa­ra­tion 43,44

Hub­bard WK. FDA notice regar­ding levothy­ro­xine sodium. Fede­ral regis­ter. 1997; 62(157): 1 – 10
Peran S, Garriga MJ, Morreale de Esco­bar G, Asun­cion M, Peran M. Inc­rease in plasma thy­ro­tro­pin levels in hypothy­roid patients during treat­ment due to a defect in the com­mer­cial pre­pa­ra­tion . J Clin Endoc­ri­nol Metab. 1997;82(10):3192 – 5

Thy­roid and the Heart

Claim: Thy­roid hor­mone treat­ment is dan­ge­rous for the heart as it can cause side effects such as atrial fibri­lla­tion.
Facts: Euthy­roi­dism (nor­mal thy­roid func­tion) is essen­tial for the heart; both hypothy­roi­dism as well as hyperthy­roi­dism impair the wor­king of the heart and may faci­li­tate atrial fibrillation.

CONTRA thy­roid use:

Hyperthy­roi­dism: cau­ses tachy­car­dia (cri­tic: tachy­car­dia is the result of hyperthy­roi­dism, hypo­cor­ti­cism, or drin­king of caf­fei­na­ted beve­ra­ges; avoi­ding these con­di­tions by ade­quate treat­ment or abs­ten­tion will gene­rally pre­vent tachycardia)

Maciel BC, Gallo L Jr, Marin Neto JA, Maciel LM, Alves ML, Pac­cola GM, Iazigi N. The role of the auto­no­mic ner­vous sys­tem in the res­ting tachy­car­dia of human hyperthy­roi­dism. Clin Sci (Lond). 1987 Feb;72(2):239 – 44
Aba­die E, Lec­lercq JF, Fisch A, Baba­lis D, Blanche PM, Passa P, Cou­mel P. Patho­ge­ne­sis of tachy­car­dia in hyperthy­roi­dism. Value of Hol­ter moni­to­ring and the use of a beta-blocker. Presse Med. 1985 Feb 2;14(4):197 – 9

Hyperthy­roi­dism (high serum thy­roid hor­mo­nes) is asso­cia­ted with an inc­rea­sed risk of atrial fibrillation

Par­mar MS. Thy­ro­to­xic atrial fibri­lla­tion. Med Gen Med. 2005 Jan 4;7(1):74 (atrial fibri­lla­tion was seen in 15 % of hyperthy­roid patients)
Northern Onta­rio School of Medi­cine, Lau­ren­tian Uni­ver­sity, Sud­bury, Canada
Dorr M, Volzke H. Car­dio­vas­cu­lar mor­bi­dity and mor­ta­lity in thy­roid dys­func­tion. Minerva Endoc­ri­nol. 2005 Dec;30(4):199 – 216 (5.2 times more risk of atrial fibri­lla­tion in hyperthy­roi­dism)
Depart­ment of Inter­nal Medi­cine B, Ernst-Moritz-Arndt-University, Greifs­wald, Ger­many
Frost L, Ves­ter­gaard P, Mose­kilde L. Hyperthy­roi­dism and risk of atrial fibri­lla­tion or flut­ter: a population-based study. Arch Intern Med. 2004 Aug 9 – 23;164(15):1675 (atrial fibri­lla­tion was obser­ved in 8.3 % of hyperthy­roid patients)
Arhus Uni­ver­si­tetshos­pi­tal, Arhus Sygehus, Medicinsk-kardiologisk Afde­ling A. lars.frost@as.aaa.dk

Hyperthy­roi­dism is asso­cia­ted with an inc­rea­sed risk of angina pectoris

Git­lin MJ. L-triiodothyronine-precipitated angina and cli­ni­cal res­ponse. Biol Psychiatry. 1986 May;21(5 – 6):543 – 5

Pos­si­bi­lity to give a beta­bloc­ker together with thy­roid medi­ca­tion to hypothy­roid patients with angina pectoris

Ell­yin F, Fuh CY, Singh SP, Kumar Y. Hypothy­roi­dism with angina pec­to­ris. A cli­ni­cal dilemma. Post­grad Med. 1986 May 15;79(7):93 – 8

A high serum free & total T3 in patients aged 40years or older at emer­gency admis­sion: inc­rea­sed risk of of angina pec­to­ris and myco­car­dial infarct at admis­sion & 3 yrs later (cri­tic: pos­sibly due to hypocorticism??)

Peters A, Ehlers M, Blank B, Exler D, Falk C, Kohl­mann T, Fruehwald-Schultes B, Wellhoe­ner P, Ker­ner W, Fehm HL. Excess triio­dothy­ro­nine as a risk fac­tor of coro­nary events. Arch Intern Med. 2000 Jul 10;160(13):1993 – 9

A high serum T4 can be found in patients with coro­nary heart disease (critic:probably with at the same time a low serum T3, which reflects a cli­ni­cal more hypothy­roid state, because of the dec­rease in con­ver­sion of T4 to T3 that is gene­rally obser­ved in the disease state)

Sido­renko BA, Beglia­rov MI, Titov VN, Masenko VP, Parkhi­mo­vich RM. Blood thy­roid hor­mo­nes in ische­mic heart disease (a com­pa­ri­son with coro­nary angio­graphic data, seve­rity of ste­no­car­dia and blood lipid level)] Kar­dio­lo­giia. 1981 Dec;21(12):96 – 101
Seli­vo­nenko VG, Zaika IV. The func­tion of the thy­roid and thy­ro­tro­pic func­tion in patients with chro­nic ische­mic heart disease and rhythm disor­ders. Lik Sprava. 1998 Jan-Feb;(1):81 – 3

PRO thy­roid use: the heart needs to have thy­roid hor­mo­nes or heart disease appears

Thy­roid hor­mone levels:

Thy­roid hor­mone levels are posi­ti­vely corre­la­ted with the heart rhythm

Tseng KH, Wal­fish PG, Per­saud JA, Gil­bert BW. Con­cu­rrent aor­tic and mitral valve echo­car­dio­graphy per­mits mea­su­re­ment of sys­to­lic time inter­vals as an index of periphe­ral tis­sue thy­roid func­tio­nal sta­tus. J Clin Endoc­ri­nol Metab. 1989 Sep;69(3):633 – 8 

Lower serum T3 (and higher serum T4) is found in heart patients with arrhythmia

Seli­vo­nenko VG, Zaika IV. The func­tion of the thy­roid and thy­ro­tro­pic func­tion in patients with chro­nic ische­mic heart disease and rhythm disor­ders. Lik Sprava. 1998 Jan-Feb;(1):81 – 3
Inama G, Fur­la­ne­llo F, Fio­ren­tini F, Braito G, Ver­gara G, Casana P. Arrhyth­mo­ge­nic impli­ca­tions of non-iatrogenic thy­roid dys­func­tion. G Ital Car­diol. 1989 Apr;19(4):303 – 10 (Hypothy­roi­dism in patients with hyper­ki­ne­tic ven­tri­cu­lar arrhyth­mias (25%), atrial fibri­lla­tion (37.5%) and atrio-ventricular block (37.5%))
Ospe­dale S. Chiara, Trento
Vanin LN, Smet­nev AS, Soko­lov SF, Kotova GA, Masenko VP. Thy­roid func­tion in patients with ven­tri­cu­lar arrhyth­mia. Kar­dio­lo­giia. 1989 Feb;29(2):64 – 7 (Hyperthy­roi­dism was diag­no­sed in 4.8% of 21 patients with per­sis­tent ven­tri­cu­lar arrhyth­mias, and latent hypothy­roi­dism was diag­no­sed in 38.1%)
Vanin LN, Smet­nev AS, Soko­lov SF, Kotova GA, Masenko VP. Study of thy­roid func­tion in patients with paroxys­mal supra­ven­tri­cu­lar tachy­car­dia. Kar­dio­lo­giia. 1989 Jan;29(1):71 – 4
Nesher G, Zion MM. Recu­rrent ven­tri­cu­lar tachy­car­dia in hypothy­roi­dism – report of a case and review
of the lite­ra­ture. Car­dio­logy. 1988;75(4):301 – 6
Shaare Zedek Medi­cal Cen­ter, Jeru­sa­lem, Israel
Fred­lund BO, Ols­son SB. Long QT inter­val and ven­tri­cu­lar tachy­car­dia of “tor­sade de pointe” type in
hypothy­roi­dism. Acta Med Scand. 1983;213(3):231 – 5

Low serum T3 and T4 in patients with coro­nary heart disease

Miura S, Iitaka M, Suzuki S, Fuka­sawa N, Kitahama S, Kawa­kami Y, Saka­tsume Y, Yama­naka K, Kawa­saki S, Kinoshita S, Kata­yama S, Shi­bo­sawa T, Ishii J. Dec­rease in serum levels of thy­roid hor­mone in patients with coro­nary heart disease. Endocr J. 1996 Dec;43(6):657 – 63

Low serum free T3 in patients with coro­nary bypass: inc­rea­sed risk of pos­to­pe­ra­tive atrial fibri­lla­tion (higher risk than that of not taking a beta-blocker)

Ceri­llo AG, Bevi­lac­qua S, Storti S, Mariani M, Kallushi E, Ripoli A, Cle­rico A, Glau­ber M. Free triio­dothy­ro­nine: a novel pre­dic­tor of pos­to­pe­ra­tive atrial fibri­lla­tion. Eur J Car­diotho­rac Surg. 2003 Oct;24(4):487 – 92

Pro­gres­si­vely lower serum T3 in patients with ische­mic heart disease: form coro­nary ste­no­sis to myco­car­dial infarct

Tel­kova IL, Teplia­kov AT. Chan­ges of thy­roid hor­mone levels in the pro­gres­sion of coro­nary artery disease. Arte­riosc­le­ro­sis. Klin Med (Mosk). 2004;82(4):29 – 34
Pav­lou HN, Kli­ri­dis PA, Pana­gio­to­pou­los AA, Gori­tsas CP, Vas­si­la­kos PJ. Euthy­roid sick syn­drome in acute ische­mic syn­dro­mes. Angio­logy. 2002 Nov-Dec;53(6):699 – 707
Pime­nov LT, Leshchins­kii LA. Thy­roid hor­mone chan­ges (iodothy­ro­ni­ne­mia) in patients with acute myo­car­dial infarc­tion, and their cli­ni­cal sig­ni­fi­cance. Kar­dio­lo­giia. 1984 Oct;24(10):74 – 7

Low serum free and total T3 (and low free T4 and high TSH) in patients suf­fe­ring from acute myco­car­dial infarct with poor outcome

Satar S, Sey­dao­glu G, Avci A, Sebe A, Kar­cio­glu O, Topal M. Prog­nos­tic value of thy­roid hor­mone levels in acute myo­car­dial infarc­tion: just an epiphe­no­me­non? Am Heart Hosp J. 2005 Fall;3(4):227 – 33

Auto-immune throi­diits is asso­cia­ted with poo­rer heart indices

Zoncu S, Pigliaru F, Putzu C, Pisano L, Var­giu S, Deidda M, Mariotti S, Mer­curo G. Car­diac func­tion in bor­der­line hypothy­roi­dism: a study by pul­sed wave tis­sue Dop­pler ima­ging. Eur J Endoc­ri­nol. 2005 Apr;152(4):527 – 33 (impair­ment of sys­to­lic ejec­tion, a delay in dias­to­lic rela­xa­tio­nand a dec­rease in the com­pliance to the ven­tri­cu­lar filling. Seve­ral sig­ni­fi­cant corre­la­tions were found bet­ween the para­me­ters and serum-free T(3) and T(4) and TSH con­cen­tra­tions. Data strongly sup­port the con­cept of a con­ti­nuum spec­trum of a slight thy­roid fai­lure in autoim­mune thy­roi­di­tis)
Depart­ment of Car­dio­vas­cu­lar Scien­ces, Uni­ver­sity of Cagliari, Sar­di­nia, Italy

Inc­rea­sed inci­dence of auto-immune thy­roi­di­tis and overt hypothy­roi­dism in men with acute myco­car­dial infarct, which may have con­tri­bu­ted to the deve­lop­ment of the disease.

Ceri­llo AG, Bevi­lac­qua S, Storti S, Mariani M, Kallushi E, Ripoli A, Cle­rico A, Glau­ber M. Free triio­dothy­ro­nine: a novel pre­dic­tor of pos­to­pe­ra­tive atrial fibri­lla­tion. Eur J Car­diotho­rac Surg. 2003 Oct;24(4):487 – 92

A low serum T3 or T4 (hypothy­roi­dism) is found in car­diac failure:

Kha­leeli AA, Memon N. Fac­tors affec­ting reso­lu­tion of peri­car­dial effu­sions in pri­mary hypothy­roi­dism: a cli­ni­cal, bioche­mi­cal and echo­car­dio­graphic study. Post­grad Med J. 1982 Aug;58(682):473 – 6
Reza MJ, Abbasi AS. Con­ges­tive car­diom­yo­pathy in hypothy­roi­dism. West J Med. 1975 Sep;123(3):228 – 30
Rays J, Wajn­gar­ten M, Gebara OC, Nuss­bacher A, Telles RM, Pie­rri H, Rosano G, Serro-Azul JB. Long-term prog­nos­tic value of triio­dothy­ro­nine con­cen­tra­tion in elderly patients with heart fai­lure. Am J Geriatr Car­diol. 2003 Sep-Oct;12(5):293 – 7 (Lower serum T3 in car­diac fai­lure: The odds ratio for events was 9.8 (95% con­fi­dence interval,2.2 – 43, p=0.004) for patients in the lowest ter­tile of triio­dothy­ro­nine, that is, lower than 80 ng/dL, com­pa­red with patients with levels above 80 ng/dL)
Divi­sion of Geria­tric Car­dio­logy, Heart Ins­ti­tute (InCor), Uni­ver­sity of Sao Paulo Medi­cal School, Sao Paolo, Bra­zil
Pin­gi­tore A, Landi P, Tad­dei MC, Ripoli A, L’Abbate A, Ier­vasi G. Triio­dothy­ro­nine levels for risk stra­ti­fi­ca­tion of patients with chro­nic heart fai­lure. Am J Med. 2005 Feb;118(2):132 – 6
Ins­ti­tute of Cli­ni­cal Phy­sio­logy, C.N.R., Pisa, Italy. pingi@ifc.cnr.it
Klein I, Ojama K. In: Wer­ner & Ingbar’s The Thy­roid, ed. Bra­ver­man LE & Uti­ger RD, Lippincott-Raven Publishers, Phi­la­delphia, 1996, 62: 799 – 804

A low serum free T3 index/reverse T3 ratio in chro­nic heart fai­lure patients is a highly sig­ni­fi­cant pre­dic­tor of poor outcome

Ceri­llo AG, Bevi­lac­qua S, Storti S, Mariani M, Kallushi E, Ripoli A, Cle­rico A, Glau­ber M. Free triio­dothy­ro­nine: a novel pre­dic­tor of pos­to­pe­ra­tive atrial fibri­lla­tion. Eur J Car­diotho­rac Surg. 2003
Hamil­ton MA, Ste­ven­son LW, Luu M, Wal­den JA. Alte­red thy­roid hor­mone meta­bo­lism in advan­ced heart fai­lure. J Am Coll Car­diol. 1990 Jul;16(1):91 – 5
Divi­sion of Car­dio­logy, Uni­ver­sity of Cali­for­nia, Los Ange­les School of Medi­cine 90024 – 1679
Koz­dag G, Ural D, Vural A, Agac­di­ken A, Kah­ra­man G, Sahin T, Ural E, Kom­suo­glu B. Rela­tion bet­ween free triiodothyronine/free thy­ro­xine ratio, echo­car­dio­graphic para­me­ters and mor­ta­lity in dila­ted car­diom­yo­pathy. Eur J Heart Fail. 2005 Jan;7(1):113 – 8
Depart­ment of Car­dio­logy, Kocaeli Uni­ver­sity, Yah­ya­kap­tan Mah. A4 Blok Daire:3, Kocaeli 41050, Tur­key. gkozdag@superonline.com

A low serum T3 or T4 in heart patients is asso­cia­ted with an inc­rea­sed risk of car­diac arrest/death

Worts­man J, Pre­machan­dra BN, Cho­pra IJ, Murphy JE. Hypothy­ro­xi­ne­mia in car­diac arrest. Arch Intern Med. 1987 Feb;147(2):245 – 8
Ier­vasi G, Pin­gi­tore A, Landi P, Raciti M, Ripoli A, Scar­lat­tini M, L’Abbate A, Donato L. Low-T3 syn­drome: a strong prog­nos­tic pre­dic­tor of death in patients with heart disease. Cir­cu­la­tion. 2003 Feb 11;107(5):708 – 13

Car­dio­vas­cu­lar disease and mor­ta­lity isinc­rea­sed in hypothy­roi­dism (+ 70 % for both)

Dorr M, Volzke H. Car­dio­vas­cu­lar mor­bi­dity and mor­ta­lity in thy­roid dys­func­tion. Minerva Endoc­ri­nol. 2005 Dec;30(4):199 – 216
Depart­ment of Inter­nal Medi­cine B, Ernst-Moritz-Arndt-University, Greifs­wald, Germany

Thy­roid the­rapy ot car­diac patients

Correc­tive thy­roid the­rapy is safe in patients with com­mon benign car­diac arrhyth­mias (under the con­di­tion that thy­roid treat­ment is star­ted at low doses and then gra­dually and pru­dently inc­rea­sed to the ade­quate dose). The treat­ment does not trig­ger an inc­rease in arrhyth­mia fre­quency except in rare patients with base­line atrial pre­ma­ture beats. It is, howe­ver, asso­cia­ted with an inc­rease in basal, ave­rage and maxi­mal heart rates

Poli­kar R, Feld GK, Dit­trich HC, Smith J, Nicod P. Effect of thy­roid repla­ce­ment the­rapy on the fre­quency of benign atrial and ven­tri­cu­lar arrhyth­mias. J Am Coll Car­diol. 1989 Oct;14(4):999‑1002
Divi­sion of Car­dio­logy, Uni­ver­sity of Cali­for­nia, San Diego. 

Thy­roid the­rapy corrects the brady­car­dia of hypothyroidism

Yamauchi K, Takasu N, Ichi­kawa K, Yamada T, Aizawa T. Effects of long-term treat­ment with thy­ro­xine on pitui­tary TSH sec­re­tion and heart action in patients with hypothy­roi­dism. Acta Endoc­ri­nol (Copenh). 1984 Oct;107(2):218 – 24 (T4 doses should be adjus­ted to main­tain nor­mal ET/PEP (sys­to­lic time inter­vals) rather than nor­mal serum TSH levels

Thy­roid the­rapy corrects the ven­tri­cu­lar arrhythmia

Vanin LN, Smet­nev AS, Soko­lov SF, Kotova GA, Masenko VP. Thy­roid func­tion in patients with ven­tri­cu­lar arrhyth­mia. Kar­dio­lo­giia. 1989 Feb;29(2):64 – 7 (Thy­roid the­rapy for hypothy­roi­dism led to the disap­pea­rance of paroxysms of ven­tri­cu­lar tachy­car­dia and redu­ced the total num­ber and gra­des of ven­tri­cu­lar extra-systoles in patients with ven­tri­cu­lar arrhyth­mias; moreo­ver, sen­si­ti­vity to antiarrhyth­mic agents deve­lo­ped to replace an ear­lier resistance)

Coro­nary heart disease in humans: the impro­ve­ment with thy­roid treatment

Bar­nes BO. Prophy­la­xis of ischae­mic heart-disease by thy­roid the­rapy. Lan­cet. 1959 Aug 22;2:149 – 52
Holland FW 2^nd, Brown PS Jr, Clark RE. Acute severe pos­tische­mic myo­car­dial depres­sion rever­sed by triio­dothy­ro­nine. Ann Tho­rac Surg. 1992 Aug;54(2):301 – 5
Israel M. An effec­tive the­ra­peu­tic approach to the con­trol of athe­rosc­le­ro­sis illus­tra­ting harm­less­ness of pro­lon­ged use of thy­roid hor­mone in coro­nary disease. Am J Dig Dis. 1955 June;161 – 8
Yokohama et al, Car­dio­logy, 1992, 81 (1): 34 – 45;

Ade­quate thy­ro­xine repla­ce­ment in hypothy­roi­dism pre­vents coro­nary artery disease progression 

Perk M, O’Neill BJ; The effect of thy­roid the­rapy on angio­graphic artery disease pro­gres­sion . Can J Card. 1997;13(3):273 – 6

(Des­si­ca­ted) thy­roid the­rapy impro­ves car­diac fai­lure refrac­tory to digi­ta­lis in humans

Zon­dek H. Myxe­dema Heart. Munch Med Wochenschr. 1918, 65: 1180 – 3
Kha­leeli AA, Memon N. Fac­tors affec­ting reso­lu­tion of peri­car­dial effu­sions in pri­mary hypothy­roi­dism: a cli­ni­cal, bioche­mi­cal and echo­car­dio­graphic study. Post­grad Med J. 1982 Aug;58(682):473 – 6

T3-therapyimproves the out­come of open heart sugery, espe­cially heart transplants

Novitzky D, Fon­ta­net H, Sny­der M, Coblio N, Smith D, Par­son­net V. Impact of triio­dothy­ro­nine on the sur­vi­val of high-risk patients under­going open heart sur­gery. Car­dio­logy. 1996 Nov-Dec;87(6):509 – 15.
Novitzky D, Coo­per DK, Chaf­fin JS, Greer AE, DeBault LE, Zuhdi N. Impro­ved car­diac allo­graft func­tion follo­wing triio­dothy­ro­nine the­rapy to both donor and reci­pient. Trans­plan­ta­tion. 1990 Feb;49(2):311 – 6

Thy­roid hor­mone the­rapy greatly redu­ces the lesions of expe­ri­men­tal myo­car­dial infarct in rats 

Holland FW, Brown PS, Clark RE. Acute severe pos­tische­mic myo­car­dial depres­sion rever­sed by triio­dothy­ro­nine. Ann Tho­rac Surg 1992 54: 301 – 305

Thy­roid the­rapy redu­ces coro­nary artery disease and car­diac fibro­sis in mice

Yao J, Egh­bali M. Dec­rea­sed colla­gen mRNA and regres­sion of car­diac fibro­sis in the ven­tri­cu­lar myo­car­dium of the tight skin mouse follo­wing thy­roid hor­mone treat­ment. Car­dio­vasc Res. 1992 Jun;26(6):603 – 7

Thy­roid the­rapy redu­ced the lesions of expe­ri­men­tal car­diac arrest in dogs

Fack­tor MA, Mayor GH, Nach­rei­ner RF, D’Alecy LG. Thy­roid hor­mone loss and repla­ce­ment during resus­ci­ta­tion from car­diac arrest in dogs. Resus­ci­ta­tion. 1993 Oct;26(2):141 – 62

Thy­roid the­rapy redu­ced the com­pli­ca­tions of hemorrha­gic shock in dogs

Shi­ge­ma­tsu H, Shat­ney CH. The effect of triio­dothy­ro­nine (T3) and reverse triio­dothy­ro­nine (rT3) on canine hemorrha­gic shock. Nip­pon Geka Gak­kai Zasshi. 1988 Oct;89(10):1587 – 93.

Thy­roid The­rapy and Bone Density

Stu­dies with asso­cia­tion bet­ween thy­roid the­rapy and inc­rea­sed loss of bone den­sity

Bone loss during thy­roid treat­ment mainly occurs in HRT untrea­ted post­me­no­pau­sal women and who have a sup­pres­sed TSH, pos­sibly being over­trea­ted with thy­roid hormones 

Tael­man P, Kauf­man JM, Jans­sens X, Van­de­cau­ter H, Ver­meu­len A. Redu­ced forearm bone mine­ral con­tent and bioche­mi­cal evi­dence of inc­rea­sed bone tur­no­ver in women with euthy­roid goi­tre trea­ted with thy­roid hor­mone. Clin Endoc­ri­nol (Oxf). 1990 Jul;33(1):107 – 17
Stall GM, Harris S, Sokoll LJ, Dawson-Hughes B. Acce­le­ra­ted bone loss in hypothy­roid patients over­trea­ted with L-thyroxine. Ann Intern Med. 1990 Aug 15;113(4):265 – 9
Adlin EV, Mau­rer AH, Marks AD, Chan­nick BJ. Bone mine­ral den­sity in post­me­no­pau­sal women trea­ted with L-thyroxine. Am J Med. 1991 Mar;90(3):360 – 6
Paul TL, Kerri­gan J, Kelly AM, Bra­ver­man LE, Baran DT. Long-term L-thyroxine the­rapy is asso­cia­ted with dec­rea­sed hip bone den­sity in pre­me­no­pau­sal women. JAMA. 1988;259:3137 – 41

Bone loss is mainly tran­si­tory only during the first year with no inc­rea­sed frac­ture incidence

Tre­mo­llie­res F, Poui­lles JM, Lou­vet JP, Ribot C. Tran­si­tory bone loss during subs­ti­tu­tion treat­ment for hypothy­roi­dism. Results of a two year pros­pec­tive study. Rev Rhum Mal Osteoar­tic. 1991 Dec;58(12):869 – 75
Ribot C, Tre­mo­llie­res F, Poui­lles JM, Lou­vet JP. Bone mine­ral den­sity and thy­roid hor­mone the­rapy. Clin Endoc­ri­nol (Oxf). 1990 Aug;33(2):143 – 53

Oes­tro­gen the­rapy neu­tra­li­zes, pre­vents bone loss indu­ced by correc­tive thy­roid therapy

45. Sch­nei­der DL, Barrett-Connor EL, Mor­ton DJ. Thy­roid hor­mone use and bone mine­ral den­sity in elderly women. JAMA 1994;271:1245 – 9 

Stu­dies where thy­roid the­rapy does not cause or inc­rease loss of bone density 

43. Greens­pan SL, Greens­pan FS, Res­nick NM, Block JE, Fried­lan­der AL, Genant HK. Ske­le­tal inte­grity in pre­me­no­pau­sal and post­me­no­pau­sal women recei­ving long-term L-thyroxine the­rapy Am J Med. 1991;91:5 – 14
44. Franklyn JA, Bet­te­ridge J, Day­kin J, Hol­der R, Oates GD, Parle JV, Lilley J, Heath DA, Shep­pard MC. Long-term thy­ro­xine treat­ment and bone mine­ral den­sity. Lan­cet. 1992 Jul 4;340(8810):9 – 13
Depart­ment of Medi­cine, Uni­ver­sity of Bir­mingham, UK
Eulry F, Bau­du­ceau B, Leche­va­lier D, Mag­nin J, Cro­zes P, Fla­geat J, Gau­tier D. Bone den­sity in dif­fe­ren­tia­ted can­cer of the thy­roid gland trea­ted by hormone-suppressive the­rapy. Study based on 51 cases. Rev Rhum Mal Osteoar­tic. 1992 Apr;59(4):247 – 52
Grant DJ, McMurdo ME, Mole PA, Pater­son CR, Davies RR. Sup­pres­sed TSH levels secon­dary to thy­ro­xine repla­ce­ment the­rapy are not asso­cia­ted with osteo­po­ro­sis. Clin Endoc­ri­nol (Oxf). 1993 Nov;39(5):529 – 33.

Stu­dies where thy­roid the­rapy impro­ves bone formation

Svan­berg E, Hea­ley J, Mas­ca­renhas D. Ana­bo­lic effects of rhIGF-I/IGFBP-3 in vivo are influen­ced by thy­roid sta­tus. Eur J Clin Invest. 2001 Apr;31(4):329 – 36