TEIL 3 der SD-relevanten Referenzen aus Dr. Thierry Hertoghe's Buch ?The Hormone Handbook? (ed. International medical books, www.imbooks.info/)
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
1. 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)
2. 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.?)
3. 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.?)
4. 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 children 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?).
5. 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
6. Johnston MW, Squires AH, Farquharson RF. The effect of prolonged administration of thyroid. Ann Intern Med. 1951 Nov;35(5):1008-22
7. Riggs DS, Man EB, Winkler AW. Serum iodine of euthyroid subjects treated with dessicated thyroid. J Clin Invest. 1945;24:722-31
8. 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
9. 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
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!)
1. 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
2. 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
3. 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
4. Kabadi UM. ?Subclinical hypothyroidism:? natural course of the syndrome during a prolonged follow-up study. Arch Intern Med. 1993;153:957-61
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)
5. 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
6. 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
7. Cooper DS 2001 Subclinical hypothyroidism. N Engl J Med 345:260?5
8. Ayala A, Wartofsky L. Minimally symptomatic (subclinical) hypothyroidism. Endocrinologist. 1997;7:44?50
9. 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
10. 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
11. 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
12. Faber J, Petersen L, Wiinberg N, Schifter S, Mehisen J. Hemodynamic changes after levothyroxine treatment in subclinical hypothyroidism. Thyroid. 2002; 12:319?24
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
24. Joffe RT, Levitt AJ 1992 Major depression and subclinical (grade 2) hypothyroidism. Psychoneuroendocrinology. 17:215?21
25. 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
26. 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
27. 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
28. 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
29. 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
30. 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
31. Misiunas A, Ravera HN, Faraj G, Faure E. Peripheral neuropathy in subclinical hypothyroidism. Thyroid 1995;5:283?6
32. 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
33. 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
34. 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
35. Foundation for Blood Research, Scarborough, ME 04074, USA
36. 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
37. Cooper DS, Halpern R, Wood LC, Levin AA, Ridgway EC. L-thyroxine therapy in subclinical hypothyroidism. Ann Intern Med. 1984;101:18?24
38. 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)
39. 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
40Forfar 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
41. Kahaly GJ 2000 Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid 10:665?79
42. 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
43. 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
44. 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.
45. 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
46. 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
47. 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
48. 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
49. 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
50. 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
51. 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
52. 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.
53. 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
54. 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
55. Perk M, O?Neill BJ. The effect of thyroid hormone therapy on angiographic coronary artery disease progression. Can J Cardiol. 1997;13:273?6
56. 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
57. Danese MD, Powe NR, Sawin CT, Ladenson PW. Screening for mild thyroid failure at the periodic health examination. JAMA. 1996;276:285?92
58. 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
59. 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
60. 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.
Important frequency of subclinical hypothyroidism:
61. Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG,
62. 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
63. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:526?34
64. 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. 72nd Annual Meeting of the American Thyroid Association, Palm Beach, FL, 1999; Abstract 213
65. 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
66. 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
67. 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
68. 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
69. 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
70. 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
71. Rosenthal MJ, Hunt WC, Garry PJ, Goodwin JS. Thyroid failure in the elderly: microsomal antibodies as discriminant for therapy. JAMA. 1987 ;258:209?13
72. 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)
Important risk of progression into overt hypothyrodism:
73. 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
74. Bastenie PA, Bonnyns M, Vanhaelst L. Natural history of primary myxedema. Am J Med. 1985;79:91?100
75. Kabadi UM. Subclinical hypothyroidism. Natural course of the syndrome during a prolonged follow-up study. Arch Intern Med. 1993;153:957?61
76. 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
77. 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
78. Wang C, Crapo LM. The epidemiology of thyroid disease and implications for screening. Endocrinol Metab Clin North Am. 1997;26:189?218
79. 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. 71st Annual Meeting of the American Thyroid Association, Portland, OR, 1998; Abstract 109
Importance of clinical evaluation of subclinical hypothyroidism
80. 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
81. 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
82. 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
83. Dluhy RG, Williams GH. Aldosterone: villain or bystander? N Engl J Med. 2004;351:8?10
Arguments CONTRA THYROID USE for mild thyroid failure
84. Chu JW, Crapo LM. Should mild hypothyroidism be treated? Am J Med. 2002;112:422?3
85. 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)
86. 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
87. 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
88. 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) a TSH 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)
89. 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
90. 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
91. 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
92. 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
93. 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
1. Brent GA, Larsen PR. Treatment of hypothyroidism. In: Braverman LE, Utiger RD, ed. Werner and Ingbar?s. The Thyroid: A Fundamental and Clinical Text. 7th ed., 1996, Philadelphia, Ravens- Lippincott Publishers
2. Utiger RD. Hypothyroidism. In DeGroot LJ et al, eds. Endocrinology, Vol 1. 2nd ed. Philadelphia, Pa: WB Saunders Co, 1989;702-21
3. Mandel SJ, Brent GA, Larsen PR. Levothyroxine therapy in patients with thyroid disease. Ann Intern Med 1993;119:492-502
4. Roti E, Braverman LE. Thyroid hormone therapy: when to use it, when to avoid it. Drug Therapy. 1994; 24(4):2-35.
Arguments pro treatment with either T4 alone, either T4 and T3
T4 and T3- work as good as T4 alone, but not better
5. 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
6. 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
Arguments pro treatment with T4 and T3 combinations
T3-T4 (and T3) work better than T4
7. 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
8. 1032. Kloppenburg M, Dijkmans BA, Rasker JJ. Effect of therapy for thyroid dysfunction on musculoskeletal symptoms. Clin Rheumatol. 1993 Sep;12(3):341-5
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. Gross J, Pitt-Rivers R. Physiological activity of 3:5:3?-L-triiodothyronine. Lancet. 1952 Mar 22;1(12):593-4
21. 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.
22. Burroughs V, Shenkman L. Thyroid function in the elderly. Am J Med Sci. 1982, 283 (1): 8-17
23. 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
24. 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
25. Katzeff HI, Selgrad C. Impaired peripheral thyroid hormone metabolism in genetic obesity. Endocrinology. 1993; 132 (3): 989-95
26. Croxson MS and Ibbertson HK. Low serum triiodothyronine (T3) and hypothyroidism in anorexia nervosa. J Clin Endocrinol Metab. 1977; 44: 167-73
27. 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
28. 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
29. 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
30. Feyes D, Hennemann G and Visser TJ. Inhibition of iodothyronine deiodinase by phenolphtalein dyes. Fed Eur Biomed Sci. 1982; 137(1):40-4
31. 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
32. 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
33. 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
34. 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
35. 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
36. 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
37. 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
38. 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
39. 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
40. Gavin LA, Mahon FA, Moeller M. The mechanism of impaired T3 production from T4 in diabetes. Diabetes. 1981;30:694-9
41. 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
42. 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
43. Arthur JR, Nicol F, Beckett GJ. Selenium deficiency, thyroid hormone metabolism, and thyroid hormone deiodinases. Am J Clin Nutr Suppl. 1993; 57:236S-9S
44. Beard J, Tobin B, and Green W. Evidence for thyroid hormone deficiency in iron-deficient anemic rats. J Nutr. 1989;772-8
45. 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
46. 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
47. 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 (glucocorticoids, ACTH, estrogens,?) and trace elements (iodine, lithium, ?) may slow down this conversion.
48. 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
49. 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
50. 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
51. 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 %), contrasting with that of T3 that is more constant and efficient (95%)
52. Hays MT. Absorption of oral thyroxine in man. J Clin Endocrinol Metab. 1968; 28 (6):749-56
53. 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
54. Hays MT. Absorption of triidothyronine in man. J Clin Endocrinol Metab. 1970; 30(5):675-6
Defects in the commercial T4 preparation
55. Hubbard WK. FDA notice regarding levothyroxine sodium. Federal register. 1997; 62(157): 1-10
56. 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 treatment 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)
1. 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
2. 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
3. Parmar MS. Thyrotoxic atrial fibrillation. Med Gen Med. 2005 Jan 4;7(1):74 (atrial fibrillation was seen in 15 % of hyperthyroid patients)
4. 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
5. 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.
Hyperthyroidism is associated with an increased risk of angina pectoris
6. 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
7. 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??)
8. 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)
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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%)
15. 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
16. 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
17. 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
18. 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)
19. 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
20. 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
21. 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
22. 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
23. 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
24. 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.
25. 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:
26. 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
27. Reza MJ, Abbasi AS. Congestive cardiomyopathy in hypothyroidism. West J Med. 1975 Sep;123(3):228-30
28. 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
29. 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.
30. 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
31. 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
32. 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
33. 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.
A low serum T3 or T4 in heart patients is associated with an increased risk of cardiac arrest/death
34. Wortsman J, Premachandra BN, Chopra IJ, Murphy JE. Hypothyroxinemia in cardiac arrest. Arch Intern Med. 1987 Feb;147(2):245-8
35. 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)'
36. 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
37. 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
38. 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
39. 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
40. Barnes BO. Prophylaxis of ischaemic heart-disease by thyroid therapy. Lancet. 1959 Aug 22;2:149-52
41. Holland FW 2nd, Brown PS Jr, Clark RE. Acute severe postischemic myocardial depression reversed by triiodothyronine. Ann Thorac Surg. 1992 Aug;54(2):301-5
42. 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
43. Yokohama et al, Cardiology, 1992, 81 (1): 34-45;
Adequate thyroxine replacement in hypothyroidism prevents coronary artery disease progression
44. 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
45. Zondek H. Myxedema Heart. Munch Med Wochenschr. 1918, 65: 1180-3
46. 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
47. 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.
48. 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
49. 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
50. 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
51. 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
52. 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
1. 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
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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
11. 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