Subclinical hypothyroidism is a common finding when serum thyrotropin and thyroid hormones are measured, but the benefits of treating such patients with levothyroxine remain unproven. During the 14th International Thyroid Congress, a debate and discussion relating to three different clinical case scenarios of subclinical hypothyroidism was held. The audience consisted predominantly of members of the European Thyroid Association. Participants (n = 380) voted using an electronic system to express their opinion about the treatment of the 3 cases. For a 53-year-old woman with fatigue and difficulty losing weight, who has a serum TSH of 6.8 mU/l, 49% would treat with levothyroxine. Whereas, for an 84-year-old woman with a serum TSH of 6.8 mU/l, only 8% of participants would treat with levothyroxine. In contrast, for a 39-year-old woman who is trying to become pregnant, with a serum TSH of 4.5 mU/l and strongly positive thyroid peroxidase antibodies, 95% of respondents would treat with levothyroxine. This article details the clinical case scenarios and the results of the thyroidologists’ opinions on treatment. It forms a snapshot of the range of accepted clinical practice in this common condition.

1.
Evered DC, Ormston BJ, Smith PA, Hall R, Bird T: Grades of Hypothyroidism. Br Med J 1973;5854:657–662.
2.
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 1977;7:481–493.
3.
Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE: Serum TSH, T4, and thyroid antibodies in the United States population (1988–1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489–499.
4.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC: The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526–534.
5.
Razvi S, Ingoe LE, McMillan CV, Weaver JU: Health status in patients with sub-clinical hypothyroidism. Eur J Endocrinol 2005;152:713–717.
6.
Reuters VS, Teixeira PF, Vigário PS, Almeida CP, Buescu A, Ferreira MM, de Castro CL, Gold J, Vaisman M: Functional capacity and muscular abnormalities in subclinical hypothyroidism. Am J Med Sci 2009;338:259–263.
7.
Mainenti MR, Vigário PS, Teixeira PF, Maia MD, Oliveira FP, Vaisman M: Effect of levothyroxine replacement on exercise performance in subclinical hypothyroidism. J Endocrinol Invest 2009;32:470–473.
8.
Cooper DS, Halpern R, Wood LC, Levin AA, Ridgway EC: L-Thyroxine therapy in subclinical hypothyroidism. A double-blind, placebo-controlled trial. Ann Intern Med 1984;101:18–24.
9.
Jorde R, Waterloo K, Storhaug H, Nyrnes A, Sundsfjord J, Jenssen TG: Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment. J Clin Endocrinol Metab 2006;91:145–153.
10.
Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU: The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab 2007;92:1715–1723.
11.
Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC: Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 2000;132:270–278.
12.
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;89:3365–3370.
13.
Walsh JP, Bremner AP, Bulsara MK, O’Leary P, Leedman PJ, Feddema P, Michelangeli V: Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med 2005;165:2467–2472.
14.
Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, Bauer DC: Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med 2005;165:2460–2466.
15.
Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, Rodondi N: Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med 2008;148:832–845.
16.
Razvi S, Shakoor A, Weaver JU, Vanderpump M, Pearce SH: The influence of age on ischaemic heart disease and mortality in subclinical hypothyroidism – a meta-analysis. J Clin Endocrinol Metab 2008;93:2998–3007.
17.
Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH, Bremner A, Maisonneuve P, Sgarbi JA, Khaw KT, Vanderpump MP, Newman AB, Cornuz J, Franklyn JA, Westendorp RG, Vittinghoff E, Gussekloo J, Thyroid Studies Collaboration: Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010;304:1365–1374.
18.
Danese MD, Ladenson PW, Meinert CL, Powe NR: Clinical review 115: 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.
19.
Teixeira PF, Reuters VS, Ferreira MM, Almeida CP, Reis FA, Melo BA, Buescu A, Costa AJ, Vaisman M: Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a placebo-controlled double-blind clinical trial. Horm Metab Res 2008;40:50–55.
20.
Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C, Ferranini E: Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab 2001;86:1110–1115.
21.
Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, Salvetti D, Ferranini E, Monzani F: Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab 2003;88:3731–3737.
22.
Cabral MD, Teixeira PF, Silva NA, Morais FF, Soares DV, Salles E, Henriques JM, Leite SP, Montenegro CA, Vaisman M: Normal flow-mediated vasodilatation of the brachial artery and carotid artery intima-media thickness in subclinical hypothyroidism. Braz J Med Biol Res 2009;42:426–432.
23.
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;291:228–238.
24.
UK Guidelines for the Use of Thyroid Function Tests: Association of Clinical Biochemistry, British Thyroid Association, British Thyroid Foundation. www.british-thyroid-association.org/TFT_guideline_final_version_July_2006.pdf
25.
Haute Autorité de santé Hypothyroïdies frustes chez l’adulte: diagnostic et prise en charge, Avril 2007. www.has-sante.fr/portail/jcms/c_598104/hypothyroidies-frustes-chez-l-adulte-diagnostic-et-prise-en-charge
26.
Parle JV, Franklyn JA, Cross KW, Jones SR, Sheppard MC: Thyroxine prescription in the community: serum thyroid-stimulating hormone level assays as an indicator of undertreatment or overtreatment. Br J Gen Pract 1993;43:107–109.
27.
Faber J, Galløe AM: Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis. Eur J Endocrinol 1994;130:350–356.
28.
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;331:1249–1252.
29.
Vaidya B, Pearce SHS: Management of hypothyroidism in adults. BMJ 2008;337:284–289.
30.
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;11:757–764.
31.
Mariotti S, Franceschi C, Cossarizza A, Pinchera A: The aging thyroid. Endocr Rev 1995;16:686–715.
32.
Surks MI, Hollowell JG: Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab 2007;92:4575–4582.
33.
Parle JV, Maisonneuve P, Sheppard 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;358:861–865.
34.
Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG: Thyroid status, disability and cognitive function, and survival in old age. JAMA 2004;292:2591–2599.
35.
Cooper DS: Clinical practice. Subclinical hypothyroidism. N Engl J Med 2001;345:260–265.
36.
Glinoer D, Riahi M, Grün JP, Kinthaert J: Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab 1994;79:197–204.
37.
Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A: Increased pregnancy loss rate in thyroid antibody-negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab 2010;95:E44–E48.
38.
Stagnaro-Green A: Maternal thyroid disease and preterm delivery. J Clin Endocrinol Metab 2009;94:21–25.
39.
Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H: Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 2006;91:2587–2591.
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