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Subclinical hyperthyroidism

Douglas S Ross, MD
Section Editor
David S Cooper, MD
Deputy Editor
Jean E Mulder, MD


The availability of sensitive assays for thyroid-stimulating hormone (TSH) resulted in the identification of patients who have low serum TSH concentrations (<0.5 mU/L) but normal serum free thyroxine (T4) and triiodothyronine (T3) concentrations, a constellation of biochemical findings defined as subclinical hyperthyroidism. The term overt hyperthyroidism refers to patients with elevated levels of free T4, T3, or both, and a subnormal TSH concentration. Both subclinical and overt hyperthyroidism are biochemical definitions, since hyperthyroid symptoms are non-specific and may be present in patients with subclinical disease and absent in those with overt disease, especially older adults.

Subclinical hyperthyroidism will be discussed here. Overt hyperthyroidism is discussed separately. (See "Diagnosis of hyperthyroidism" and "Overview of the clinical manifestations of hyperthyroidism in adults".)


The causes of subclinical hyperthyroidism are the same as the causes of overt hyperthyroidism and, like overt hyperthyroidism, subclinical hyperthyroidism can be persistent or transient (table 1). (See "Disorders that cause hyperthyroidism".)

Exogenous subclinical hyperthyroidism — As many as 10 million people in the United States, and possibly as many as 200 million people worldwide, are taking thyroid hormone. All are at risk for subclinical hyperthyroidism, whether intentional or unintentional. Among patients taking thyroxine (T4), as many as 25 percent have low serum thyroid-stimulating hormone (TSH) values [1,2], and in one study, 5.8 percent were under 0.1 mU/L [3]. (See "Exogenous hyperthyroidism".)

Many of these patients have hypothyroidism, and in them subclinical hyperthyroidism is not the goal of thyroid hormone therapy. However, subclinical hyperthyroidism is the goal of thyroid hormone therapy in patients with thyroid cancer and in some patients with solitary thyroid nodules, multinodular or diffuse goiters, or a history of head and neck irradiation. In these patients, the benefits of TSH suppression are thought to outweigh the risks of subclinical hyperthyroidism. (See "Differentiated thyroid cancer: Overview of management", section on 'Thyroid hormone suppression' and "Thyroid hormone suppressive therapy for thyroid nodules and benign goiter".)


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Literature review current through: Jul 2016. | This topic last updated: Dec 30, 2014.
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  1. De Whalley P. Do abnormal thyroid stimulating hormone level values result in treatment changes? A study of patients on thyroxine in one general practice. Br J Gen Pract 1995; 45:93.
  2. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160:526.
  3. Taylor PN, Iqbal A, Minassian C, et al. Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study. JAMA Intern Med 2014; 174:32.
  4. Díez JJ. Hyperthyroidism in patients older than 55 years: an analysis of the etiology and management. Gerontology 2003; 49:316.
  5. Rieu M, Bekka S, Sambor B, et al. Prevalence of subclinical hyperthyroidism and relationship between thyroid hormonal status and thyroid ultrasonographic parameters in patients with non-toxic nodular goitre. Clin Endocrinol (Oxf) 1993; 39:67.
  6. Charkes ND. The many causes of subclinical hyperthyroidism. Thyroid 1996; 6:391.
  7. Kasagi K, Hatabu H, Tokuda Y, et al. Studies on thyrotrophin receptor antibodies in patients with euthyroid Graves' disease. Clin Endocrinol (Oxf) 1988; 29:357.
  8. Murakami M, Koizumi Y, Aizawa T, et al. Studies of thyroid function and immune parameters in patients with hyperthyroid Graves' disease in remission. J Clin Endocrinol Metab 1988; 66:103.
  9. Sawin CT, Geller A, Kaplan MM, et al. Low serum thyrotropin (thyroid-stimulating hormone) in older persons without hyperthyroidism. Arch Intern Med 1991; 151:165.
  10. Eggertsen R, Petersen K, Lundberg PA, et al. Screening for thyroid disease in a primary care unit with a thyroid stimulating hormone assay with a low detection limit. BMJ 1988; 297:1586.
  11. Bagchi N, Brown TR, Parish RF. Thyroid dysfunction in adults over age 55 years. A study in an urban US community. Arch Intern Med 1990; 150:785.
  12. Parle JV, Franklyn JA, Cross KW, et al. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf) 1991; 34:77.
  13. 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; 78:1368.
  14. Sundbeck G, Jagenburg R, Johansson PM, et al. Clinical significance of low serum thyrotropin concentration by chemiluminometric assay in 85-year-old women and men. Arch Intern Med 1991; 151:549.
  15. Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994; 331:1249.
  16. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), 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.
  17. Belin RM, Astor BC, Powe NR, Ladenson PW. Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a higher prevalence of mild thyrotropin concentration suppression in the third National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2004; 89:6077.
  18. Meyerovitch J, Rotman-Pikielny P, Sherf M, et al. Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians. Arch Intern Med 2007; 167:1533.
  19. Schouten BJ, Brownlie BE, Frampton CM, Turner JG. Subclinical thyrotoxicosis in an outpatient population - predictors of outcome. Clin Endocrinol (Oxf) 2011; 74:257.
  20. Rosario PW. The natural history of subclinical hyperthyroidism in patients below the age of 65 years. Clin Endocrinol (Oxf) 2008; 68:491.
  21. Rosario PW. Natural history of subclinical hyperthyroidism in elderly patients with TSH between 0.1 and 0.4 mIU/l: a prospective study. Clin Endocrinol (Oxf) 2010; 72:685.
  22. Vadiveloo T, Donnan PT, Cochrane L, Leese GP. The Thyroid Epidemiology, Audit, and Research Study (TEARS): the natural history of endogenous subclinical hyperthyroidism. J Clin Endocrinol Metab 2011; 96:E1.
  23. Das G, Ojewuyi TA, Baglioni P, et al. Serum thyrotrophin at baseline predicts the natural course of subclinical hyperthyroidism. Clin Endocrinol (Oxf) 2012; 77:146.
  24. Ross DS. Hyperthyroidism, thyroid hormone therapy, and bone. Thyroid 1994; 4:319.
  25. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008; 29:76.
  26. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet 2012; 379:1142.
  27. Collet TH, Gussekloo J, Bauer DC, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 2012; 172:799.
  28. Heeringa J, Hoogendoorn EH, van der Deure WM, et al. High-normal thyroid function and risk of atrial fibrillation: the Rotterdam study. Arch Intern Med 2008; 168:2219.
  29. Gammage MD, Parle JV, Holder RL, et al. Association between serum free thyroxine concentration and atrial fibrillation. Arch Intern Med 2007; 167:928.
  30. Vadiveloo T, Donnan PT, Cochrane L, Leese GP. The Thyroid Epidemiology, Audit, and Research Study (TEARS): morbidity in patients with endogenous subclinical hyperthyroidism. J Clin Endocrinol Metab 2011; 96:1344.
  31. Nanchen D, Gussekloo J, Westendorp RG, et al. Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk. J Clin Endocrinol Metab 2012; 97:852.
  32. Gencer B, Collet TH, Virgini V, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation 2012; 126:1040.
  33. Selmer C, Olesen JB, Hansen ML, et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab 2014; 99:2372.
  34. Yavuz DG, Yazici D, Toprak A, et al. Exogenous subclinical hyperthyroidism impairs endothelial function in nodular goiter patients. Thyroid 2008; 18:395.
  35. Dörr M, Robinson DM, Wallaschofski H, et al. Low serum thyrotropin is associated with high plasma fibrinogen. J Clin Endocrinol Metab 2006; 91:530.
  36. Demir T, Akinci B, Comlekci A, et al. Levothyroxine (LT4) suppression treatment for benign thyroid nodules alters coagulation. Clin Endocrinol (Oxf) 2009; 71:446.
  37. Eustatia-Rutten CF, Corssmit EP, Heemstra KA, et al. Autonomic nervous system function in chronic exogenous subclinical thyrotoxicosis and the effect of restoring euthyroidism. J Clin Endocrinol Metab 2008; 93:2835.
  38. Mercuro G, Panzuto MG, Bina A, et al. Cardiac function, physical exercise capacity, and quality of life during long-term thyrotropin-suppressive therapy with levothyroxine: effect of individual dose tailoring. J Clin Endocrinol Metab 2000; 85:159.
  39. Ochs N, Auer R, Bauer DC, et al. Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med 2008; 148:832.
  40. Haentjens P, Van Meerhaeghe A, Poppe K, Velkeniers B. Subclinical thyroid dysfunction and mortality: an estimate of relative and absolute excess all-cause mortality based on time-to-event data from cohort studies. Eur J Endocrinol 2008; 159:329.
  41. van de Ven AC, Netea-Maier RT, de Vegt F, et al. Associations between thyroid function and mortality: the influence of age. Eur J Endocrinol 2014; 171:183.
  42. Flynn RW, Bonellie SR, Jung RT, et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 2010; 95:186.
  43. Kalmijn S, Mehta KM, Pols HA, et al. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study. Clin Endocrinol (Oxf) 2000; 53:733.
  44. Tan ZS, Beiser A, Vasan RS, et al. Thyroid function and the risk of Alzheimer disease: the Framingham Study. Arch Intern Med 2008; 168:1514.
  45. Ceresini G, Lauretani F, Maggio M, et al. Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study. J Am Geriatr Soc 2009; 57:89.
  46. Moon JH, Park YJ, Kim TH, et al. Lower-but-normal serum TSH level is associated with the development or progression of cognitive impairment in elderly: Korean Longitudinal Study on Health and Aging (KLoSHA). J Clin Endocrinol Metab 2014; 99:424.
  47. Roberts LM, Pattison H, Roalfe A, et al. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med 2006; 145:573.
  48. Moon JH, Ahn S, Seo J, et al. The effect of long-term thyroid-stimulating hormone suppressive therapy on the cognitive function of elderly patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 2014; 99:3782.
  49. Samuels MH, Kolobova I, Smeraglio A, et al. The effects of levothyroxine replacement or suppressive therapy on health status, mood, and cognition. J Clin Endocrinol Metab 2014; 99:843.
  50. Schlote B, Schaaf L, Schmidt R, et al. Mental and physical state in subclinical hyperthyroidism: investigations in a normal working population. Biol Psychiatry 1992; 32:48.
  51. Eustatia-Rutten CF, Corssmit EP, Pereira AM, et al. Quality of life in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomized controlled trial. Clin Endocrinol (Oxf) 2006; 64:284.
  52. Samuels MH, Schuff KG, Carlson NE, et al. Health status, mood, and cognition in experimentally induced subclinical thyrotoxicosis. J Clin Endocrinol Metab 2008; 93:1730.
  53. Carr D, McLeod DT, Parry G, Thornes HM. Fine adjustment of thyroxine replacement dosage: comparison of the thyrotrophin releasing hormone test using a sensitive thyrotrophin assay with measurement of free thyroid hormones and clinical assessment. Clin Endocrinol (Oxf) 1988; 28:325.
  54. Biondi B, Palmieri EA, Fazio S, et al. Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients. J Clin Endocrinol Metab 2000; 85:4701.
  55. Casey BM, Dashe JS, Wells CE, et al. Subclinical hyperthyroidism and pregnancy outcomes. Obstet Gynecol 2006; 107:337.
  56. Biondi B, Cooper DS. Benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer. Thyroid 2010; 20:135.
  57. Sgarbi JA, Villaça FG, Garbeline B, et al. The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism in clinical and heart abnormalities. J Clin Endocrinol Metab 2003; 88:1672.
  58. Faber J, Wiinberg N, Schifter S, Mehlsen J. Haemodynamic changes following treatment of subclinical and overt hyperthyroidism. Eur J Endocrinol 2001; 145:391.
  59. Mudde AH, Houben AJ, Nieuwenhuijzen Kruseman AC. Bone metabolism during anti-thyroid drug treatment of endogenous subclinical hyperthyroidism. Clin Endocrinol (Oxf) 1994; 41:421.
  60. Faber J, Jensen IW, Petersen L, et al. Normalization of serum thyrotrophin by means of radioiodine treatment in subclinical hyperthyroidism: effect on bone loss in postmenopausal women. Clin Endocrinol (Oxf) 1998; 48:285.
  61. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004; 291:228.