Disorders that cause hyperthyroidism
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
Several different disorders can cause hyperthyroidism. It is essential that the correct cause be identified because appropriate therapy depends upon the underlying mechanism of the hyperthyroidism. From a pathogenetic viewpoint, hyperthyroidism results from two different mechanisms that can be distinguished by the findings on the 24-hour radioiodine uptake (table 1):
●Hyperthyroidism with a normal or high radioiodine uptake indicates de novo synthesis of hormone. These disorders can be treated with a thionamide, such as methimazole, which will interfere with hormone synthesis. (See "Thionamides in the treatment of Graves' disease".)
●Hyperthyroidism with a near absent radioiodine uptake indicates either inflammation and destruction of thyroid tissue with release of preformed hormone into the circulation or an extrathyroidal source of thyroid hormone. Thyroid hormone is not being actively synthesized when hyperthyroidism is due to thyroid inflammation; as a result, thionamide therapy is not useful in these disorders.
This topic will review the main causes of hyperthyroidism and outline the therapeutic approach to the less common conditions. The treatment of Graves' disease and toxic nodular goiter and the diagnostic approach to patients with hyperthyroidism are discussed separately. (See "Diagnosis of hyperthyroidism".)
Hyperthyroidism is more common in women than men (5:1 ratio). The overall prevalence of hyperthyroidism, which is approximately 1.3 percent, increases to 4 to 5 percent in older women . Hyperthyroidism is also more common in smokers . Graves' disease is seen most often in younger women, while toxic nodular goiter is more common in older women.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- 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.
- Asvold BO, Bjøro T, Nilsen TI, Vatten LJ. Tobacco smoking and thyroid function: a population-based study. Arch Intern Med 2007; 167:1428.
- Holm IA, Manson JE, Michels KB, et al. Smoking and other lifestyle factors and the risk of Graves' hyperthyroidism. Arch Intern Med 2005; 165:1606.
- Brent GA. Clinical practice. Graves' disease. N Engl J Med 2008; 358:2594.
- Davies TF. New thinking on the immunology of Graves' disease. Thyroid Today 1992; 15:1.
- Radosavljević VR, Janković SM, Marinković JM. Stressful life events in the pathogenesis of Graves' disease. Eur J Endocrinol 1996; 134:699.
- Laurberg P, Pedersen KM, Vestergaard H, Sigurdsson G. High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland. J Intern Med 1991; 229:415.
- McDermott MT, Burman KD, Hofeldt FD, Kidd GS. Lithium-associated thyrotoxicosis. Am J Med 1986; 80:1245.
- Carella C, Mazziotti G, Amato G, et al. Clinical review 169: Interferon-alpha-related thyroid disease: pathophysiological, epidemiological, and clinical aspects. J Clin Endocrinol Metab 2004; 89:3656.
- Daniels GH, Vladic A, Brinar V, et al. Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis. J Clin Endocrinol Metab 2014; 99:80.
- Fatourechi V, McConahey WM, Woolner LB. Hyperthyroidism associated with histologic Hashimoto's thyroiditis. Mayo Clin Proc 1971; 46:682.
- Duprez L, Hermans J, Van Sande J, et al. Two autonomous nodules of a patient with multinodular goiter harbor different activating mutations of the thyrotropin receptor gene. J Clin Endocrinol Metab 1997; 82:306.
- Parma J, Duprez L, Van Sande J, et al. Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. J Clin Endocrinol Metab 1997; 82:2695.
- Holzapfel HP, Führer D, Wonerow P, et al. Identification of constitutively activating somatic thyrotropin receptor mutations in a subset of toxic multinodular goiters. J Clin Endocrinol Metab 1997; 82:4229.
- Pinducciu C, Borgonovo G, Arezzo A, et al. Toxic thyroid adenoma: absence of DNA mutations of the TSH receptor and Gs alpha. Eur J Endocrinol 1998; 138:37.
- Führer D, Holzapfel HP, Wonerow P, et al. Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules. J Clin Endocrinol Metab 1997; 82:3885.
- Kopp P, Muirhead S, Jourdain N, et al. Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor. J Clin Invest 1997; 100:1634.
- Yoshimura M, Pekary AE, Pang XP, et al. Thyrotropic activity of basic isoelectric forms of human chorionic gonadotropin extracted from hydatidiform mole tissues. J Clin Endocrinol Metab 1994; 78:862.
- Wynne AG, Gharib H, Scheithauer BW, et al. Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients. Am J Med 1992; 92:15.
- Beck-Peccoz P, Brucker-Davis F, Persani L, et al. Thyrotropin-secreting pituitary tumors. Endocr Rev 1996; 17:610.
- Losa M, Giovanelli M, Persani L, et al. Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab 1996; 81:3084.
- Chanson P, Weintraub BD, Harris AG. Octreotide therapy for thyroid-stimulating hormone-secreting pituitary adenomas. A follow-up of 52 patients. Ann Intern Med 1993; 119:236.
- Golsman, J, Wietecha, K, Rock, J. Thyrotropin-secreting pituitary adenoma: Reduction of tumor size by octreotide therapy into the sellar confines allows surgical cure by transsphenoidal hypophysectomy. 10th Internat Cong Endocrinol, San Francisco, 12-15 June 1996, abst. no. P2-482.
- Rösler A, Litvin Y, Hage C, et al. Familial hyperthyroidism due to inappropriate thyrotropin secretion successfully treated with triiodothyronine. J Clin Endocrinol Metab 1982; 54:76.
- Beck-Peccoz P, Piscitelli G, Cattaneo MG, Faglia G. Successful treatment of hyperthyroidism due to nonneoplastic pituitary TSH hypersecretion with 3,5,3'-triiodothyroacetic acid (TRIAC). J Endocrinol Invest 1983; 6:217.
- Duprez L, Parma J, Van Sande J, et al. Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. Nat Genet 1994; 7:396.
- Farid NR, Kascur V, Balazs C. The human thyrotropin receptor is highly mutable: a review of gain-of-function mutations. Eur J Endocrinol 2000; 143:25.
- Tamada D, Onodera T, Kitamura T, et al. Hyperthyroidism due to thyroid-stimulating hormone secretion after surgery for Cushing's syndrome: a novel cause of the syndrome of inappropriate secretion of thyroid-stimulating hormone. J Clin Endocrinol Metab 2013; 98:2656.
- Chadha C, Pritzker M, Mariash CN. Effect of epoprostenol on the thyroid gland: enlargement and secretion of thyroid hormone. Endocr Pract 2009; 15:116.
- Trapp CM, Elder RW, Gerken AT, et al. Pediatric pulmonary arterial hypertension and hyperthyroidism: a potentially fatal combination. J Clin Endocrinol Metab 2012; 97:2217.
- Volpé R. Subacute (de Quervain's) thyroiditis. Clin Endocrinol Metab 1979; 8:81.
- Nikolai TF, Coombs GJ, McKenzie AK, et al. Treatment of lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (silent thyroiditis). Arch Intern Med 1982; 142:2281.
- Roti E, Emerson CH. Clinical review 29: Postpartum thyroiditis. J Clin Endocrinol Metab 1992; 74:3.
- Lambert M, Unger J, De Nayer P, et al. Amiodarone-induced thyrotoxicosis suggestive of thyroid damage. J Endocrinol Invest 1990; 13:527.
- Grossmann M, Premaratne E, Desai J, Davis ID. Thyrotoxicosis during sunitinib treatment for renal cell carcinoma. Clin Endocrinol (Oxf) 2008; 69:669.
- Ahmadieh H, Salti I. Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment. Biomed Res Int 2013; 2013:725410.
- Volpé R. The management of subacute (DeQuervain's) thyroiditis. Thyroid 1993; 3:253.
- Arem R, Munipalli B. Ipodate therapy in patients with severe destruction-induced thyrotoxicosis. Arch Intern Med 1996; 156:1752.
- HYPERTHYROIDISM WITH A NORMAL OR HIGH RADIOIODINE UPTAKE
- Graves' disease
- Toxic adenoma and toxic multinodular goiter
- Iodine-induced hyperthyroidism
- Trophoblastic disease and germ cell tumors
- TSH-mediated hyperthyroidism
- HYPERTHYROIDISM WITH A NEAR ABSENT RADIOIODINE UPTAKE
- Exogenous and ectopic hyperthyroidism
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS