Diagnosis of hyperthyroidism
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
The diagnosis of hyperthyroidism is usually evident in patients with unequivocal clinical and biochemical manifestations of the disease. Other patients have fewer and less obvious clinical signs but definite biochemical hyperthyroidism. Still others have little or no clinical hyperthyroidism, and their only biochemical abnormality is a low serum thyroid-stimulating hormone (TSH) concentration, a disorder called subclinical hyperthyroidism.
Following a brief discussion of the clinical manifestations of hyperthyroidism, the diagnosis and evaluation of patients with hyperthyroidism will be presented here. An overview of the clinical manifestations of hyperthyroidism, disorders that cause hyperthyroidism, the diagnosis of hyperthyroidism during pregnancy, and subclinical hyperthyroidism are discussed in detail separately. (See "Overview of the clinical manifestations of hyperthyroidism in adults" and "Disorders that cause hyperthyroidism" and "Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes" and "Subclinical hyperthyroidism in nonpregnant adults".)
Overt hyperthyroidism — Most patients with overt hyperthyroidism have a dramatic constellation of symptoms. These symptoms characteristically include anxiety, emotional lability, weakness, tremor, palpitations, heat intolerance, increased perspiration, and weight loss despite a normal or increased appetite [1,2].
While the combination of weight loss and increased appetite is a characteristic finding, some patients gain weight, in particular younger patients, due to excessive appetite stimulation . Other symptoms that may be present include hyperdefecation (not diarrhea), urinary frequency, oligomenorrhea or amenorrhea in women, and gynecomastia and erectile dysfunction in men [3,4]. (See "Overview of the clinical manifestations of hyperthyroidism in adults".)
Milder symptoms — Patients with mild hyperthyroidism and older patients often have symptoms that are referable to one or only a few organ systems . Isolated symptoms and signs that should lead to evaluation for hyperthyroidism in patients of any age include unexplained weight loss, new onset atrial fibrillation, myopathy, menstrual disorders, and gynecomastia.
- Nordyke RA, Gilbert FI Jr, Harada AS. Graves' disease. Influence of age on clinical findings. Arch Intern Med 1988; 148:626.
- Trzepacz PT, Klein I, Roberts M, et al. Graves' disease: an analysis of thyroid hormone levels and hyperthyroid signs and symptoms. Am J Med 1989; 87:558.
- Krassas GE, Pontikides N, Kaltsas T, et al. Menstrual disturbances in thyrotoxicosis. Clin Endocrinol (Oxf) 1994; 40:641.
- Kidd GS, Glass AR, Vigersky RA. The hypothalamic-pituitary-testicular axis in thyrotoxicosis. J Clin Endocrinol Metab 1979; 48:798.
- Trivalle C, Doucet J, Chassagne P, et al. Differences in the signs and symptoms of hyperthyroidism in older and younger patients. J Am Geriatr Soc 1996; 44:50.
- Woeber KA. Thyrotoxicosis and the heart. N Engl J Med 1992; 327:94.
- Ayres J, Rees J, Clark TJ, Maisey MN. Thyrotoxicosis and dyspnoea. Clin Endocrinol (Oxf) 1982; 16:65.
- Boelaert K, Torlinska B, Holder RL, Franklyn JA. Older subjects with hyperthyroidism present with a paucity of symptoms and signs: a large cross-sectional study. J Clin Endocrinol Metab 2010; 95:2715.
- Davey RX, Clarke MI, Webster AR. Thyroid function testing based on assay of thyroid-stimulating hormone: assessing an algorithm's reliability. Med J Aust 1996; 164:329.
- Laurberg P, Vestergaard H, Nielsen S, et al. Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases. J Clin Endocrinol Metab 2007; 92:2149.
- Figge J, Leinung M, Goodman AD, et al. The clinical evaluation of patients with subclinical hyperthyroidism and free triiodothyronine (free T3) toxicosis. Am J Med 1994; 96:229.
- Caplan RH, Pagliara AS, Wickus G. Thyroxine toxicosis. A common variant of hyperthyroidism. JAMA 1980; 244:1934.
- Bambini G, Aghini-Lombardi F, Rosner W, et al. Serum sex hormone-binding globulin in amiodarone-treated patients. A marker for tissue thyrotoxicosis. Arch Intern Med 1987; 147:1781.
- 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, Chatterjee VK. The variable clinical phenotype in thyroid hormone resistance syndrome. Thyroid 1994; 4:225.
- Spencer C, Eigen A, Shen D, et al. Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. Clin Chem 1987; 33:1391.
- 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.
- Lewis GF, Alessi CA, Imperial JG, Refetoff S. Low serum free thyroxine index in ambulating elderly is due to a resetting of the threshold of thyrotropin feedback suppression. J Clin Endocrinol Metab 1991; 73:843.
- Mariotti S, Barbesino G, Caturegli P, et al. Complex alteration of thyroid function in healthy centenarians. J Clin Endocrinol Metab 1993; 77:1130.
- Barbesino G. Misdiagnosis of Graves' Disease with Apparent Severe Hyperthyroidism in a Patient Taking Biotin Megadoses. Thyroid 2016; 26:860.
- Sharma A, Baumann NA, Shah P. Biotin-Induced Biochemical Graves Disease: A Teachable Moment. JAMA Intern Med 2017; 177:571.
- Lytton SD, Kahaly GJ. Bioassays for TSH-receptor autoantibodies: an update. Autoimmun Rev 2010; 10:116.
- Barbesino G, Tomer Y. Clinical review: Clinical utility of TSH receptor antibodies. J Clin Endocrinol Metab 2013; 98:2247.
- Chen JJ, Ladenson PW. Discordant hypothyroxinemia and hypertriiodothyroninemia in treated patients with hyperthyroid Graves' disease. J Clin Endocrinol Metab 1986; 63:102.
- Amino N, Yabu Y, Miki T, et al. Serum ratio of triiodothyronine to thyroxine, and thyroxine-binding globulin and calcitonin concentrations in Graves' disease and destruction-induced thyrotoxicosis. J Clin Endocrinol Metab 1981; 53:113.
- Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016; 26:1343.
- Bahn Chair RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011; 21:593.
- Vos XG, Smit N, Endert E, et al. Frequency and characteristics of TBII-seronegative patients in a population with untreated Graves' hyperthyroidism: a prospective study. Clin Endocrinol (Oxf) 2008; 69:311.
- Izumi Y, Hidaka Y, Tada H, et al. Simple and practical parameters for differentiation between destruction-induced thyrotoxicosis and Graves' thyrotoxicosis. Clin Endocrinol (Oxf) 2002; 57:51.
- Ota H, Amino N, Morita S, et al. Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves' disease. Clin Endocrinol (Oxf) 2007; 67:41.
- CLINICAL MANIFESTATIONS
- - Overt hyperthyroidism
- - Milder symptoms
- - Older patients
- Physical examination
- - Thyroid size
- Laboratory tests
- - Thyroid function tests
- - Other
- Overt hyperthyroidism
- Subclinical hyperthyroidism
- TSH-induced hyperthyroidism
- Critically ill patients
- DIFFERENTIAL DIAGNOSIS
- Euthyroid hyperthyroxinemia
- Low serum TSH without hyperthyroidism
- Assay interference with biotin ingestion
- DETERMINING THE ETIOLOGY
- Our approach
- - Thyroid tests
- - Radioiodine uptake
- - Thyrotropin receptor antibodies
- - Other tests
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS