Overview and Risk Factors
Hyperthyroidism is a condition of excess thyroid hormone. It may be caused by intrinsic thyroid dysfunction (primary hyperthyroidism) or by excessive stimulation of the thyroid gland by an autonomous source of thyroid-stimulating hormone (TSH, secondary hyperthyroidism). Hyperthyroidism may also be caused by excessive ingestion of exogenous thyroid hormone.
Approximately 85% of cases of primary hyperthyroidism result from Graves' disease, in which autoantibodies to the TSH receptor continually stimulate the thyroid gland to overproduce thyroid hormone. Other causes of primary hyperthyroidism include toxic adenoma, toxic multinodular goiter, and thyroiditis. Secondary hyperthyroidism is usually caused by a TSH-secreting anterior pituitary adenoma. Hyperthyroidism may be associated with autoimmune diseases, including Addison's disease and type 1 diabetes mellitus.
Clinical manifestations of hyperthyroidism vary significantly. The most common signs and symptoms include tachycardia, palpitations, heat intolerance, weight loss, and menstrual irregularities. Less common are nausea, vomiting, restlessness, anxiety, tremor, and atrial fibrillation. Further signs and symptoms depend on the etiology and severity of hyperthyroidism. In Graves' disease, for example, typical symptoms are a diffuse, symmetric goiter; ophthalmopathy (including lid lag and irreversible exophthalmos); and dermopathy (including pretibial myxedema, a thickening and redness of the pretibial skin).
The most severe form of hyperthyroidism is thyroid storm, which can be precipitated by thyroidectomy, acute stress (eg, infection, trauma, nonthyroid surgery), or an acute iodine load. Presentation may include extreme fever (up to 40ºC-41ºC/104ºF-106ºF), severe nausea, vomiting, jaundice, rigidity, agitation, or delirium; these symptoms may progress to seizures and coma, tachycardia, and congestive heart failure, and frank shock.
Hyperthyroidism is more common in females. There may also be a genetic component of risk, as individuals with certain HLA-D subtypes have an increased risk for Graves' disease.
Diagnosis and Treatment
TSH is the most cost-effective assay for hyperthyroidism and should be the initial screening test. TSH is decreased in primary hyperthyroidism. Elevated (or sometimes normal) TSH levels alongside elevated thyroxine (T4) or triiodothyronine (T3) levels suggest secondary hyperthyroidism.
Free T4 concentration is increased; the magnitude of T4 elevation is correlated with the degree of biochemical disease.
Once hyperthyroidism has been diagnosed, further testing can determine the underlying etiology. Antithyroglobulin and antithyroid peroxidase antibodies may be present in Graves' disease. A 24-hour radioactive iodine uptake scan is often necessary for diagnosis of Graves' disease and exclusion of other disorders. Uptake is increased in Graves' disease, toxic adenoma, and multinodular goiter, and is decreased in thyroiditis, excessive iodine consumption, and overmedication with thyroid hormone supplementation.
Radioimaging can define the shape and size of the thyroid and determine where "hot" nodules are distributed (iodine will concentrate in "hot" nodules). Functional nodules may represent toxic adenoma or multinodular goiter. Diffuse uptake is seen in Graves' disease.
Initial therapy often uses a beta-blocker to oppose the adrenergic effects of thyroid hormone.
Antithyroid drugs (eg, propylthiouracil, methimazole) interfere with thyroid hormone production. Although antithyroid drugs must generally be continued for at least 1 to 2 years, they may be a useful temporizing measure in anticipation of spontaneous remission of hyperthyroidism.
Radioactive iodine (I131) to ablate thyroid tissue is a definitive treatment with excellent success rates; it is the most commonly used treatment. It cannot, however, be used in pregnancy.
Surgical removal of the thyroid (thyroidectomy) is also an effective treatment. It is often indicated in hyperthyroid patients who have an obstructive goiter.
Lifelong thyroid hormone supplementation will be necessary after ablation or thyroidectomy due to resultant hypothyroidism.
Thyroid storm treatment is generally similar to that for hyperthyroidism, but with closer monitoring and higher medication doses. Treatment with glucocorticoids or potassium iodine may be indicated. Intensive care unit observation is essential.
Relationships between diet and hyperthyroidism relate to celiac disease and to excessive iodine intake. Patients with celiac disease have an increased prevalence of autoimmune disease, including Graves' disease.1 It is unclear whether the association is due to a common genetic basis for the two conditions2 or to an as-yet unidentified cause-and-effect relationship. Some have suggested that hyperthyroidism in celiac disease may relate to an autoantibody-induced stimulation of thyroid hormone output.3 Limited evidence indicates that antithyroid antibody production abates in celiac patients after 3 to 6 months on a gluten-free diet.4
Iodine-induced hyperthyroidism has been reported in patients in remission after treatment for previous thyroid diseases. For example, euthyroid patients previously treated with antithyroid drugs for Graves' disease are prone to develop iodine-induced hyperthyroidism.5 Remission rates for Graves' disease after treatment with antithyroid medication may be related to excess iodine intake.6,7 However, this has not been established in controlled clinical trials.
A gluten-free diet may be tried prospectively.
What to Tell the Family
Hyperthyroidism is common and generally responds well to medical therapy. In some cases, the disease spontaneously remits. In others, radioactive iodine therapy is indicated to remove or destroy overactive thyroid cells, necessitating lifelong thyroid hormone replacement to maintain a normal hormone level. Patients should attempt a trial period of avoiding foods that contain high concentrations of iodine, including iodized salt, sea salt, seafood, dairy products, and eggs, and foods that contain iodides, iodate, algin, alginates, carrageen, agar, and red dye number 3.
2. Ch'ng CL, Biswas M, Benton A, Jones MK, Kingham JG. Prospective screening for coeliac disease in patients with Graves' hyperthyroidism using anti-gliadin and tissue transglutaminase antibodies. Clin Endocrinol (Oxf). 2005;62:303-306.
3. Daly P. Thyroid Disease: Why Do Celiacs Have It? Celiac Sprue Association, 2004. Available at: www.csaceliacs.org/library/whythyroid.php. Accessed May 6, 2006.
6. Garcia-Mayor RV, Paramo C, Luna Cano R, Perez Mendez LF, Galofre JC, Andrade A. Antithyroid drug and Graves' hyperthyroidism. Significance of treatment duration and TRAb determination on lasting remission. J Endocrinol Invest. 1992;15:815-820.