Disorders that cause hyperthyroidism

Disorders that cause hyperthyroidismAuthorDouglas S Ross, MDSection EditorDavid S Cooper, MDDeputy EditorJean E Mulder, MDDisclosuresAll topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Oct 2012. | This topic last updated: May 22, 2012.

INTRODUCTION — 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".)

EPIDEMIOLOGY — 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 [1]. Hyperthyroidism is also more common in smokers [2]. Graves' disease is seen most often in younger women, while toxic nodular goiter is more common in older women.

In one prospective cohort study of adult women, the overall incidence of Graves' disease was 4.6 per 1000 during 10 years of observation [3].

HYPERTHYROIDISM WITH A NORMAL OR HIGH RADIOIODINE UPTAKE — Autoimmune thyroid disease and autonomous thyroid tissue are the major causes of excess new hormone synthesis by the thyroid.

Graves' disease — Graves' disease is the most common cause of hyperthyroidism [4]. It is an autoimmune disorder resulting from thyrotropin (TSH)-receptor antibodies (also called thyroid-stimulating immunoglobulins), which stimulate thyroid gland growth and thyroid hormone synthesis and release [5]. Stressful life events may be a risk factor for the disease [6]. Another risk factor may be a relatively high iodine intake [7]. Ophthalmopathy and pretibial myxedema are additional autoimmune manifestations of Graves' disease. (See "Pathogenesis of Graves' disease".)