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Thyrotoxicosis is defined as the state of thyroid hormone excess and is not synonymous with hyperthyroidism, which is the result of excessive thyroid function. However, the major etiologies of thyrotoxicosis are hyperthyroidism caused by Graves’ disease, toxic multinodular goiter (MNG), and toxic adenomas. Other causes are listed in Table 377-1.

TABLE 377-1Causes of Thyrotoxicosis



Graves’ disease accounts for 60–80% of thyrotoxicosis. The prevalence varies among populations, reflecting genetic factors and iodine intake (high iodine intake is associated with an increased prevalence of Graves’ disease). Graves’ disease occurs in up to 2% of women but is one-tenth as frequent in men. The disorder rarely begins before adolescence and typically occurs between 20 and 50 years of age; it also occurs in the elderly.


As in autoimmune hypothyroidism, a combination of environmental and genetic factors, including polymorphisms in HLA-DR, the immunoregulatory genes CTLA-4, CD25, PTPN22, FCRL3, and CD226, as well as the gene encoding the thyroid-stimulating hormone receptor (TSH-R), contributes to Graves’ disease susceptibility. The concordance for Graves’ disease in monozygotic twins is 20–30%, compared to <5% in dizygotic twins. Indirect evidence suggests that stress is an important environmental factor, presumably operating through neuroendocrine effects on the immune system. Smoking is a minor risk factor for Graves’ disease and a major risk factor for the development of ophthalmopathy. Sudden increases in iodine intake may precipitate Graves’ disease, and there is a threefold increase in the occurrence of Graves’ disease in the postpartum period. Graves’ disease may occur during the immune reconstitution phase after highly active antiretroviral therapy (HAART) or alemtuzumab treatment.

The hyperthyroidism of Graves’ disease is caused by thyroid-stimulating immunoglobulin (TSI) that are synthesized in the thyroid gland as well as in bone marrow and lymph nodes. Such antibodies can be detected by bioassays or by using the more widely available thyrotropin-binding inhibitory immunoglobulin (TBII) assays. The presence of TBII in a patient with thyrotoxicosis implies the existence of TSI, and these assays are useful in monitoring pregnant Graves’ patients in whom high levels of TSI can cross ...

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