Thyrotoxicosis can has a broad spectrum of etiologies (Table I). While it is most commonly caused by Graves' disease, it is of importance to recognize other etiologies in order to choose the most appropriate therapeutic option and long-term surveillance. Toxic adenomas are characterized by a single hyperactive nodule in the thyroid leading to clinical and biochemical thyrotoxicosis. Autonomous or toxic adenomas are most commonly caused by somatic gain-of-function mutations in the TSH receptor or the stimulatory Gs alpha subunit. A toxic adenoma is readily recognized on a thyroid scan. Toxic adenomas appear to be more common in countries with a low iodine intake. The possibility of developing thyrotoxicosis in a patient with a hot nodule with a diameter of 3 cm or larger is 20% in 6 years. This risk is substantially less in smaller nodules. Older patients with a hot nodule are more likely to become toxic as compared to younger patients. Definitive treatment consists in the administration of 131iodine, surgical removal of the nodule, or, less commonly used, percutaneous ethanol injection. The likelihood of malignancy in a toxic nodule is very low. In multinodular goiters, several nodules display an autonomous function. The pathogenesis is complex but may also include activating TSH receptor mutations. In addition to hyperthyroidism, some patients present with compressive signs. The diagnostic and therapeutic approach is in general similar to patients with a toxic adenoma, but may need cross-sectional imaging and pulmonary function tests in some patients. Therapeutically, surgery and radioiodine therapy are the most commonly used modalities. Well-differentiated thyroid carcinomas are only rarely associated with thyrotoxicosis. Treatment of patients with functioning thyroid carcinomas does not differ from the therapy of thyroid cancer patients without thyrotoxicosis, but appropriate control of the hyperthyroid state with antithyroid drugs and beta-blockers is important before submitting a patient to thyroid surgery or 131iodine therapy. Familial and sporadic forms of non-autoimmune hyperthyroidism are uncommon. They are caused by inherited or de novo germline gain-of-function mutations in the TSH receptor. Inappropriate TSH secretion by a TSH-secreting pituitary tumor is a rare cause of hyperthyroidism. Transsphenoidal surgery, in combination with radiotherapy and somatostatin analogues in some patients, are the therapies of choice. During pregnancy, transient gestational thyrotoxicosis may be due to stimulation of the TSH receptor by high levels of hCG. In a single instance, a mutation in the TSH receptor conferring hypersensitivity to hCG has been reported. Hydatiform moles or a choriocarcinomas can lead to high hCG levels and thyrotoxicosis. Hydatiform moles are treated by suction. Choriocarcinomas can now be treated successfully in most patients with chemotherapy. Struma ovarii, thyroid tissue in a ovarian teratoma, rarely causes hyperthyroidism. Most patients with struma ovarii are clinically and biochemically euthyroid. Treatment consists of surgical removal of the teratoma. Administration of moderate or high doses of iodine may induce thyrotoxicosis in patients with or without apparent pre-existing thyroid disease. There are numerous sources of iodine, for example drugs, contrast agents, disinfectants, and food components. A notorious iodine-containing agent is the anti-arrhythmic drug amiodarone, which may induce thyrotoxicosis because of its high iodine content and/or a drug-induced thyroiditis. Any form of thyroiditis can be associated with a thyrotoxic phase because the disruption of thyroid follicles can result in an increased release …