Diagnosis and management of thyrotoxicosis.

What is the underlying pathophysiology of thyrotoxicosis? Graves’ disease is an autoimmune disease mediated by antibodies that stimulate the thyroid stimulating hormone (TSH) receptor, leading to excess secretion of thyroid hor­ mones and hyperplasia of thyroid follicular cells, resulting in hyperthyroidism and diffuse goitre (table 1). Both genetic and environmental factors (for example, smoking, stress, and dietary iodine) play important roles in the pathogenesis of Graves’ disease. Hyperthyroidism in solitary toxic nodule and toxic multi­ nodular goitres results from over­secretion of thyroid hor­ mones by one or more nodules. Histologically these nodules are benign follicular adenomas. Thyroiditis (subacute, silent, or post partum) causes release of preformed thyroid hormones into the circulation as a result of inflammatory destruction of the thyroid follicles, resulting in transient thyrotoxicosis. Gestational hyperthyroidism occurs in the first trimester of pregnancy owing to increased secretion of thyroid hormone in response to placental β human chorionic gonadotrophin, which is structurally similar to TSH. Gestational hyperthy­ roidism is particularly common in women with hyperemesis gravidarum, which is associated with high levels of β human chorionic gonadotrophin. Several drugs, including amiodarone, iodine, lithium, interferon α, highly active retroviral therapy, tyrosine kinase inhibitors, and levothyroxine can cause thyrotoxicosis in d ifferent ways (table 1).