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ESSENTIALS OF DIAGNOSIS
Sweating, weight loss or gain, anxiety, palpitations, loose stools, heat intolerance, menstrual irregularity.
Tachycardia; warm, moist skin; stare; tremor.
Graves disease: most common cause of hyperthyroidism; palpable goiter (sometimes with bruit) in most patients; ophthalmopathy also common.
Amiodarone: most common cause of thyrotoxic crisis “thyroid storm.”
Suppressed TSH in primary hyperthyroidism; usually increased T4, FT4, T3, FT3.
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GENERAL CONSIDERATIONS
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The term “thyrotoxicosis” refers to the clinical manifestations associated with elevated serum levels of T4 or T3 that are excessive for the individual (hyperthyroidism).
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Graves disease (known as Basedow disease in Europe) is the most common cause of thyrotoxicosis. It is an autoimmune disorder, characterized by an increase in synthesis and release of thyroid hormones. Autoantibodies bind to the TSH receptors in the thyroid cell membranes and stimulate the gland to overproduce thyroid hormones. These autoantibodies are known as thyroid-stimulating immunoglobulins (TSI) or thyrotropin receptor antibodies (TRAb). The presence of the latter antibodies distinguishes Graves disease from autoimmune chronic lymphocytic thyroiditis since in both conditions serum antithyroid antibodies (TPO Ab or Tg Ab or both) are usually present.
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Graves disease is much more common in women than in men (8:1), and its onset is usually between the ages of 20 and 40 years. It may be accompanied by infiltrative ophthalmopathy (Graves exophthalmos) and, less commonly, by infiltrative dermopathy (pretibial myxedema eFigure 26–7). The thymus gland is typically enlarged and serum antinuclear antibody levels are usually elevated. Many patients with Graves disease have a family history of either Graves disease or autoimmune thyroiditis. Histocompatibility studies have shown an association with group HLA-B8 and HLA-DR3.
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Dietary iodine supplementation can trigger Graves disease. An increased incidence of Graves disease occurs in countries that have embarked on national programs to fortify commercial salt with potassium iodide; the increase in Graves disease lasts about 4 years. Similarly, patients being treated with potassium iodide or amiodarone (which contains iodine) have an increased risk of developing Graves disease.
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Chemotherapy with immune checkpoint inhibitors (ipilimumab, pembrolizumab, tremelimumab, and atezolizumab) and alemtuzumab (for multiple sclerosis) can both precipitate Graves disease and cause hyperthyroidism from destructive autoimmune thyroiditis (silent thyroiditis).
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Patients with Graves disease have an increased risk of other systemic autoimmune disorders, including Sjögren syndrome, celiac disease, pernicious anemia, Addison disease, alopecia areata, vitiligo, type 1 diabetes mellitus, hypoparathyroidism, myasthenia gravis, and cardiomyopathy.
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B. Toxic Multinodular Goiter and Thyroid Nodules
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Autonomous hyperfunctioning thyroid nodules that produce hyperthyroidism are known as toxic multinodular goiter (Plummer disease) and are more prevalent among older adults and in iodine-deficient regions. A single hyperfunctioning nodule ...