Graves' Disease – Top USMLE Diseases

Graves' disease is an autoimmune disorder characterized by the presence of circulating thyroid-stimulating hormone (TSH) receptor antibodies, which cause the thyroid gland to hyperfunction. Clinical features include those of hyperthyroidism, as well as orbitopathy, goiter, and dermopathy/pretibial myxedema. Diagnosis is by thyroid laboratory tests showing a low TSH, elevated thyroid hormones (thyroxine (T4) and triiodothyronine (T3)) and thyrotropin-receptor antibodies (TRAbs; particularly the thyroid-stimulating immunoglobulins subtype). If initial tests are nondiagnostic, radioactive iodine uptake (increased uptake) and thyroid ultrasound (diffuse thyroid enlargement) provide diagnostic information. Treatment options include antithyroid drugs, radioiodine ablation, and surgery.

Graves' disease is an autoimmune disorder characterized by the presence of circulating thyroid-stimulating hormone (TSH) receptor antibodies, which cause the thyroid gland to hyperfunction. Clinical features include those of hyperthyroidism, as well as orbitopathy, goiter, and dermopathy/pretibial myxedema. Diagnosis is by thyroid laboratory tests showing a low TSH, elevated thyroid hormones (thyroxine (T4) and triiodothyronine (T3)) and thyrotropin-receptor antibodies (TRAbs; particularly the thyroid-stimulating immunoglobulins subtype). If initial tests are nondiagnostic, radioactive iodine uptake (increased uptake) and thyroid ultrasound (diffuse thyroid enlargement) provide diagnostic information. Treatment options include antithyroid drugs, radioiodine ablation, and surgery.

Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non–iodine-deficient regions. Primary hypothyroidism occurs with thyroid gland disorders, while the central type arises from pituitary and hypothalamic conditions. Thyroid hormones are integral in metabolic processes and in the development of the brain and other organs. Congenital hypothyroidism can result in significant mental disability due to the loss of thyroid hormones. The features of acquired hypothyroidism also reflect the effects of slowed organ function, such as fatigue, bradycardia, cold intolerance, and exertional dyspnea. Diagnosis is by thyroid function testing. Elevated thyroid stimulating hormone and low free thyroxine (T4) levels are noted. Treatment is with synthetic T4.

Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves’ disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Subacute thyroiditis is an example of thyrotoxicosis without hyperthyroidism, and a pituitary adenoma, which secretes thyroid-stimulating hormone (TSH) is an example of secondary hyperthyroidism. Clinical features of thyrotoxicosis are mostly due to an increase in the metabolic rate and overactivity of the sympathetic nervous system (i.e., an increase in the β-adrenergic “tone”). Thyrotoxicosis is diagnosed by measuring the levels of TSH produced by the anterior pituitary gland and free T4 and T3. Depending on the etiology and clinical presentation, it may be treated pharmacologically, surgically, or with radioiodine.

Graves' disease is an autoimmune disorder characterized by the presence of circulating antibodies against the thyroid-stimulating hormone (TSH) receptors, thereby causing the thyroid gland to hyperfunction. Clinical features include hyperthyroidism (of which Graves' disease is the most common cause), orbitopathy, goiter, and dermopathy/pretibial myxedema. Manifestations reflect the muti-systemic effects of a hyperactive thyroid, including heat intolerance, sweating, palpitations, tremors, pretibial myxedema, and exophthalmos. Diagnosis is by thyroid laboratory tests showing a low TSH, elevated thyroid hormones (thyroxine (T4) and triiodothyronine (T3)) and thyrotropin-receptor antibodies (particularly the thyroid-stimulating immunoglobulins subtype). If initial tests are nondiagnostic, radioactive iodine uptake (increased uptake) and thyroid ultrasound (diffuse thyroid enlargement) provide diagnostic information. Treatment options include thionamides, radioiodine ablation, and surgery.

Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Common side effects among the disease-modifying antirheumatic drugs include bone marrow suppression and hepatotoxicity. Leflunomide, methotrexate, and tumor necrosis factor (TNF)-ɑ inhibitors are avoided in pregnancy due to their potential teratogenicity. Hydroxychloroquine and sulfasalazine are safe for use during pregnancy.

The abdominal examination is the portion of the physical exam evaluating the abdomen for signs of disease. The abdominal examination consists of inspection, auscultation, percussion, and palpation. Along with information from the history, the information gathered from the physical examination of the abdomen is used by the physician to generate a differential diagnosis and treatment plan for the patient.

Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Common side effects include GI irritation, prolonged bleeding, and AKI.

Antithyroid agents are used in the management of hyperthyroidism, particularly that due to Graves’ disease. This group of medications includes the thionamides (methimazole and propylthiouracil), potassium iodide, and radioactive iodine. Thionamides are currently the preferred choice for hyperthyroid management; these drugs work by blocking thyroid hormone synthesis. Propylthiouracil also blocks the conversion of T4 to T3 and, because it less readily crosses the placenta, is the preferred therapy in the 1st trimester of pregnancy. Potassium iodide mainly works through inhibiting thyroid hormone release. Potassium iodide is most often used as a pretreatment prior to thyroid surgery or as an adjunct to hyperthyroid management. Radioactive iodine causes damage to thyroid tissue, thereby definitively reducing thyroid function.

Autoimmunity is a pathologic immune response toward self-antigens, resulting from a combination of factors: immunologic, genetic, and environmental. The immune system is equipped with self-tolerance, allowing immune cells such as T cells and B cells to recognize self-antigens and to not mount a reaction against them. Defects in this mechanism, along with environmental triggers (such as infections) and genetic susceptibility factors (most notable of which are the HLA genes) can lead to autoimmune diseases. These conditions are more commonly seen in women. Autoimmune diseases are chronic, with clinical manifestations consistent with the associated immune response. Among these conditions are Graves’ disease (autoantibodies against thyroid hormone receptors), myasthenia gravis (antibodies against acetylcholine receptors), type 1 diabetes (pancreatic β-cell destruction by immune cells), and systemic lupus erythematosus (multiorgan damage driven by immune complexes and autoantibodies).

Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves’ disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Subacute thyroiditis is an example of thyrotoxicosis without hyperthyroidism, and a pituitary adenoma, which secretes thyroid-stimulating hormone (TSH) is an example of secondary hyperthyroidism. Clinical features of thyrotoxicosis are mostly due to an increase in the metabolic rate and overactivity of the sympathetic nervous system (i.e., an increase in the β-adrenergic “tone”). Thyrotoxicosis is diagnosed by measuring the levels of TSH produced by the anterior pituitary gland and unbound T4 and T3. Depending on the etiology and clinical presentation, it may be treated pharmacologically, surgically, or with radioiodine.

Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non–iodine-deficient regions. Primary hypothyroidism occurs with thyroid gland disorders, while the central type arises from pituitary and hypothalamic conditions. Thyroid hormones are integral in metabolic processes and in the development of the brain and other organs. Congenital hypothyroidism can result in significant mental disability due to the loss of thyroid hormones. The features of acquired hypothyroidism also reflect the effects of slowed organ function, such as fatigue, bradycardia, cold intolerance, and exertional dyspnea. Diagnosis is by thyroid function testing. Elevated thyroid stimulating hormone and low free thyroxine (T4) levels are noted. Treatment is with synthetic T4.