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A. Primary hyperthyroidism (Grave's disease).

• Thyrotoxicosis is a clinical syndrome that occurs when tissues are exposed to high levels of thyroid hormone, also known as hyperthyroidism.
• The most common cause of thyrotoxicosis is Graves' disease, a type of primary hyperthyroidism. Graves' disease is an autoimmune condition in which an antibody (IgG) targets the thyroid receptor. This antibody is known as the thyroid-stimulating antibody (TSI). In addition to TSI, antibodies against thyroid peroxidase and thyroglobulin are also found in Graves' disease.
• In this condition, the levels of free T4 increase while TSH decreases. This is due to TSI stimulating the TSH receptor on the thyroid, which drives the hyperthyroidism. In Graves' disease, the thyroid gland is symmetrically enlarged.
• Additional lab findings might include increased radioiodine uptake by the thyroid. The metabolic rate and heat production also increase, leading individuals to seek cooler environments. The cardiac output, contractility, and heart rate may also increase, potentially causing palpitations and arrhythmias due to increased B-adrenergic stimulation.

• There are many symptoms that can suggest a state of excess catecholamines, but circulating catecholamines are typically normal. These symptoms include weight loss despite increased food intake, protein wasting, muscle weakness, tremors, nervousness, and excessive sweating.
• A wide-eyed stare, known as exophthalmos, is common in patients with Graves' disease. It is caused by an infiltration of orbital soft tissues and extraocular muscles, leading to edema.
• Pretibial myxedema, a late manifestation of Graves' disease, refers to skin thickening and hardening on the lower legs. This autoimmune condition is caused by the production of thyrotropin receptor-stimulating antibodies. It appears as nonpitting edema that can sometimes look scaly, resembling an orange peel. It can spread from the tibia to the ankles and top of the foot. Pretibial myxedema should not be confused with myxedema coma, a severe hypothyroidism condition characterized by decreased mental status.
• Specific symptoms such as pretibial myxedema, exophthalmos, periorbital edema, and eye-movement limitations are only observed in hyperthyroidism due to Graves' disease. These symptoms are not caused by increased thyroid hormone levels, but by the autoimmune response directed against the TSH receptor. This receptor is widely distributed throughout the body, especially on adipocytes and fibroblasts.
• In Graves' disease, patients experience lymphocytic infiltration of the orbital and pretibial connective tissue due to increased TSH receptor expression in these regions. Activated T-cell released cytokines boost fibroblast proliferation and secretion of glycosaminoglycans, causing mucinous edema and tissue expansion. Progressive infiltration eventually leads to the development of Graves' ophthalmopathy and pretibial myxedema.
• If left untreated, hyperthyroidism can deteriorate into a condition known as "thyroid storm."