Snapshot A 27-year-old woman with vitiligo presents to her primary care physician with progressive fatigue and weight loss despite a good appetite. On exam, her blood pressure is 170/110 mmHg, pulse is 110/min, diaphoretic, displays brisk reflexes, and has bilateral exophthalmos. Introduction Clinical definition autoimmune hyperthyroidism Genetics HLA-DRB1 and HLA-DQB1 PTNP22 Associated conditions polyglandular autoimmune syndrome pernicious anemia vitiligo diabetes Epidemiology Demographics the most common cause of hyperthyroidism in the United States female dominant typically 20-40 years of age ETIOLOGY Pathogenesis triggered by stress e.g. childbirth, infection, steroid withdrawal, and trauma to the thyroid stimulating autoantibodies against the TSH receptor leading to the overproduction of thyroid hormone type II hypersensitivity pituitary TSH is suppressed via negative feedback from elevated thyroid hormone Presentation Symptoms tachycardia and/or palpitations thyroid hormone increases heart rate and contractility and decreases systemic vascular resistance fatigue and muscle weakness weight loss hyperactivity and/or tremulousness diarrhea warm moist skin and sweating heat intolerance eye pain and/or double vision Physical exam hypertension and/or arrhythmias enlargement ophthalmopathy (proptosis and exophthalmos) the hallmark of Graves disease but not always present often worsens after radioiodine ablation symmetrical, non-tender thyroid enlargement myxedema dermal accumulation of mucopolysaccharides non-pitting hyperreflexia imaging Radioactive iodine (123I) thyroid scan contraindicated in pregnancy defer to autoantibody assays Computed tomography (CT) scan or magnetic resonance image (MRI) of the orbits evaluation of ophthalmopathy Studies Diagnostic testing diagnostic approach screening for patients with clinical suspicion autoantibody titers are diagnostic imaging to differentiate etiologies of hyperthyroidism ancillary laboratory tests for associated dysregulation studies TSH level initial test of choice thyroid hormone level start with T4 level (total or free) if T4 level is normal, T3 level may be helpful autoantibody assays anti-TSH antibodies are almost always positive diagnostic for Graves complete blood count would demonstrate associated normocytic anemia, low-normal leukocytes, and low-normal platelets lipid profile would demonstrate associated low total cholesterol and triglyceride biopsy not routinely indicated but would show lymphocytic infiltrates and follicular hypertrophy Differential Multinodular toxic goiter distinguishing factors patchy uptake on 123I thyroid scan more common in elderly patients Toxic thyroid adenoma distinguishing factor single nodule with uptake on 123I thyroid scan Iatrogenic distinguishing factors excessive levothyroxine intake no increase in uptake on 123I thyroid scan DIAGNOSIS Diagnostic criteria ↓ TSH and ↑ T4 if T4 is normal, then possibly ↑ T3 positive anti-TSH antibodies radioactive iodine (123I) thyroid scan diffusely increased uptake differentiates Graves from other etiologies of hyperthyroidism Treatment Medical treatment first-line propranolol indication sympathetic symptoms such as palpitations, muscle weakness, and/or anxiety wean when thionamides take effect not definitive treatment indicated for atrial fibrillation secondary to hyperthyroidism (metoprolol) second-line thionamides methimazole and propylthiouracil mechanism inhibits thyroid hormone synthesis indication propylthiouracil during pregnancy adverse effects agranulocytosis discontinue and obtain CBC with differential if any signs of infection hepatotoxicity long-term remission in a minority of patients not definitive treatment third-line radioiodine ablation (131I) most common treatment definitive treatment mechanism destruction of thyroid follicular cells patients transition to hypothryoidism 3-6 months post-ablation, and subsequently require life-long thyroid replacement medication release of thyroid hormone secondary to destruction may lead to a transient worsening of symptoms pretreat with glucocorticoids indication failed antithyroid drugs contraindication pregnancy and breastfeeding Surgical treatment thyroidectomy indication cannot tolerate medical therapy pregnancy can be safely performed in the 2nd trimester allergy very large goiter Special considerations in pregnancy first line of treatment propranolol propylthiouracil with ophthalmopathy steroids surgical decompression orbital radiation Complications Thyroid storm can be life-threatening with fatal arrhythmia Pregnancy complications anti-TSH receptor antibodies may cross placenta and lead to fetal hyperthyroidism cretinism from contraindicated radioiodine ablation Thyroidectomy complications hypothyroidism laryngeal nerve palsy hypoparathyroidism and hypocalcemia ‘