primary hyperthyroidism

DEFINITION: Thyroid gland autonomously (or via stimulating antibodies) overproduces T3/T4. Negative feedback suppresses TSH. Distinguish from secondary (pituitary TSH-secreting adenoma: HIGH TSH, high T4) and from thyrotoxicosis without hyperthyroidism (e.g., thyroiditis, exogenous hormone, struma ovarii), where hormone is released or supplied rather than newly synthesized.

LABS: Low TSH, high free T4 and/or T3. Subclinical = low TSH with normal T4/T3. Radioactive iodine uptake (RAIU) is increased in primary hyperthyroidism: diffuse in Graves, patchy/focal in toxic MNG, single hot nodule in toxic adenoma. RAIU is LOW in thyroiditis, factitious thyrotoxicosis, and struma ovarii (ectopic tissue; neck uptake low).

CAUSES: - Graves disease (most common; ~60-80%): Type II hypersensitivity; IgG thyroid-stimulating immunoglobulins bind TSH receptor. Associated with HLA-DR3, women 20-50. Unique findings: diffuse goiter, exophthalmos/ophthalmopathy (fibroblast and orbital muscle glycosaminoglycan deposition), pretibial myxedema, thyroid acropachy. Histology: tall columnar follicular cells with scalloped colloid. - Toxic multinodular goiter: autonomous nodules, older patients, often iodine-deficient areas; can worsen after iodine load (Jod-Basedow phenomenon). - Toxic adenoma (Plummer): single autonomous nodule, often TSH receptor or Gs (GNAS) activating mutations; suppresses the rest of the gland. - Others: iodine-induced (amiodarone type 1), hCG-mediated (hyperemesis, molar pregnancy, choriocarcinoma, given hCG's TSH-like α subunit), struma ovarii (technically extrathyroidal).

CLINICAL FEATURES: Heat intolerance, weight loss with increased appetite, sweating, warm moist skin, tremor, anxiety, insomnia, palpitations/sinus tachycardia, atrial fibrillation (especially elderly), widened pulse pressure, hyperreflexia with proximal muscle weakness, diarrhea/hypermotility, oligomenorrhea, gynecomastia, osteoporosis (increased bone turnover), lid lag/stare. Mechanism: increased β-adrenergic receptor expression and increased Na/K-ATPase and basal metabolic rate.

COMPLICATIONS: Thyroid storm (precipitated by surgery, infection, trauma, iodine, or childbirth: fever, tachycardia, AMS, GI symptoms; Burch-Wartofsky score). Atrial fibrillation, heart failure, osteoporosis.

TREATMENT: - Symptomatic: β-blockers (propranolol also inhibits peripheral T4→T3 conversion). - Thionamides: methimazole (first-line, except first trimester pregnancy) and propylthiouracil (PTU; preferred in first trimester and thyroid storm because it also blocks peripheral deiodination). Both inhibit thyroid peroxidase (organification and coupling). Adverse effects: agranulocytosis (check WBC with fever/sore throat), aplastic anemia, hepatotoxicity (PTU, boxed warning), methimazole teratogenicity (aplasia cutis, choanal atresia). - Radioactive iodine ablation (definitive; contraindicated in pregnancy; can worsen Graves ophthalmopathy, so give steroids if present; leads to hypothyroidism needing levothyroxine). - Thyroidectomy: for large goiter, compressive symptoms, suspicion of malignancy, or ophthalmopathy. Complications: hypoparathyroidism (hypocalcemia), recurrent laryngeal nerve injury (hoarseness), hematoma. - Thyroid storm: β-blocker, PTU, then iodine (Wolff-Chaikoff effect, given ≥1 h after thionamide), glucocorticoids, supportive care.

PEARLS: Neonatal Graves can occur from transplacental TSI. Low TSH + high T4 = primary; high TSH + high T4 = secondary (TSH-oma) or thyroid hormone resistance. Euthyroid sick and thyroiditis (subacute de Quervain: painful, ↑ESR, low RAIU; Hashitoxicosis early phase) are common distractors.