Thyroid Disorders: Hyperthyroidism and Autoimmune Thyroiditis

Hyperthyroidism results from excessive synthesis and secretion of thyroid hormones (T3 and T4). Graves disease, the most common cause, is an autoimmune disorder in which thyroid-stimulating immunoglobulins (TSI) bind and activate the TSH receptor, causing unregulated thyroid hormone production and diffuse gland enlargement. TSI-mediated stimulation of orbital fibroblasts and retroorbital fat/muscle expansion produces Graves ophthalmopathy. Toxic multinodular goiter results from autonomously functioning thyroid nodules with activating mutations in the TSH receptor or Gs-alpha subunit. Hashimoto thyroiditis is the most common cause of hypothyroidism in iodine-sufficient areas, mediated by CD4+ and CD8+ T lymphocytes and anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies that destroy thyroid follicular cells through antibody-dependent cell-mediated cytotoxicity and complement fixation. Subacute (de Quervain) thyroiditis follows viral infection, causing painful thyroid inflammation with transient thyrotoxicosis from preformed hormone release, followed by hypothyroidism, then recovery. Thyroid storm is a life-threatening thyrotoxic crisis with fever >104°F, tachycardia, delirium, and multiorgan dysfunction requiring emergent treatment with PTU (blocks synthesis and peripheral T4-to-T3 conversion), beta-blockers, iodine solution (given 1 hour after PTU), and corticosteroids.