autoimmune thyroiditis

**Definition/Types:** Autoimmune thyroiditis is a group of disorders in which the immune system attacks the thyroid. Types: (1) Hashimoto (chronic lymphocytic) thyroiditis, the most common; (2) atrophic thyroiditis (fibrous variant, no goiter); (3) painless (silent/sporadic) thyroiditis, a variant with transient thyrotoxicosis; (4) postpartum thyroiditis, a painless thyroiditis within 12 months after delivery; (5) Graves disease, which is also autoimmune but stimulatory and is usually classified separately. IgG4-related (Riedel) thyroiditis is a related but distinct fibrosing entity.

**Pathophysiology (Hashimoto):** - Loss of self-tolerance leads to a CD4+ Th1 and CD8+ cytotoxic T-cell attack on thyroid follicular cells (type IV hypersensitivity), with a contribution from antibody-dependent cell-mediated cytotoxicity (type II). - Autoantibodies: anti-thyroid peroxidase (anti-TPO, most sensitive and specific) and anti-thyroglobulin (anti-Tg). - Genetics: HLA-DR3, DR5, CTLA-4, and PTPN22 variants. Higher risk in women and in Turner and Down syndromes. - Associated with other autoimmune diseases (T1DM, pernicious anemia, Addison disease, vitiligo, celiac disease, SLE, RA), including autoimmune polyglandular syndrome type 2. - Environmental factors: high iodine intake and selenium deficiency.

**Clinical features:** - Typically a middle-aged woman (30–50 years) with a painless, diffusely enlarged, firm, rubbery goiter. - Course: an early transient "Hashitoxicosis" phase (follicle destruction releases preformed hormone), then euthyroid, then hypothyroidism. - Hypothyroid symptoms: fatigue, cold intolerance, weight gain, constipation, dry skin, bradycardia, delayed relaxation of reflexes, myxedema, and menstrual irregularities (menorrhagia). - In children, it can cause growth failure and delayed puberty.

**Diagnosis:** - Labs: elevated TSH with low free T4 (overt hypothyroidism); elevated TSH with normal free T4 (subclinical hypothyroidism). Positive anti-TPO and/or anti-Tg. - Histology: lymphocytic and plasma cell infiltrate with germinal centers, Hürthle (oncocytic) cells with eosinophilic cytoplasm, and follicular atrophy and fibrosis. - Radioiodine uptake is low or patchy. Ultrasound shows a heterogeneous, hypoechoic gland.

**Treatment:** - Levothyroxine (T4), titrated to a normal TSH. - Treat during pregnancy, with a higher dose requirement. - Treat subclinical hypothyroidism if TSH is markedly elevated, anti-TPO is positive, the patient is symptomatic or pregnant, or there is infertility.

**Complications:** - Primary thyroid lymphoma, mainly marginal zone B-cell/MALT lymphoma. Suspect it with rapid enlargement of a long-standing goiter. - Myxedema coma in severe untreated disease. - Congenital hypothyroidism risk if a pregnant patient is untreated, because maternal antibodies cross the placenta.

**Board pearls and differentials:** - Hashimoto: painless, firm goiter, anti-TPO+, Hürthle cells, germinal centers. - Subacute (de Quervain) granulomatous thyroiditis: painful, post-viral, elevated ESR, granulomas with multinucleated giant cells, self-limited. - Riedel thyroiditis: rock-hard, fixed "woody" fibrosis extending into neck structures, IgG4-related. - Graves disease: TSH-receptor stimulating Ig (type II hypersensitivity), diffuse goiter, ophthalmopathy, pretibial myxedema, high radioiodine uptake. - Postpartum thyroiditis: painless, with a thyrotoxic phase followed by a hypothyroid phase, and often anti-TPO+. It may recur in later pregnancies. - Beta-blockers treat the thyrotoxic phase. Antithyroid drugs are not used, because the thyrotoxicosis comes from release of stored hormone, not increased synthesis.