Fig. 20.8 Pathogenesis of Hashimoto thyroiditis. Breakdown of immune tolerance to thyroid autoantigens results in progressive autoimmune destruction of thyrocytes by infiltrating cytotoxic T cells, locally released cytokines, or antibody-dependent cytotoxicity.
Fig. 20.9 ). The thyroid follicles are atrophic and are lined in many areas by epithelial cells distinguished by the presence of abundant eosinophilic, granular cytoplasm, termed Hürthle, or oxyphil, cells. This is a metaplastic response of the normal low cuboidal follicular epithelium to ongoing injury; on ultrastructural examination, the Hürthle cells are characterized by numerous prominent mitochondria. Interstitial connective tissue is increased and may be abundant. Less commonly, the thyroid is small and atrophic as a result of more extensive fibrosis (fibrosing variant).
Hashimoto thyroiditis comes to clinical attention as painless enlargement of the thyroid, usually associated with some degree of hypothyroidism, often in a middle-age woman.
Fig. 20.9 Hashimoto thyroiditis. The thyroid parenchyma contains a dense lymphocytic infiltrate with germinal centers. Residual thyroid follicles lined by deeply eosinophilic Hürthle cells also are seen.
The enlargement of the gland usually is symmetric and diffuse, but in some cases it may be sufficiently localized to raise suspicion for neoplasm. In the usual clinical course, hypothyroidism develops gradually. In some cases, however, it may be preceded by transient thyrotoxicosis caused by disruption of thyroid follicles, with secondary release of thyroid hormones (hashitoxicosis). During this phase, free T4 and T3 concentrations are elevated, TSH is diminished, and radioactive iodine uptake is decreased. As hypothyroidism supervenes, T4 and T3 levels progressively fall, accompanied by a compensatory increase in TSH. Patients with Hashimoto thyroiditis often have other autoimmune diseases and are at increased risk for the development of B-cell non-Hodgkin lymphomas (Chapter 12), which typically arise within the thyroid gland. The relationship between Hashimoto disease and thyroid epithelial cancers remains controversial, with some morphologic and molecular studies suggesting a predisposition to papillary  carcinomas.
Subacute granulomatous thyroiditis, also known as de Quervain thyroiditis, is much less common than Hashimoto disease. De Quervain thyroiditis is most common between 30 and 50 years of age and, like other forms of thyroiditis, occurs more frequently in women than in men. Subacute thyroiditis is believed to be caused by a viral infection or an inflammatory process triggered by viral infections, and not by an autoimmune process. A majority of patients have a history of an upper-respiratory infection shortly before the onset of thyroiditis. Unlike in autoimmune thyroid disease, the immune response in subacute granulomatous thyroiditis is not self-perpetuating, so the process spontaneously remits.