Primary adrenal cortical insufficiency (Addison disease) in a 30-year-old woman shows bilateral adrenal enlargement on CT and serum 21-hydroxylase antibodies. Autoimmune destruction of the adrenal cortex is predominantly mediated by:

• A Anti-21-hydroxylase IgG antibodies directly inhibiting enzyme activity
• B Immune complex deposition in adrenal sinusoids activating complement
• C Natural killer cell-mediated cytotoxicity without T-cell involvement
• D Cytotoxic CD8+ T cells and CD4+ Th1-driven macrophage-mediated destruction of zona fasciculata and reticularis ✓

Explanation

Autoimmune Addison disease is a T-cell-mediated (type IV hypersensitivity) destruction of the adrenal cortex. 21-hydroxylase (CYP21A2) is the primary autoantigen. Autoreactive CD8+ cytotoxic T lymphocytes and CD4+ Th1 cells directed against adrenocortical antigens drive the inflammatory destruction, progressively affecting all three zones but sparing the medulla. Anti-21-hydroxylase antibodies serve as a serological marker and may block enzyme activity, but the tissue destruction is primarily T-cell-mediated. The association with APS-1 (AIRE mutation) and APS-2 (CTLA4, PTPN22 polymorphisms) confirms T-regulatory cell dysfunction.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.