A 28-year-old man with an adrenal incidentaloma undergoes overnight 1 mg dexamethasone suppression test. Post-dexamethasone morning cortisol is 8 µg/dL (normal < 1.8 µg/dL). Which zone of the adrenal cortex and which enzyme pathway is most likely dysfunctional or autonomous?
- A Zona glomerulosa; aldosterone excess via CYP11B2 bypassing renin-angiotensin system
- B Zona reticularis; DHEA excess feeding back to suppress ACTH insufficiently
- C Zona fasciculata; autonomous cortisol production via CYP11B1 (11β-hydroxylase) independent of ACTH ✓
- D Adrenal medulla; catecholamine excess cross-reacting with cortisol immunoassay
Correct answer: C. Zona fasciculata; autonomous cortisol production via CYP11B1 (11β-hydroxylase) independent of ACTH
Explanation
Autonomous cortisol-secreting adrenal adenomas arise from the zona fasciculata and constitutively activate the cholesterol → cortisol pathway, with CYP11B1 (11β-hydroxylase) being the final enzymatic step converting 11-deoxycortisol to cortisol. Because cortisol secretion is ACTH-independent, exogenous glucocorticoid (dexamethasone) cannot suppress it via the pituitary feedback axis, resulting in a non-suppressible cortisol—the diagnostic hallmark of primary adrenal Cushing syndrome.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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