Histological and biochemical distinctiveness of atypical aldosterone-producing adenomas responsive to upright posture and angiotensin.

Fifteen patients with primary aldosteronism were classified as angiotensin II-unresponsive aldosterone-producing adenoma (AII-U APA, n = 9), or angiotensin II-responsive aldosterone-producing adenoma (AII-R APA, n = 6), based on the responsiveness of aldosterone to upright posture and to angiotensin II infusion. Lack of aldosterone response to angiotensin II infusion immediately postoperatively in the AII-R APA subtype was consistent with previous responsiveness residing solely within the adenoma. Cortisol levels in five of the six patients with AII-R APA failed to suppress normally with dexamethasone consistent with some autonomous production of cortisol by the adenoma. In contrast, cortisol levels suppressed normally during dexamethasone administration in all patients with AII-U APA. This biochemical distinction can be added to the previously described overproduction of 18-oxo cortisol in AII-U APA but not in AII-R APA. Histological examination of adenoma sections revealed predominantly (greater than or equal to 50%) zona fasciculata type cells in AII-U APA. In contrast, AII-R APA contained less than 20% zona fasciculata type. Thus, biochemical differences between AII-U APA and AII-R APA subtypes of primary aldosteronism may be due to underlying differences in cellular composition of the aldosterone-producing adenomas.