In vitro responses of aldosterone-producing adenomas to angiotensin II and ACTH after treatment with spironolactone before adrenalectomy

Aldosterone-producing adenomas in patients who have not been given spironolactone are more responsive to ACTH than to angiotensin II. In vitro, adenomas respond to ACTH, but their response to angiotensin II has not been clearly defined. Treatment with spironolactone has been given before the removal of some of the adenomas studied in vitro, and it can blunt increases in plasma aldosterone concentrations that occur in response to increases in renin activity. To assess the effect of preoperative spironolactone therapy on the responsiveness of aldosterone-producing adenomas in vitro, tissue from five patients with adenomas was incubated for 4 hours with and without angiotensin II and ACTH, 10(-7) to 10(-5) mol/L. The responsiveness of the adenomas was then related to the duration of preoperative spironolactone therapy. The serum potassium concentration was normal in the patients before the operations. Adenoma tissue from a patient given spironolactone for 4 days was responsive to angiotensin II and to ACTH. Treatment of longer duration with spironolactone appeared to be associated with a pattern of decreasing responsiveness to ACTH and an absence of response to angiotensin II in vitro. Aldosterone production by nonadenomatous adrenal tissue did not respond to angiotensin II or to ACTH. Our results suggest that preoperative spironolactone therapy might decrease the responsiveness of aldosterone-producing adenomas to angiotensin II and ACTH in vitro. Therefore, studies of aldosterone-producing adenomas in vitro should consider the possible effects of preoperative treatment with spironolactone on the responsiveness of the adenomas to angiotensin II and ACTH.