Studies of impaired aldosterone response to spironolactone-induced renin and potassium elevations in adenomatous but not hyperplastic primary aldosteronism.
Spironolactone (SPL) corrects hypertension, hypokalemia, and hyporeninemia in patients with primary hyperaldosteronism (PHA) by blocking mineralocorticoid (MCH) receptors. We evaluated the effect of continuous SPL treatment (100 to 300 mg/day for 7 days to 9 years) on plasma renin (PRC), potassium, aldosterone (PA), 18-hydroxycorticosterone (18-OHB), deoxycorticosterone (DOC), and corticosterone (B) concentrations and 24-hour urinary excretion of aldosterone (UA) in 24 patients with PHA (15 with an aldosterone-producing adenoma [APA] and nine with idiopathic PHA [IHA]). Despite the normalization of PRC and K in both APA and IHA patients by SPL, UA and PA failed to increase in APA (55.8 +/- 8.8 to 51.4 +/- 7.3 micrograms/24 hr and 54.0 +/- 9.4 to 44.6 +/- 6.2 ng/dl, respectively) in contrast to rises in IHA patients (22.3 +/- 2.5 to 69.3 +/- 10.3 micrograms/24 hr and 16.0 +/- 1.0 to 49.9 +/- 9.9 ng/dl). Similar corrections with amiloride (20-40 mg/day for 2 months) in one patient with APA produced a three- to fourfold increase in UA and PA. In addition, while on SPL the characteristic fall or no change in PA and 18-OHB during upright posture persisted in all APA patients despite further increases in PRC (4.48 +/- 1.15 to 7.86 +/- 1.89) and K (4.0 +/- 0.1 to 4.3 +/- 0.1). The patterns of the aldosterone precursors, DOC, B, and 18-OHB, and their ratios to acute stimulation with cosyntropin were not altered by SPL. Thus, SPL treatment causes a sustained impairment of the aldosterone secretory response to normalized PRC and K, but not to ACTH stimulation, only in patients with APA.
D000236:Adenoma / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000311:Adrenal Glands / Q000473:pathology; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D003366:Cosyntropin; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000188:drug therapy*; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D011187:Posture; D011188:Potassium / Q000097:blood*; D012083:Renin / Q000097:blood*; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D003366:Cosyntropin; D013148:Spironolactone; D000450:Aldosterone; D012083:Renin; D011188:Potassium