Effects of fludrocortisone withdrawal on plasma angiotensin II, ACTH, vasopressin, and potassium in patients with Addison's disease.
We attempted to answer to the question whether excessive rises in endogenous plasma angiotensin II (AII) stimulate ACTH secretion by measuring PRA, AII, AVP, ACTH, and cortisol in 8 patients with Addison's disease before and after withdrawal of fludrocortisone substitution. Blood was drawn at 14.30 h, exactly 6 1/2 h after the morning dose of hydrocortisone had been taken. PRA and AII were initially higher than normal in 4 patients. After withdrawal of fludrocortisone for 1 or 2 weeks, PRA and AII rose markedly in 4 patients (up to 260 ng/l) without concomitant changes in plasma ACTH levels (r = -0.081, AII vs ACTH). Changes in plasma cortisol could not have obscured a stimulatory effect of AII on ACTH by variable feedback inhibition of ACTH release. The increase in plasma AII levels in the 4 patients was larger than that observed in a previous study in normal subjects after rigorous dietary sodium restriction. In all patients, hyperkalaemia developed after fludrocortisone withdrawal, independent of changes in PRA and AII. Rises in PRA, AII, and plasma potassium were partially reversed by increased sodium intake and further suppressed by resumption of fludrocortisone therapy. Plasma AVP remained in the normal range after fludrocortisone withdrawal, but was slightly elevated after increasing salt intake without fludrocortisone administration.


CONCLUSIONS
Rises of endogenous plasma AII to levels tenfold higher than normal do not stimulate ACTH release. AII is probably not a physiological modulator of ACTH secretion. Mineralocorticoid substitution in Addison's disease should be monitored by plasma potassium measurement. Hyperkalaemia may coexist with normal PRA.(ABSTRACT TRUNCATED AT 250 WORDS)
D000224:Addison Disease / Q000097:blood / Q000188:drug therapy*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000804:Angiotensin II / Q000097:blood*; D001127:Arginine Vasopressin / Q000097:blood*; D005260:Female; D005438:Fludrocortisone / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood*; D012083:Renin / Q000097:blood
D000804:Angiotensin II; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D012083:Renin; D011188:Potassium; D005438:Fludrocortisone