Active and inactive renin in primary and secondary adrenal insufficiency and during ACTH infusion.

Abstract

Abstract. Prolonged low-dose ACTH infusion leads to a transient stimulation of plasma renin activity (PRA) and angiotensin II. In part 1 of the present study (infusion of 10 IU of ACTH per day for 38 h into 6 normal young males), it was shown that the concentration of active renin (aPRC) increases in parallel to PRA. Thus, the rise in PRA is either due to net active renin secretion by the kidney or to increased conversion of inactive into active renin. Since the plasma concentration of inactive renin (iPRC) tended to rise rather than to fall during ACTH infusion, peripheral activation of inactive renin is probably not the cause of the rise in aPRC. Part 2 of the study consisted in the measurement of plasma ACTH, cortisol, PRA, aPRC and iPRC in 10 patients (group I) with primary adrenocortical insufficiency (8 Addisonians, 2 adrenalectomized Cushing's) and in 9 patients with hypopituitarism (group II) after short-term withdrawal of hydrocortisone substition therapy. ACTH was 1770 ± 390 pg/ml in the former and 20 ± 4 pg/ml in the latter group. PRA and aPRC were higher and the ratio iPRC:aPRC lower in group I than in group II. This might indicate stimulation of active renin formation by ACTH. However, it is unlikely that the higher aPRC levels in group I are due to increased peripheral activation of inactive renin, since the relationship between aPRC and the ratio iPRC:aPRC fell on the same curve in both groups. ACTH or an ACTH-dependent mechanism raises aPRC, probably by stimulating its renal secretion rather than by peripheral activation of inactive renin.