Aldosterone escape to chronic ACTH administration in man

Abstract

Abstract. Prolonged ACTH administration produces a transient and self-limiting stimulation of aldosterone secretion which has been attributed to sodium retention, to inhibition of final enzymatic steps of aldosterone biosynthesis and/or to a morphological change of the glomerulosa cells. This study was undertaken to determine the possible role of the renin-angiotensin system in mediating the aldosterone escape to repeated ACTH stimulation. We studied in normal male volunteers the effect of a 4 day ACTH administration on urinary aldosterone metabolite excretion (3 oxo-conjugate and tetrahydroaldosterone) during concomitant diuretic administration (spironolactone or triamterene). In addition the plasma aldosterone response to acute iv stimulation with ACTH before and during the corticotrophin-induced 'refractory state' was examined both on normal and on low sodium diet. Spironolactone was unable to counteract the sodium retention induced by ACTH stimulation; aldosterone excretion showed the same transient increase as with ACTH alone while plasma renin activity remained low. Triamterene produced a negative sodium balance, a significantly more sustained increase in aldosterone excretion and an increase in plasma renin activity. In either situation the two metabolites of aldosterone showed the same pattern of excretion. The plasma aldosterone response to acute iv ACTH stimulation was completely blocked during the corticotrophin-induced 'refractory state' on normal sodium intake, whereas on low sodium diet a clear-cut response was still obtained. These data suggest that the transient effect of ACTH on aldosterone secretion is dependent on the state of activity of the renin-angiotensin system. When renin was stimulated by low sodium intake or sodium depletion, the aldosterone response to repeated ACTH administration was more sustained, and when renin was stimulated by low sodium intake, the aldosterone response to acute ACTH was maintained. In conclusion we suggest that the renin-angiotensin system is able to delay but not to suppress the changes induced in the zona glomerulosa by prolonged ACTH stimulation.