Renin and renin substrate in primary adrenal insufficiency: Contrasting effects of glucocorticoid and mineralocorticoid deficiency

Abstract

Overactivity of the renin-angiotensin system has recently been shown to be important in circulatory homeostasis in adrenocortical failure. However, renin substrate levels decrease in experimentally induced glucocorticoid deficiency, and this can impair both the function of the renin-angiotensin system and its accurate assessment by measurement of renin activity. In order to define the effects of spontaneous steroid deficiency, renin concentration activity and renin substrate were assessed before and after treatment in seven patients with Addison's disease who showed varying degrees of aldosterone and cortisol deficiency. Severe adrenocortical failure, affecting both aldosterone and cortisol, resulted in a gross increase in renin concentration with substrate levels reduced to less than 10 per cent of the mean normal level. Renin excess was poorly reflected by measurement of renin activity when substrate depletion was severe. Substrate deficiency was closely related to the degree of cortisol lack, i.e., renin substrate showed a positive correlation with the level of plasma cortisol before treatment (r = 0.94, p < 0.005). In severe glucocorticoid deficiency, with preservation of normal aldosterone secretion, substrate was very low without renin excess, indicating that severe substrate depletion can occur without increased utilization. With marked renin excess in predominant mineralocorticoid deficiency and in untreated diabetic ketoacidosis, substrate remained normal, indicating that renin excess per se does not lead to substrate depletion. These findings indicate that although mineralocorticoid failure stimulates renin release, adequate glucocorticoid production is crucial in preventing substrate depletion. The homeostatic role of the renin-angiotensin system may be impaired in severe adrenal failure despite an appropriate renin response to mineralocorticoid deficiency. Depletion of substrate may be a factor which contributes to circulatory failure in glucocorticoid deficiency.