Sodium Homeostasis and Aldosterone Secretion in Salt-Losing Congenital Adrenal Hyperplasia*

Abstract

Sodium balance studies were performed on fourteen subjects (ages 2-22 yr) with salt-losing congenital adrenal hyperplasia 21-hydroxylase deficiency. Glucocorticoid therapy was maintained, but mineralocorticoid therapy had been discontinued. All subjects showed evidence of a block in aldosterone biosynthesis, plasma aldosterone (PA), and aldosterone secretion rate (ASR) being low relative to plasma renin activity. Three subjects demonstrated severe sodium wasting with markedly decreased or unmeasurable PA and ASR. However, 11 had concentrations and/or ASR values which were appropriate or elevated relative to sodium intake. Four of the 11 maintained sodium homeostasis on a normal sodium intake. The remaining 7 showed evidence of sodium loss which was excessive for PA and/or ASR. Of these, 5 had incomplete suppression of the pituitary-adrenal axis as evidenced by elevated urinary 17-ketosteroids and pregnanetriol; the other 2 subjects had low values for these tests as well as plasma 17a-hydroxyprogesterone. In those subjects under adequate pituitary-adrenal suppression, sodium balance was achieved when PA was >10 ng/dl, whereas in the 5 subjects with incomplete suppression, sodium balance was achieved when PA was &50 ng/dl. Thus under the conditions normally encountered in treated congenital adrenal hyperplasia patients, there appeared to be a marked decrease in sensitivity to aldosterone with incomplete pituitary-adrenal suppression. This could be explained by ACTH-dependent steroidal mineralocorticoid antagonists. Two subjects showed evidence of mineralocorticoid resistance apparently unrelated to ACTH-dependent steroids. Furthermore, when the efficiency of sodium conservation was compared to ASR for all subjects under adequate pituitary-adrenal suppression, an imperfect correlation existed. These findings suggested the possibility that marked differences in sensitivity to aldosterone existed. Two possible mechanisms were suggested: 1) differences in intrinsic renal sensitivity to aldosterone, and 2) renin-dependent aldosterone antagonists. (J Clin Endocrinol Metab 48: 430, 1979)