Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia

Abstract

A B S T R A C T Patients with the "non-salt-losing" form of the adrenogenital syndrome were studied before and after suppression of adrenal cortical activity with carbohydrate-active steroids. The response of aldosterone secretion to sodium deprivation was measured; in some patients response to adrenocorticotropic hormone (ACTH) was measured as well.The aldosterone secretion was normal and responded normally to sodium deprivation in all patients studied during suppression with carbohydrate-active steroids. This finding suggests that 21-hydroxylation of progesterone is normal in this syndrome.The sole abnormality in the production of aldosterone in these patients was found to be excessive secretion of aldosterone while they were not receiving suppressive doses of carbohydrate-active steroids. This finding strongly supports the view that the biogenetic pathways through which aldosterone is produced from progesterone are intact in this syndrome.No patient showed hypertension or hypokalemic alkalosis despite very high aldosterone secretion rates. This observation suggests that the hyperaldosteronism is secondary to a tendency to sodium loss in the patient whose ACTH production is not suppressed.

Exchangeable Sodium and Aldosterone Secretion in Children with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

“…The ASR values of our six children can be regarded as on the high side. Above normal values for ASR in nonsalt losers have also been found in two of three cases by JAILER et al [23], and high values have also been reported by Ko-WARSKI et al [25] and by BARTTER et al [3].…”

“…They showed a response to ACTH with an increase in cortisol secretion, but this response was invariably less than normal. 24 Na excreted in the urine in 24 h. 3 Interval between cessation of treatment and the start of the investigation.…”

“…I) Steroid therapy brings a fall in the aldosterone secretion rate (3,21,25, and caw nos.3 and 6). 2) A positive relation between the excretion of pregnanetriol in urine and that of aldosterone has been described by HALL and HOKFELT [22] and by MATTOX et al 1281 in both types of CAH.…”

“…1-6) the ASR response to a low salt regime was certainly not greater than normal (yet the pool of Na, was reasonably well maintained). It is, therefore, difficult to understand why some cases show only a normal or subnormal rise in ASR with a low salt intake while others [3] show a very striking rise (to 3,244 pg/24 h).…”

Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor

“…In patients with the simple virilizing, non-salt-loosing form, 17a-OH-P concentration reaches 70 -240 nmol/l and in patients with the salt-loosing form 400 -1000 nmol/l (32,50). Regarding these high concentrations of 17a-OH-P, the anti-MC potency of 17a-OH-P, shown in this study, and the known antagonist effect of progesterone, give an explanation for the compensatory hyperaldosteronism in patients with the simple virilizing form (28,51). The salt wasting is probably due to the complete lack of 21-hydroxylase activity and of aldosterone and cortisol production.…”