Aldosterone Secretion Rate in Congenital Adrenal Hyperplasia. a Discussion of the Theories on the Pathogenesis of the Salt-losing Form of the Syndrome.

The most common form of the congenital adrenal hyperplasia syndrome is caused by an inefficient enzymatic hydroxylation of the adrenal steroids at the 21 position (1-4). The symptoms of this disease can be explained by a deficiency in cortisol secretion resulting in an increased ACTH output and an overproduction of androgens and cortisol precursors by the hyperplastic adrenals (5, 6). About a third of these patients manifest a marked tendency to sodium loss and potassium retention (7). The pathogenesis of this phenomenon has not yet been fully understood, and three major hypotheses have been advanced. The first was suggested by Crigler, Silverman, and Wilkins (8), who observed an increase in sodium diuresis in patients treated with ACTH (1, 9), as well as a decreasing requirement for desoxy-corticosterone acetate (DOCA) when they were treated with cortisone or corticosterone (8). These authors interpreted their results as suggesting the secretion of sodium-losing hormones by the patients' adrenals. Earlier, Darrow (10) had noted that patients with congenital adrenal hyperplasia and salt loss required amounts of DOCA or salt, or both, which were larger than those needed by Addisonian patients. Barnett and * McNamara (11) showed that the electrolyte disturbance in adrenal hyperplasia was different from that observed in patients with Addison's disease. All these findings were interpreted as suggesting the secretion of a salt-losing hormone or of a pattern of steroids conducive to salt loss in congenital adrenal hyperplasia. Several attempts to identify a sodium-losing factor in the patients' urine have failed (12-14). Another explanation was advanced by Bongio-vanni and Eberlein who pointed out that both the salt-losing and the nonsalt-losing forms of congenital adrenal hyperplasia are caused by the same hy-droxylation defect in the adrenal glands, the salt-losing form having an almost complete deficiency (15). They suggest that "a minimal amount of hydrocortisone is required for aldosterone to exert its metabolic action in man" (16). The untreated salt-losing patients would produce no cortisol or related corticoids, and therefore, aldosterone could be produced normally but its action would not be manifested. The total lack of cortisol secretion would also explain the need of large amounts of DOCA for the treatment of these patients. Blizzard, Liddle, Migeon, and Wilkins (17) studied aldosterone excretion in patients with congenital adrenal hyperplasia. They found low to normal aldosterone excretion in salt-losing patients with no increase on salt deprivation. Most of the patients with the nonsalt-losing form had an …