ALDOSTERONE- AND CORTISOL SECRETION RATES IN INFANTS AND CHILDREN WITH CONGENITAL ADRENAL HYPERPLASIA SUGGESTING DIFFERENT 21-HYDROXYLATION DEFECTS IN »SALT-LOSERS« AND »NON SALT-LOSERS«

Abstract

ABSTRACT Aldosterone- and cortisol secretion rates were determined in nine infants and children with congenital adrenal hyperplasia (21-hydroxylation defects), three with the salt-losing type. Aldosterone secretion rates were determined before and after salt-deprivation for 4–6 days, using the double isotope dilution technique of Kliman & Peterson (1960). Cortisol secretion rates were determined before and on the third day of stimulation with ACTH-gel, 2 × 60 IU per day, using the method described by Cope & Black (1958). Aldosterone secretion rates were normal in the »non salt-losers« (60–125 μg/24 h) and rose after salt-deprivation (100–380 μg/24 h). Extremely low values were found in the three patients with the salt-losing type (< 10 μg/24 h) and during salt-deprivation no increase was observed. Cortisol secretion rates before ACTH were in the normal range for all patients (4.2–34 mg/24 h; 12–33 mg/m2/24 h) except for one infant with the salt-losing type (< 0.5 mg/24 h). ACTH raised cortisol secretion rates in all »non salt-losers« (17–104 mg/24 h), but the increase was less than could be expected under normal conditions and the relative defect in the biosynthesis of cortisol was demonstrated in this way. Cortisol secretion rates after ACTH in the »salt-losers« were distinctly lower as compared with the »non salt-losers«. »Salt-losing« and »non salt-losing« types of congenital adrenal hyperplasia as a result of 21-hydroxylation defects in the biosynthesis of cortisol and aldosterone represent two different genotypes. The results of these studies also suggest that both groups of patients represent biochemically two different types of the same disorder. This could be explained by two different genetically controlled changes in the 21-hydroxylation process, resulting in a different defect in the hydroxylation of progesterone and 17α-hydroxyprogesterone.