Aldosterone-to-Renin Ratio as a Marker for Disease Severity in 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia

Abstract

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21 OHD) is classified clinically in decreasing order of severity into salt-wasting, simple-virilizing, and nonclassical forms. Causative mutations in the CYP21A2 gene dictate the degrees of adrenal enzyme defect. Salt-wasting crises due to aldosterone deficiency are clinically apparent in the salt-wasting form but not in other forms of 21 OHD. This study examined the ratio of serum aldosterone to plasma renin activity as an index of sodium wasting in patients with 21 OHD CAH, heterozygotes, and normal individuals. This was a cross-sectional, retrospective, noninterventional study. A total of 402 individuals were included: 224 patients affected with 21 OHD CAH and 178 unaffected subjects. Classification into each diagnostic group was made primarily on the basis of clinical and hormonal features. Affected or unaffected status was confirmed by genotype of CYP21A2. All subjects were on ad lib diets without restrictions. Salt-wasting status was examined by sodium deprivation testing in 32 salt-wasting subjects and 14 simple virilizing subjects. The ratio of serum aldosterone to plasma renin activity was found to discriminate well between the different groups of disease severity. The lowest ratios, indicative of the least sodium conservation, were seen in the salt-wasting group with increasing ratios in the simple virilizing, nonclassical, and unaffected groups. This ratio remained stable with age. The ratio of serum aldosterone to plasma renin activity provides a simple index to compare groups of patients with varying degrees of 21 OHD.