Genotyping Steroid 21-Hydroxylase Deficiency: Hormonal Reference Data*

TLDR

Hormonal reference nomograms of adrenal hormone levels enable genotyping of steroid 21‑hydroxylase deficiency in congenital adrenal hyperplasia. The authors use 360‑ and 60‑minute ACTH stimulation tests, assigning patients to genotype groups based on regression‑line hormone values, and demonstrate that the shorter 60‑minute test is equally reliable. The nomograms, based on 17‑hydroxyprogesterone and delta‑4‑androstenedione, accurately differentiate classical, nonclassical, and heterozygous 21‑hydroxylase deficiency cases, providing a powerful tool for genotype assignment.

Abstract

Hormonal reference data, in the form of nomograms relating baseline and stimulated levels of adrenal hormones, provide a means of genotyping steroid 21-hydroxylase (21-OH) deficiency in congenital adrenal hyperplasia. Data from both 360- and 60-min ACTH stimulation tests are given. The serum hormone concentrations that have proven most useful in classifying 21-OH deficiency are 17-hydroxyprogesterone and delta 4-androstenedione. These nomograms clearly distinguish the patient with classical 21-OH deficiency from those with the milder symptomatic and asymptomatic nonclassical forms of 21-OH deficiency (previously referred to as late onset and cryptic forms) as well as heterozygotes for all of the forms and those subjects predicted by HLA genotyping to be unaffected. The nomograms also can identify individuals heterozygous for 21-OH deficiency in the general population who have a characteristic heterozygote response. These nomograms provide a powerful tool by which to assign the 21-OH deficiency genotype. Patients whose hormonal values fall on the regression line within a defined group are assigned to that group. In view of the strong correlation between the 60- and 360-min ACTH stimulation tests, the less cumbersome and shorter 60-min test can be used with the same confidence as the longer test.