Detection of heterozygote carriers of congenital adrenal hyperplasia

Heterozygote carriers of 21-hydroxylase deficiency (21-OHD) cannot be detected by measurements of basal adrenal secretion. Attempts were made to reveal the latent metabolic block by ACTH stimulation and determination of plasma 17-hydroxyprogesterone (17-OHP). Overlapping of the response curves between normals and carriers prevented their use for individual prediction purposes. The test sensitivity was improved as follows: endogenous ACTH interference was suppressed by dexamethasone prior to I.V. injection of ACTH: plasma 17-OHP, cortisol (F), progesterone (P), corticosterone (B) and androstenedione (AD) were measured (during the 1 h duration of the test): parameters analyzed were the ratio of plasma increments between precursors and end-products (Δ17-OHP/ΔF, ΔP/ΔB, Δ17-OHP/ΔAD) at corresponding times: data were analysed by a stepwise discriminant analysis. The test was performed in 22 normal adults and 14 parents of children with 21-OHD. The following results were obtained: significant alterations in the metabolic pathways of F and B but not in the conversion of 17-OHP to AD were demonstrated in carriers; addition of ΔP/ΔB results did not improve the discriminant potency of statistical analysis performed in the Δ17-OHP/ΔF data; within the limits imposed by the number of subjects studied, the discriminant analysis applied to the Δ17-OHP/ΔF data revealed a combination of variables which lead to a 91% correct classification for normals and carriers.SCOPUS: NotDefined.j