The following is a summary of “Genotype-Specific Cortisol Reserve in a Cohort of Subjects With Nonclassic Congenital Adrenal Hyperplasia (NCCAH),” published in the March 2024 issue of Endocrinology by Koren, et al.
Recent guidelines recommend discontinuing glucocorticoid therapy in patients with nonclassic congenital adrenal hyperplasia (NCCAH) upon reaching adult height. However, these guidelines do not distinguish between NCCAH genotype groups. For a study, researchers sought to compare ACTH-stimulated cortisol and 17-hydroxyprogesterone (17OHP) levels, and the prevalence of partial cortisol insufficiency in subjects with NCCAH carrying one mild and one severe (mild/severe) mutation versus subjects with biallelic mild (mild/mild) mutations.
They conducted a retrospective analysis of medical records from 122 patients presenting with postnatal virilization and diagnosed with NCCAH. Patients underwent standard intravenous 0.25 mg/m2 ACTH stimulation testing. Those with stimulated 17OHP levels ≥40 nmol/L were screened for the 9 most frequent CYP21A2 gene mutations, followed by multiplex ligation-dependent probe amplification. Partial cortisol deficiency was a stimulated cortisol level below 500 nmol/L.
Patients were divided into three genotype groups: 77 had the mild/mild genotype, mainly homozygous for the p.V281L mutation; 29 were compound heterozygous for mild/severe mutation, mainly p.V281L/p.I2Splice; and 16 were heterozygous for p.V281L and excluded from statistical analysis. Stimulated cortisol levels were significantly lower in the mild/severe group compared to the mild/mild group (mean ± SD, 480 ± 90 vs. 570 ± 125 nmol/L, P < .001). The mild/severe group showed a significantly higher rate of partial cortisol insufficiency (21/28, 75% vs. 28/71, 39%, P = .004). Peak 17OHP was significantly higher in the mild/severe group (198 ± 92 vs. 118 ± 50 nmol/L, P < .001).
The elevated prevalence of partial adrenal insufficiency in the mild/severe group highlighted the importance of carefully considering glucocorticoid therapy cessation and ensuring stress coverage in the population.
Reference: academic.oup.com/jcem/article-abstract/109/3/852/727565