ESPE Abstracts

Background: Recent guidelines suggest that NCCAH subjects stop their glucocorticoid therapy after achieving adult height. However, these guidelines do not differentiate between genotype groups within the NCCAH population.

Aim: Compare ACTH stimulated cortisol and 17-hydroxyprogesterone (17OHP) levels, and the rate of partial cortisol insufficiency in NCCAH subjects carrying one mild and one severe (mild/severe) mutation vs. subjects with bi-allelic mild (mild/mild) mutations.

Methods: A retrospective evaluation of the medical records of 122 patients who presented with postnatal virilization and were diagnosed with NCCAH. Patients with postnatal virilization (mainly precocious adrenarche) underwent the standard intravenous 0.25 mg/m2 ACTH stimulation test. Those with stimulated 17OHP level above 40 nmol/L were screened for the nine most frequent CYP21A2 gene mutations followed by Multiplex Ligation-dependent Probe Amplification (MLPA). A stimulated cortisol level below 500 nmol/L was defined as partial cortisol defficiency.

Results: The NCCAH patients (n=122) were subdivided according to their genotype into three groups: 77 carried the mild/mild genotype, mainly homozygous for pV281L mutation; 29 were compound heterozygous for one mild and one severe mutation, mainly p.V281L/ p. I2Splice and 16 were heterozygous for p.V281L, and therefore were excluded from the statistical evaluation. Stimulated cortisol levels were significantly lower in the mild/severe than in the mild/mild group (mean±sd, 480± 90 vs 570 ±125 nmol/L, P<0.001). The mild/severe group exhibited a significantly higher rate of partial cortisol insufficiency (21/28, 75% vs 28/71, 39%, P= 0.004). Peak 17OHP was significantly higher in the mild/severe group (198± 92 vs 118 ± 50 nmol/L, P<0.001). A cutoff 17OHP level of 170 nmol/L is suggested to differentiate between groups.

Conclusion: The high rate of partial adrenal insufficiency in the mild/severe group underscores the need to carefully consider the value of glucocorticoid therapy cessation and the importance of stress coverage in this group.