ESPE Abstracts

NCCAH is considered the most common autosomal recessive endocrine disorder, with a carrier frequency of 1: 7 to 1: 25. The disorder is caused by mild mutations in the CYP21A2 gene retaining enzymatic activity of 20-50%. The genotype may be either mild/mild or mild/severe mutations. The partial enzymatic deficiency leads to increased production of adrenal androgens. The patients present with different degrees of postnatal virilization: precocious pubarche during childhood and polycystic ovary-like syndrome or infertility in adolescence and young adulthood. If untreated during childhood, they might have premature epiphyseal fusion and compromised adult height. We have shown that early hydrocortisone therapy initiated before the occurrence of significant bone age advancement improves adult height. We therefore recommend initiation of therapy at the first sign of androgen excess, with careful follow-up to avoid under and over-treatment. We also found that cases with the mild/severe genotype present earlier, and have more frequent central precocious puberty and more compromised adult height. These patients had significantly lower cortisol response to ACTH stimulation: 70% failed the short ACTH test, compared to 48% of the mild/mild genotype and 0% of the controls. We suggest that patients with the mild/severe genotype have a more severe phenotype and may need continuation of therapy and stress coverage during adulthood. As for fertility, we showed that the pregnancy and birth rates of women with NCCAH are similar to the general population and that glucocorticoid therapy does not affect pregnancy outcome, although it might shorten the time to conceive in a subgroup of patients who failed to conceive spontaneously. We also demonstrated that phenotypic variability is partially explained by the length of the CAG repeats within the androgen receptor, and that the addition of anti-androgen might therefore be beneficial for females with hirsutism.