1) Determining the prevalence of NCAH in unselected hyperandrogenic women in the Northeast (at the Johns Hopkins Hospital) and Southeast (at the University of Alabama at Birmingham) United States, and Puerto Rico (at the University of Puerto Rico). These studies indicated that the prevalence of NCAH in hyperandrogenic women in the United States is approximately 2%, although it may be lower in the African-American population.

2) Using prospective studies, the technique of screening for the disorder among hyperandrogenic women with the use of a basal 17-hydroxyprogesterone measurement, was studied. Essentially, a cut-off value of approximately 2 ng/ml for a basal 17-HP level obtained in the follicular phase of the menstrual cycle has a positive predictive value for NCAH of 16%; hormone levels below this cut-off value essentially exclude affected patients.

3) The early genetics of the disorder of NCAH were studied, and a unique mutation (PRO-453 to Ser) was first reported.

4) The risk of clinically-evident hyperandrogenism in carriers (heterozygotes) for congenital 21-hydroxylase deficiency was also assessed and was found to be relatively minimal.

5) The mechanisms underlying the excess androgen production in NCAH, in spite of relatively normal circulating ACTH levels, were studied and indicated that the androgen excess was primarily due to intrinsic defects in enzyme kinetics and to associated ovarian hyperandrogenism.

6) The clinical presentation of NCAH was studied in a large multi-center study and it was found that, contrary to earlier reports, the hyperandrogenic symptoms of the disorder appear to be progressive over time.

7) Other studies also indicted that there appears to be a loose association between the severity of the phenotype (appearance of the disorder) and the severity of the genotype (type of genetic abnormality).

Dr. Azziz has also coordinated a large multi-center collaborative group for the study of NCAH. The NCAH multi-center international study group includes investigators from the following sites: