Endocrine Abstracts

CAH results from an enzymatic defect in the synthesis of cortisol from cholesterol in the adrenal cortex. It is a monogenic disorder transmitted as an autosomal recessive trait. More than 90% of the cases are caused by a deficiency of 21-hydroxylase (21OHD). Patients with 21OHD are categorized into 2 main forms: classical (salt wasting and simple virilizing) and nonclassical (NC).

The frequency of the NC form varies in the different populations and the method of detection (hormonal, molecular) ranging from 1:100 to 1:1000. The NC form of CAH is looked for in subjects with premature adrenarche, increased acne, hirsutism, menstrual disorders, fertility problems or abortions, adrenal or testicular adenomas. A number of cases are completely asymptomatic, especially men, and are discovered either when investigating the family members of an index case or by serendipity.

Concerning genotyping, three point mutations have specifically been associated with NC CAH: V281L, P30L and P453S. In compound heterozygotes, the phenotype is determined by the least deleterious mutations. The overall data indicate that NC genotypes do not always predict phenotype. Thus in certain cases mild, unexpected virilization may be detected.

The management of patients with NC CAH includes genetic counseling especially in prospective or current pregnancy and the administration of glucocorticoids in symptomatic subjects. In asymptomatic patients incidentally diagnosed, there is a real dilemma since the patient has no clinical problem but there is a potential risk for adrenal or testicular adenoma or polycystic ovarian disease. In such cases a consensus document does not recommend treatment. One may suggest that if follow-up can be ensured the patient may remain without therapy. It must be emphasized however that there is not as yet evidence-based recommendation for the management of such cases and individualization is required.