Normally, the adrenal gland converts cholesterol to cortisone and other hormones through a series of enzyme mediated reactions that are regulated through feed-back loops. In some individuals, however, enzyme deficiencies can lead to a build-up of certain intermediate hormones along the pathway toward cortisol, a condition called congenital adrenal hyperplasia. The most common of these enzyme deficiencies, 21-hydroxylase, causes acculumlation of 17-hydroxy progesterone and other hormones with androgenic properties. Twenty-one hydroxylase deficiency in female embryos causes androgenic stimulation that results in enlargement of the genital tubercle, fusion of the internal and external urethral folds and fusion of the labio-scrotal folds just as normal production of testosterone does in male embryos. This can result in a female infant having marked enlargement of the clitoris and fusion of the labioscrotal folds. This 'virilization' can cause an infant with a 46-XX karyotype to have the appearance of having hypospadias and cryptrochidism..
Any infant appearing to have virilization failure (proximal hypospadias and non-palpable testes) should be evaluated for congenital adrenal hyperplasia by obtaining a karyotype and measuring 17-hydroxy progesterone.
Females with congenital adrenal hyperplasia have a normal female karyotype (46 XX). They are potentially fertile. By replacing cortisone, the overproduction of androgenic hormones can be decreased. In the past, females affected by congenital adrenal hyperplasia often underwent surgical reconstruction to decrease the size of the clitoris and to widen the vaginal introitus. However, it has become evident that some such individuals are, as adults, displeased with the long-term result (decreased clitoral sensitivity, vaginal stenosis, etc.). As a result, many pediatric urologists, endocrinologists and psychiatrists are recommending that any reconstructive surgery for intersex conditions be undertaken only after the affected individual can understand the ramifications of the surgery and give informed consent.
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©David A. Hatch, M.D., 2003