Syndromes of Abnormal Sex Differentiation

V. Summary

Sexual differentiation refers to the physiological development of a fetus along male or female lines. Disorders of sexual differentiation, or syndromes of intersexuality, result when errors occur at any of these steps. This booklet is organized to serve as a basic explanation of the process of normal sexual differentiation, and it is also meant to explain the deviations from normal development underlying several syndromes of sexual differentiation.

Endocrine Treatment

1. What is the procedure for identifying and treating intersex syndromes in newborns?

When a child with an intersex syndrome also has ambiguous (undifferentiated) external genitalia, the syndrome is usually identified at birth. We recommend that a team consisting of a pediatric endocrinologist, gynecologist, urologist, geneticist and psychologist experienced in dealing with intersex conditions work together to treat these children.

Although difficult for parents, it is important not to assign a sex to an affected newborn until after proper diagnosis is agreed upon by the parents and team of doctors. We think this because it is more difficult for families to reassign a baby's sex than to postpone an initial assignment until after a diagnosis is agreed upon.

The examinations and laboratory tests necessary for attempting to establish a diagnosis may take several days. During that time, we advise parents to report to well-wishers that the infant was born with incompletely developed genitalia, and that it may take several days before the sex of the baby can be determined.

Until a diagnosis is made, it is important to use neutral terms such as baby, gonad and phallus instead of sex-specific terms like boy or girl, testes or ovaries and penis or clitoris. By using neutral terms, it is easier for families to adopt the appropriate sex of assignment for the child after a diagnosis has been made.

The following chart shows the recommended schedule for diagnostic tests and examinations for establishing a diagnosis as quickly and as accurately as possible.

The karyotype determines if a child is 46,XX, 46,XY, or a variant of the two. Androgens should be measured on Day 2 because the concentrations of these hormones decrease after that time. 17-hydroxyprogesterone, progesterone and androstenedione may be elevated after birth, but by Day 3 it is possible to detect abnormal concentrations of these hormones. Both a sonogram and genitogram allow physicians to determine which parts of the Mullerian and Wolffian duct system are present, and where they are located. In some cases, a stimulation test with human chorionic gonadotropin (HCG) is used to determine the nature of steroid secretion of the gonads, particularly if the exam is after 3 months of age. Studies on Day 5 will confirm values obtained on previous days. Finally, it is extremely important to closely monitor weight, serum electrolytes and blood glucose levels to assure that the newborn will not experience an adrenal crisis, a common occurrence in some syndromes of sex differentiation.

2. What is the procedure for identifying and treating intersex syndromes in older children?

While we recommend that sex assignment be postponed until after a diagnosis is made for a newborn with an intersex syndrome, older infants or children will have already lived as either a boy or girl regardless of diagnosis. In such instances, it is usually best to continue with the original sex assignment because such a change is often unsuccessful if it occurs after the first 18 months of life. We feel that sex reassignment within the first month of life is most likely to be successful if such a change is determined necessary by parents and doctors. For most older children, a reassignment should only be considered if desired by the child.

After 3 months of age and before puberty, one often uses an HCG test to determine if the gonad can secrete androgens. This is accomplished by administering a series of injections of human chorionic gonadotropin (HCG).