Endocrine studies in patients with advanced hypospadias

We evaluated 15 boys less than 4 years old with advanced degrees of hypospadias for the presence of an endocrinopathy by a variety of special tests. There were 6 different endocrine-related abnormalities uncovered in 11 patients. One child had been exposed to progesterone given to the mother during the first trimester of pregnancy, 1 had an abnormal karyotype and 1 had an absent gonad on 1 side. One patient with a family history of Reifenstein's syndrome had low receptor numbers and 3 patients exhibited a poor genital response to exogenous testosterone despite normal receptor levels. However, the most striking finding was that of a poor testosterone response to human chorionic gonadotropin injections, which was seen in 7 patients. In several instances this improved with time and even normalized in 2 patients. This experience suggests that hypospadias is a local manifestation of an endocrinopathy rather than a local dysmorphic problem, and that 1 major cause of it may be a delay in maturation of the hypothalamic-pituitary-testicular axis.