Endocrine evaluation of hypospadias.

Abstract

Hypospadias is a congenital defect of the penis resulting in an incomplete development of the anterior urethra (Duckett, 1998). The abnormal urethral opening may be any place along the shaft of the penis or open onto the scrotum or perineum. By the end of the first month of gestation, the hindgut reaches the surface of the embryo at the cloacal membrane on the ventral surface. The cloacal membrane is then divided by the urorectal septum into the anal and urogenital membrane. The genital tubercle and genital swellings appear around the urogenital membrane. A surge of luteinizing hormone from the pituitary gland leads to an increase of testosterone. Testosterone biosynthesis occurs at about 9 weeks gestation and hCG-LH receptors are present on fetal Leydig cells by at least 12 weeks of gestation. Androgens are critical for the induction, growth and differentiation of the genital tubercle into the male phenotype via the androgen receptor (AR), a nuclear transcription factor. Dihydrotestosterone, a metabolite of testosterone, mediates the action of androgens on the external genitalia and is known to bind to the AR with a higher affinity than testosterone. Masculinization of the external genitalia, namely elongation of the phallus, formation of the penile urethra from the urethral groove and development of the prepuce, depends on adequate testosterone synthesis, adequacy of the enzymatic pathway mediating the cascade and responsive end organs. During the third fetal month, the wolffian ducts complete their development and involution of the mullerian system occurs under the influence of mullerian inhibiting substance (MIS or AMH). A deficiency in the formation or delay in the maturation of the enzymes in the testosterone steroid cascade during these critical embryogenesis periods may be responsible for incomplete development.