Cryptorchidism and Hypospadias

Undescended testis (UDT) is a common abnormality, affecting about 1/20 males at birth. Half of these have delayed testicular descent, with the testis in the scrotum by 10-12 weeks after term. Beyond this spontaneous descent is rare. Current treatment recommendations are that UDT beyond 3 months of age need surgery before 12 months of age. Some children have scrotal testes in infancy but develop UDT later in childhood because the spermatic cord does not elongate with age, leaving the testes behind as the scrotum moves further from the groin with growth of the pelvis. This is now known as ascending/acquired cryptorchidism, and orchidopexy is controversial. Many authors recommend surgery once the testes no longer reside spontaneously in the scrotum, but some groups recommend conservative treatment. The fetal testis descends in 2 separate hormonal and anatomical steps, with the first step occurring between 8-15 weeks’ gestation. Insulin-like hormone 3 (INSL3) from developing Leydig cells stimulates the genito-inquinal ligament, or gubernaculum, to swell where it ends in the inguinal area of the abdominal wall. This holds the testis near the future inguinal canal as the fetal abdomen enlarges. By contrast, in female fetuses, lack of INSL3 allows the gubernaculum to elongate into a round ligament and lets the ovary move away from the groin. The second or inguinoscrotal phase is controlled by androgen and occurs between 25-35 weeks’ gestation, where the gubernaculum and testis migrate together to the scrotum. Androgens guide this complex process, both directly and indirectly via a neurotransmitter, calcitonin gene-related peptide (CGRP), released from the genitofemoral nerve. After migration is complete the proximal processus vaginalis closes (preventing inguinal hernia) and then the fibrous remnant disappears completely, allowing the spermatic cord to elongate with age, to keep the testis scrotal. The transabdominal phase is a simple mechanical process, and abnormalities are uncommon, with intra-abdominal testes found in 5-10% of boys with UDT. Anomalies of the complex inguinoscrotal phase account for most UDT seen clinically. The undescended testis suffers heat stress when not at the lower scrotal temperature (33 degrees Celsius), interfering with testicular physiology and development of germ cells into spermatogonia. UDT interrupts transformation of neonatal gonocytes into type-A spermatogonia, the putative spermatogenic stem cells at 3-9 months of age. Recent evidence suggests orchidopexy between 6-12 months improves germ cell development, with early reports of improved fertility, but little evidence yet for changes in malignancy prognosis. Hypospadias is also a common abnormality in newborn males, affecting about 1/150 boys. Androgens control masculinization of the genital tubercle into penis between 8-12 weeks’ gestation, with tubularization of the urethra from the perineum to the tip of the glans. If this process is disrupted hypospadias occurs, with a variable proximal urethral meatus, failed ventral preputial development producing a dorsal hood, and discrepancy in the ventral versus dorsal penile length, causing a ventral bend in the penis, known as chordee. Surgery to correct hypospadias is recommended between 6-18 months, as technical advances now allow operation to be done before the infant acquires long-term memory of the surgery. Severe hypospadias overlaps with disorders of sex development (DSD), so that babies without a fused scrotum containing 2 testes and who present with ‘hypospadias’ need full DSD investigations at birth. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.