Cryptorchidism

An undescended testis (cryptorchidism) is the most common genital abnormality seen in male newborn infants. It occurs in 3% of babies. Either one or both testes may be involved. Cryptorchidism occurs when the gubernaculum fails to develop or fails to pull the testes into the scrotum. Androgen activity directs gubernacular development and function, thus gubernacular dysfunction reflects androgen abnormalities. Insufficient androgen activity can result from developmental defects anywhere along the fetal hypothalamic–pituitary–testicular axis. To this point, cryptorchidism can result from any of the following: (i) fetal hypothalamic failure to stimulate gonadotropin secretion in the third trimester (Kallmann and Prader–Willi syndromes, anencephaly); (ii) failure of the testes to secrete androgens (gonadal dysgenesis); (iii) failure of testosterone conversion to dihydrotestosterone (DHT) in target tissues (5α-reductase deficiency); or (iv) absence of functioning androgen receptors (androgen insensitivity syndromes) (Table 26.1).

Table 26.1 The androgen insensitivity syndromes

Cryptorchid testes may remain in the inguinal canal (70%), the abdomen or retroperitoneum (25%), or other ectopic locations (5%). Testes remaining in the abdomen or inguinal canal will be exposed to comparatively higher temperatures than those in the scrotum and will cease spermatogenesis in response. They are also prone to neoplastic change. Medical therapy for cryptorchidism involves administration of human chorionic gonadotropin (hCG) or androgens. Surgical therapy is called orchiopexy. Some cryptorchid testes are unresponsive to medications or cannot be brought into the scrotum surgically. These testes are usually removed because they cannot be adequately monitored for the development of a neoplasm.

Inguinal hernia is a forme fruste of cryptorchidism. Here, testicular descent occurs, but the inguinal ring does not close completely after descent. Boys who have an inguinal hernia diagnosed before the age of 15 have twice the risk of developing testicular cancer when compared to boys in the general population.

Hypospadias

Hypospadias is a very common congenital abnormality seen in male newborn infants. In hypospadias, the urethral meatus opens on to the ventral surface of the penile shaft at sites proximal to the normal location (Fig. 26.1). Embryologically, hypospadias results from a failure of complete ventral closure of the urethral groove. The penile urethra depends on the androgen DHT to differentiate. Therefore, hypospadias can result from deficiencies in testosterone (T) production, from inadequate conversion of T to DHT, or from local deficiencies in androgen recognition (insufficient androgen receptor number or function). There is a non-Mendelian genetic predisposition to hypospadias. If one sibling has a hypospadias, the recurrence risk is 12% in that family. If both the father and a brother are affected, the risk for a second son is 25%.

Cryptorchidism is seen in 16% of boys with hypospadias. If both are present, the child may be a pseudohermaphrodite and chromosomal and hormonal testing should be obtained.

Congenital bilateral absence of the vas deferens

Congenital bilateral absence of the vas deferens (CBAVD) is a rare congenital anomaly found most often in men with cystic fibrosis (CF). It can also occur in the absence of clinically apparent CF. When it does, it is usually associated with mutations in the gene coding for the CF transmembrane receptor (CFTR). The molecular mechanism by which an abnormal transmembrane receptor involved in chloride channels leads either to failure of the vas deferens to differentiate or to its resorption is not known. The presence of CBAVD mandates genetic testing for CF genes.

Microorchidism

The presence of at least one additional X chromosome in most of the cells of a man with Kleinfelter syndrome (usually 47XXY) results in hypogonadism and frequent infertility and microorchidism. XXY men are variably affected with other physical (tall stature, gynecomastia) and behavioral (speech and learning) problems. This is the most common sex chromosome aneuploidy in males and may be one of the most common chromosome abnormalities in humans.