• Undescended testes

• Hypogonadotropic hypogonadism
  • Boys with cryptorchidism lack the normal post-natal gonadotropin surge at 60 to 90 days. As a result, there is no proliferation of Leydig cells, no testosterone surge, and no maturation of germ cells.
  • Higher incidence of central nervous system (CNS) abnormalities in boys with bilateral cryptorchidism than those with unilateral cryptorchidism or normal testes, possibly related to a pituitary abnormality causing hypogonadotropism
• Gubernaculum also influences testicular descent, possibly due to innervation by the genitofemoral nerve, which promotes descent
  • Only 17% of cryptorchid testes have normal gubernacular attachment
• Different possible locations of a cryptorchid testis:
  • Intra-abdominal—at least 1 cm above internal inguinal ring
  • High annular—just at internal ring
  • Canalicular
  • Within superficial inguinal pouch of Denis Browne—the most common location
  • High scrotal
  • 25% are descended testes missed by palpation
  • 20% absent
  • Ectopic testes have taken an aberrant course of descent—prepenile, superficial ectopic, transverse scrotal, femoral or perineal location

• Cryptorchid testes have normal histology at birth.
• By 1 year of life there is atrophy with lack of development.
• By 2 years of life there are greatly reduced numbers of germ cells due to increased temperatures and the damage appears to be irreversible.
• Undescended testes are smaller than descended; damage is irreversible.
• More histological changes are noted the higher the testis is located.
• Some germ cell loss is also noted in the contralateral descended testis; up to 40% of contralateral descended testes may have decreased germ cells if the undescended testicle is not corrected.

• Incidence greater in premature infants and low birthwieght infants—3.4% in full-term; 17% in premature infants weighing 2 to 2.5 kg; 100% in infants, 900 g.
  • Normal descent occurs in the seventh month of gestation.
• 0.7% incidence in children. 1 year old and adults
  • Post-natal increases of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) may result in late descent that occurs in about 50% of cryptorchid testes in first 12 months.
  • Spontaneous descent does not appear to occur beyond 1 year.
  • Most descend by 3 months of age; for premature babies, within 3 months of their due date; the post-natal surge of gonadotropin and testosterone play an important role in the descent of testes in the first 3 months of life.
  • 70% descend by 1 year
• 66% of boys with cryptorchidism may have retractile testes
• 30% are bilateral

• Incidence of 1% to 4% in siblings of boys with cryptorchidism
• 6% of fathers of boys with cryptorchidism had cryptorchidism
• Increased incidence in disorders of gonadotropin deficiency (i.e., Kallmann, Prader-Willi, Lawrence-Moon-Biedl syndromes)
• Also increased incidence in Klinefelter and Noonan syndromes, and neural-tube disorders

• Retractile testes—normally descended testes that may be noted on initial physical examination because the cremasteric reflex is weak.
  • Subsequently, may be difficult to palpate because of exaggerated cremasteric reflex at about 3 months of age; may be bilateral
  • Testes are positioned outside of scrotum, but can be brought down into and remain in the scrotum with out tension
  • Human chorionic gonadotropin (hCG) stimulation test often results in descent
  • Normal-sized testes with normally developed scrotum
  • Histologically normal
  • Testes usually remain in the scrotum by early puberty
• If testes are not palpable, absent testes must be considered:
  • 20% of undescended testes are not palpable—50% are inguinal, 25% intra-abdominal, 15% below the external inguinal ring, 10% absent
  • 45% of non-palpable testes are due to absent gonad
  • Anorchia occurs in 5% of bilateral cryptorchidism
  • Usually occurs due to vascular accident prenatally or soon after birth—analogous to testicular torsion
  • Spermatic vessels and vas deferens end blindly in inguinal canal or scrotum.
  • 48% to 59% of unilateral non-palpable testis are due to testicular absence associated with significant contralateral hypertrophy of testis

Finding: Non-palpable testes
Significance: Repeated annual examination is necessary, however, because descended testes may spontaneously come to occupy an extrascrotal position where it is prone to the same degenerative changes seen in cryptorchidism

Finding: Associated hypospadias with unilateral or bilateral cryptorchidism
Significance: Increases the risk of an intersex disorder such as mixed gonadal dysgenesis or male pseudohermaphroditism

Finding: Bilateral non-palpable gonads
Significance: Should trigger evaluation for anorchia, female androgenital syndrome, or hypothalamic-pituitary insufficiency

• To detect retractile testes, use a warm room, and seated, cross-legged, or squatting position.
• Begin palpation in the area of internal inguinal ring, and walk fingers down the canal toward the scrotum.
• Lubricating jelly may help decrease friction.

Test: hCG Stimulation
Significance: Normal response of testicular tissue is a fourfold increase in serum testosterone. No response in anorchia.

Test: Basal gonadotropin levels
Significance: These are 3 standard deviations above the mean in anorchia in boys<9 years old.

Test: Anorchia
Significance: This is also associated with elevated LH and FSH levels.

Test: Venography
Significance: Is successful in locating testes in 75% of cases of non-palpable testes, but is limited by size of gonadal vessels to older children.

Test: Laparoscopy
Significance: This is 95% accurate in locating non-palpable testes.

• Ultrasound and CT scanning have been useful in older boys, although MRI seems to be more accurate.

• Hormonal therapy involves use of hCG and/or gonadotropin-releasing hormone (GnRH) to bring down testes by stimulating testosterone but without inducing pubertal changes.
  • GnRH has few side effects and does not cause virilization, but is not approved for use in the United States.
  • GnRH alone results in descent in 28% in studies in Europe
  • hCG successful in 10%, but relatively ineffective for intra-abdominal testes
  • Bilateral cryptorchidism is more responsive to hCG therapy than unilateral
  • 10% to 20% ascend after hCG therapy, requiring a repeat course or surgery
  • Combination of GnRH followed by hCG is successful in 80%
  • Combined use produces better results than monotherapy; best results in low-lying testes
  • 50% relapse rate at 7 years
  • Hormonal therapy may improve future fertility
  • Recommended doses are biweekly injection of 250 IU hCG for infants, and 500 IU up to age 6 years and 1000 IU for older children for a total course of 5 weeks.
  • Therapy must be initiated by 10 months of age so that treatment failures can be referred for orchiopexy.
  • Side effects of hCG include epiphyseal plate fusion, accelerated development of secondary sex characteristics and retarded growth with large doses.

• Goal is to locate testis and to relocate the testis to the scrotum if possible:
  • Options include traditional orchiopexy or microvascular autotransplantation.
  • Surgery recommended between 6 and 18 months because of progressive damage that occurs to testes with time.
  • Complications—injury to the vas deferens may affect fertility.
• Laparoscopy can be both diagnostic and therapeutic—if spermatic cord and vessels end blindly, no additional exploration necessary.
• If testes are intra-abdominal, orchiectomy is recommended because of future cancer risk.

• Infertility if bilateral and untreated
  • If bilateral and treated—50% are fertile
  • If unilateral and treated—75% are fertile
  • Earlier orchiopexy may improve fertility, but there are conflicting data
• Risk of cancer is 22 × greater than the general population in third or fourth decade in undescended testes, especially if untreated or corrected after or during puberty:
  • Risk is increased sixfold if testis is intra-abdominal versus other cryptorchid locations
  • 60% of tumors of undescended testes are seminomas
  • Cancer is rare before puberty
  • 25% of tumors occur in contralateral normally descended testis
  • No evidence that orchiopexy alters malignancy potential, but orchiopexy renders testis accessible for regular self-examination
  • Earlier age at orchiopexy reduces the excess risk of malignancy
• Carcinoma in situ found in 2% to 3% of all men with a history of cryptorchidism:
  • Treat with orchiectomy or radiation
  • Ultrasonography may be used to screen for irregularities indicative of carcinoma in situ
  • Invasive cancer develops in 50% in 5 years.