Etiology

Etiology is unknown at present. However, several etiologic factors have been suggested:

  • Hormonal: patients may have abnormalities in the pathways/signaling of testosterone, mullerian inhibiting substance, insulin-like 3 hormone or its receptor LGR8, epidermal growth factor, and/or estrogens.[9][10][11]

  • Environmental or maternal toxins: organochlorines, environmental estrogens, phthalate esters, and pesticides have all been linked to increased risk of cryptorchidism, though current literature is inconclusive.[5][8][12][13][14][15][16][17]

  • Maternal alcohol consumption, analgesic consumption, and smoking have also been associated with an increased risk, though these data are conflicting.[18][19][20][21][22]

  • Gestational diabetes and/or obesity may be related to the development of cryptorchidism.[22]

  • Genetic: up to 23% of cases have been associated with familial clustering, suggesting an underlying genetic mutation as the etiology in these patients.[23][24] Specific mutations include mutations involving insulin-like factor 3 and its receptor, LGR8, and CAG/GGC repeats in androgen receptor genes.[25][26][27][28] Approximately 3% of boys with isolated cryptorchidism have a chromosomal anomaly.[29][30]

  • Mechanical: problems with development of the gubernaculum or cremasteric muscle fibers, a patent processus vaginalis, or impaired intra-abdominal pressure have also been hypothesized to contribute to cryptorchidism.[11][31][32][33]

  • Neuromuscular: abnormalities of the calcitonin gene-related peptide of the genitofemoral nerve or the cremasteric nucleus have been postulated to cause cryptorchidism.[34]

Pathophysiology

In most infants affected with cryptorchidism, the underlying pathophysiology is thought to be incomplete migration of the testis during embryogenesis from the original retroperitoneal position near the kidneys to its final position in the scrotum. This occurs in both androgen-dependent and androgen-independent phases.[34] Less commonly, the underlying etiology is either absent testis or severely atrophic testis (nubbin), usually thought to be secondary to malformation or the result of testicular torsion.

Classification

Consensus on treatment of undescended testes[1]

Undescended, palpable testis, age over 6 months

  • Retractile testis: can be manipulated into the scrotum and remains in the scrotum upon release of traction

  • Cryptorchid testis: unable to be pulled into scrotum or immediately returns to higher position after being manipulated into the scrotum.

Unilaterally nonpalpable testis:

  • Unable to locate testis despite thorough physical exam.

Bilaterally nonpalpable testes (refer immediately for a disorder of sex development (DSD) workup):

  • Associated with normal penis

  • Associated with micropenis or hypospadias.

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