Cryptorchidism or undescended testis is the most common disorder of the sexual differentiation, seen in 2—4 % of the male infants at birth. The exact cause of the cryptorchidism is still not known. Early treatment of this condition is necessary to avoid the complications such as infertility, testicular malignancy, torsion, and/or an inguinal hernia in later life. The treatment is essentially surgical which involve repositioning of the testis within the scrotal sac, also known as orchidopexy. The currently recommended timing for orchidopexy is between 6 and 12 months of life. In this article, epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis, evaluation, complications and treatment of undescended testis in children are described.

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Cryptorchidism, undescended testis

Image: “Cryptorchidism, undescended testis” by Nevit Dilmen. License: CC BY-SA 3.0


Definition

Cryptorchidism can be defined as hidden testis or a testis which is not within the scrotum and cannot be manipulated into scrotum without pain. Cryptorchid testis can be absent but most of them are undescended (UDT). Testis may be absent due to agenesis or intrauterine vascular compromise (e.g. torsion). A true or congenital UDT is one which had not previously descended along its normal path.

Ectopic testes (accounts for < 1 % of UDT) descend normally but then are diverted to an aberrant position such as suprapubic region, perineum, femoral canal, superficial inguinal pouch, or contralateral scrotum. Retractile testes are suprascrotal testes which are often misdiagnosed as UDT. Due to brisk cremasteric reflex, it becomes difficult to manipulate testis into the scrotum; although, it can be pulled into the scrotum and remain there if cremasteric reflex is overcome.

Acquired or ascending UDT, recognized more frequently now, is defined as UDT in which previous scrotal position was documented at least once (Hack WW, et al 2003). Usually, testes are present in a scrotal position at birth, but in early childhood (between 4—10 yr), testes “ascend” out of the scrotum. Secondary cryptorchidism can be seen as a complication of inguinal hernia repair in up to 1—2 % of the patients, commonly neonates and young infants.

Epidemiology of Cryptorchidism

Cryptorchidism is more common in premature infants as testicular descent occurs late in gestation. Therefore, up to 30% of premature male newborns have UDT at birth in comparison to 2-5% of full-term infants. Most of the UDT descend spontaneously so that by the age of one year, the prevalence decreases to < 1 %. Spontaneous descent is rare after six months; therefore, the optimal time for surgery is six months of age.

Geographical variation in its prevalence is seen and it varies from 4.3—4.9 % at birth to 1—1.5 % at 3 months to 0.8—2.5 % at 9 months of age. However, the exact reason of this variation is unknown but may be due to genetics or environmental factors. Risk ratios for cryptorchidism are 10.1 in twins, 3.5 in brothers, and 2.3 in offspring of fathers who had a UDT. Cryptorchidism is usually unilateral with a left-sided predominance; however, bilateral UDT is seen in 10 % cases. Most of the UDT are palpable and common locations are suprascrotal (outside the external ring), inguinal canal, and abdomen. Approximately 20 % boys have at least one non-palpable testis which may be intra-abdominal, atrophic, or absent.

Etiology of Cryptorchidism

These include prematurity, low birth weight, small for gestational age, twin pregnancy, breech presentation, and maternal factors (elderly mothers, obesity, diabetes, and estrogen exposure during pregnancy) and family history of cryptorchidism. Genetic susceptibility also exists, but this is likely to be polygenic and multifactorial.

Associated Anomalies

Cryptorchidism is an associated finding in many clinical syndromes e.g. Kallmann syndrome, Noonan syndrome, trisomy 13, trisomy 18, Prader-Willi syndrome, and Laurence-Moon-Biedl syndrome and abdominal wall defects, neural tube defects etc. Co-existing cryptorchidism and hypospadias increase the risk of sex development disorders, such as mixed gonadal dysgenesis.

Pathogenesis of Cryptorchidism

The development of testis begins at 7—8 wk of gestation. At 10—11 wk, Wolffian (mesonephric) duct is differentiated into the epididymis, vas deferens, seminal vesicle, and ejaculatory duct in presence of testosterone. The intraabdominal descent of testis is androgen-independent. By the 28

By the 28th week of gestation, testis starts descending through the inguinal canal. Various hormonal ( a müllerian-inhibiting substance (MIS), testosterone, dihydrotestosterone) and mechanical factors (gubernaculum, intra-abdominal pressure, genitofemoral nerve) help to regulate this process.

At 32—36 wk, gubernaculum anchors the testis at the internal inguinal ring and guide the testis into the scrotum by distending the inguinal canal. Alterations in any of the above-mentioned factors may lead to UDT e.g. gonadotropin deficiency, decreased MIS, and increased estradiol expression in placenta, changes in abdominal pressure, and gubernacular regression. The role of molecular factors e.g. mutations in insulin-like factor-3 is also being studied.

Differential Diagnosis of Cryptorchidism

Differential diagnosis includes retractile, ectopic, or absent testis. Retractile testes can easily be ruled out with thorough history and examination. However, it is difficult to differentiate retractile from ectopic testis. A phenotypically male newborn with bilateral nonpalpable testes should be evaluated to rule out anorchia or a genetic female with congenital adrenal hyperplasia (CAH), or androgen receptor disorders, or disorders of sex development. Surgical exploration often differentiates testicular agenesis and intrauterine torsion as in agenesis, all testicular structures are absent whereas their remnants can be seen in torsion.

Evaluation

History

Try finding the family history of infertility or genital anomalies, and unexplained neonatal death or history of endocrine problems during pregnancy. Try to elucidate the presence of testes in scrotum during the neonatal period.

Physical examination

To look for the features of congenital malformation syndromes.

Genital examination

Look for any abnormality such as hypospadias, hypoplastic or hemiscrotum and inguinal fullness. In infants and young children, the testicular examination should be done with two hands with one hand near anterior superior iliac spine (ASIS) and other on the scrotum. The first hand is swept from ASIS along the inguinal canal towards scrotum. A true undescended or ectopic inguinal testis slides under the examiner’s fingers while low ectopic or retractile testis is felt by the second hand as testis is milked into the scrotum. If the testis is non-palpable, “soap test” is often useful; soap applied to the inguinal canal and hand significantly reduces friction and facilitates identification of inguinal testis.

When after pulling testis into the scrotum, it is held for one minute to fatigue cremasteric muscle. After this maneuver, retractile testis remains in scrotum whereas ectopic testis immediately comes out of the scrotum. Pediatric urologist opinion should be taken to differentiate retractile and true UDT or in presence of palpable, but probably atrophic testis in the scrotum.

Examiner should note the position of testis, its consistency, and size of both testes. If the testis is not palpated in inguinal canal or scrotum or in its usual ectopic sites, evaluation should be done for non-palpable testis.

Radiologic evaluation

It is usually not warranted in the evaluation of nonpalpable testes due to lack of sensitivity and specificity. However, ultrasound may be useful 1) in male newborns with bilateral nonpalpable testes to identify the gonads (testis or uterus) 2) in case of difficulty to feel intracanalicular testes such as in obese boys.

Laboratory evaluation

In phenotypically male newborns with bilateral nonpalpable testes, life-threatening condition CAH must be excluded by following investigations: ultrasound pelvis, karyotype, and measurement of electrolytes, LH, FSH, testosterone, MIS, and adrenal hormones and metabolites (e.g. 17-hydroxyprogesterone). Hormonal evaluation should be done in older children with bilateral nonpalpable testes and elevated gonadotropin levels, absent MIS levels and negative human chorionic gonadotropin (hCG) stimulation test may suggest testicular absence in them. Boys with anorchidism do not respond to hCG, whereas boys with bilateral cryptorchidism respond with increased testosterone production.

Complications of Cryptorchidism

The complications include testicular malignancy, infertility, testicular torsion, inguinal hernia and psychologic effects of empty scrotum. Retractile and absent testicles do not increase these risks. Ectopic testes are prone to trauma leading to decreased spermatogenesis; however, the risk of malignancy is not increased.

Testicular cancer (high yield for USMLE)

Males with UDT have 4 to 10 times more risk of malignancy than the general population with the peak age of 15—45 yr. Approximately 1 in 80 patients with unilateral and 1 in 40 in bilateral UDT has a risk of developing a malignancy. Approximately 10 % of the patients with testicular tumors have a history of UDT. The risk of developing malignancy is four times less in inguinal than with intraabdominal testes.

The most common tumor is seminoma (65 %); however, after surgery, only 30 % of testis tumors are represented by seminoma. The role of early orchiopexy to reduce the risk of testicular malignancy is controversial. However, chances of development of cancers are rare if orchiopexy has been performed before 2 yr of age. The contralateral scrotal testis is not at increased risk for malignancy. Early surgery also permits the earlier detection of testicular masses, improves fertility, and prevents torsion.

Infertility (high yield for USMLE)

These patients have an increased incidence of infertility along with lower sperm counts, and sperms of poorer quality due to the adverse effect of temperature on spermatogenesis. Intraabdominal and intracanalicular UDT are affected similarly. The degree of germ-cell dysfunction is correlated with the duration of the suprascrotal location of the testes and whether one or both testes are affected. In contrast to malignancy, there is a clear advantage to performing early orchiopexy for the protection of fertility. After treatment, 50—65 % of the patients with bilateral UDT and 85 % patients with unilateral UDT are fertile. Orchidopexy should be performed before 1 year of age to minimize infertility (Chung E, et al, 2011).

Testicular torsion

The incidence of torsion is 10 times higher in UDT than in normal scrotal testes. It is more common in neonatal age and after puberty; although, it can occur at any age. Increased weight and distorted architecture of the organ may be the cause of the torsion. Torsion of an intraabdominal testis can present as an acute abdomen. Early diagnosis and surgical treatment can prevent this complication.

An inguinal hernia

Up to 90 % of the UDT have associated inguinal hernia. In untreated cases, it can present with complications e.g. incarceration or strangulation. In symptomatic cases, complete repair with orchiopexy should be done at presentation. Otherwise, orchiopexy should be combined with hernia repair.

Treatment of Cryptorchidism

Treatment can be surgical, hormonal, or a combination of both.

Surgical

The congenital UDT should be treated surgically by 9-15 month of age; even at 6 months as the spontaneous descent is unlikely after 4 mo of age.

Orchiopexy

Surgery of choice for palpable UDT is inguinal orchiopexy, in which testis and spermatic cords are brought into the scrotum and sutured in place along with the correction of an inguinal hernia. The procedure is typically performed on an outpatient basis with a success rate of 98%. The complications of orchiopexy are rare and include testicular atrophy (most significant), the ascent of the testis, infection, and bleeding.

Exploration

Surgery for the non-palpable testis is both diagnostic and potentially therapeutic which can be either open inguinal approach or laparoscopy, latter being preferred. Surgical exploration determines the presence and location of the testis. If the testis is found viable, positioning and fixing within the scrotum is attempted but complete removal is done if it is nonviable. About 50% boys have testis in the abdominal or high inguinal canal while remaining have absent testis. Vanishing testes is a term given to atrophic remnants found in the scrotum or inguinal canal in cases with absent testis. In the majority of the cases, orchidopexy done for intra-abdominal testis (near internal inguinal ring) is successful; however, two-stage orchidopexy is sometimes needed in high abdominal testes. Orchiectomy is reserved for the difficult cases or if testis is atrophic.

To alleviate undesirable psychologic effects due to absent gonads in the scrotum in older children and adolescents, testicular prostheses can be implanted inside the scrotum. The FDA has approved a saline testicular implant; although, solid silicone “carving block” implants are also being used. In boys with anorchia, testicular prostheses should be placed early in the childhood.

Hormonal

Hormonal treatment such as hCG and gonadotropin-releasing hormone (GnRH) is used infrequently. These may stimulate testicular descent by stimulating Leydig cell production of testosterone. In the US, hCG is the only hormone approved for the treatment of cryptorchidism. It is administered intramuscularly, 1500 to 2500 units twice weekly for four weeks. Either of these hormones is not found to be very effective with reported efficacy of 5 to 20% and a relapse rate of 25%. However, it may improve fertility in cryptorchid boys.

American Urological Association Guidelines 2014 (Kolon TF, et al, 2014):

  • Testes should be examined for their position at every well-baby visit.
  • Children with cryptorchidism should be referred by the age of 6 months for further evaluation and management.
  • Immediate consultation should be taken in all phenotypic male newborns with bilateral nonpalpable testes to rule out disorders of sex development.
  • USG or other imaging should not be done prior to the referral to a specialist.
  • Orchidopexy should be done in case of failure to descend spontaneously by 6 months of age.
  • Currently, hormonal therapy has no role in the management of cryptorchidism.
  • Surgical exploration should be done in prepubertal boys with nonpalpable testis and if indicated, abdominal orchidopexy should also be performed.
  • Patients and their parents should be counseled about the risk of infertility and malignancy.

Review Questions

The correct answers can be found below the references.

1. A 6-month old boy was brought by the parents when mother noticed that left side of the scrotal sac is empty. On examination, you were able to pull the testis down to the scrotal sac which remained there. How will you manage this child?

  1. Scrotal orchidopexy
  2. Reassurance and reevaluation
  3. Refer to pediatric urologist
  4. USG pelvis

2. A 2-month-old male baby was brought with complaints of the empty scrotal sac. On genital examination, some mass was felt below the examining finger. How will you manage this case?

  1. Nothing to do, reassure the parents
  2. Order USG pelvis
  3. hCG therapy
  4. Re-evaluate at 6 month

3. A phenotypically male newborn was found to have bilateral non-palpable testes. Which of the disorder should be ruled out immediately?

  1. Congenital Adrenal Hyperplasia
  2. Vanishing Testis
  3. Testicular Torsion
  4. Retractile Testis
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