Undescended testis-10 Interesting Facts

What is Undescended testis

Interesting Facts

  1. Undescended testis or cryptorchidism is characterized by the absence of 1 or both testes from the scrotum
    • Undescended testis may be congenital or acquired and unilateral or bilateral
    • Undescended testis may be located in an intra-abdominal, inguinal, fixed position just outside of the external inguinal ring (prescrotal), superficial inguinal pouch, or other ectopic location
  2. Spontaneous testicular descent of congenital undescended testis occurs by age 6 months (corrected for gestational age) in most cases; spontaneous testicular descent is unlikely after age 6 months (corrected for gestational age) and requires referral to urologist 1 2
  3. Isolated unilateral cryptorchidism is most common; bilateral cryptorchidism may rarely occur in association with a genetic syndrome, disorder of sexual development (eg, congenital adrenal hyperplasia, ovotesticular disorder, gonadal dysgenesis, hypogonadotropic hypogonadism), or anorchia
  4. Unilateral cryptorchidism is best diagnosed by physical examination by an expert examiner; examination under anesthesia is the next step in the evaluation of cryptorchidism
  5. Assess for disorders of sexual development in children with unilateral undescended testis associated with phallic abnormalities, bilateral cryptorchidism, or otherwise ambiguous genitalia; further diagnostic studies to evaluate for hypogonadism and disorders of sexual development are necessary 1 3
  6. Infants with concern for disorders of sexual development require specialized work-up (eg, karyotype, specialized genomic testing, hormone levels, surgical exploration) and consultation with a specialty team trained in individualized evaluation of infants with possible disorders of sexual development (eg, pediatric endocrinologist, pediatric urologist, geneticist)
  7. A truly nonpalpable testis requires surgical exploration to determine location and best approach for surgical correction 1
  8. Orchiopexy is indicated within the first 18 months of life (corrected for gestational age) for congenital cryptorchidism or shortly after diagnosis in older patients 1
  9. Complications of untreated cryptorchidism include testicular cancer, testicular torsion, and infertility
  10. Normal testicular volume and function can be achieved if cryptorchidism is corrected before age 18 months (corrected for gestational age); risk for malignancy is diminished but not eliminated by orchiopexy 2 4

Pitfalls

  • Failure to immediately refer patients with bilateral cryptorchidism to pediatric urologist and pediatric endocrinologist for appropriate evaluation and treatment can result in increased morbidity and mortality from missed diagnosis (eg, disorders of sexual development, congenital syndromes)
  • Refer any patients in whom there is difficulty differentiating between retractile testis and undescended testis to a pediatric urologist; expert examination, sometimes under anesthesia, is occasionally required to differentiate a retractile testis from an undescended testis to determine need for orchiopexy
  • Avoid radiographic imaging before referral for expert examination or examination under anesthesia; imaging does not often contribute to management decisions
  • Failure to adequately examine children yearly for acquired cryptorchidism can lead to increased morbidity and mortality, especially in children at high risk of acquired cryptorchidism (eg, retractile testis, history of delayed testicular descent, previous inguinal surgery, history of proximal hypospadias)
  • Failure to adequately examine yearly and encourage patient monthly testicular self-examinations in patients after orchiopexy can lead to missed testicular malignancy, as surgical correction for cryptorchid testis diminishes but does not eliminate the increased risk of testicular malignancy

Urgent Action

  • Infants with bilateral cryptorchidism or ambiguous genitalia require urgent evaluation for congenital adrenal hyperplasia with serum glucose/electrolyte measurement, karyotype analysis, and multidisciplinary team consult with pediatric urologist and pediatric endocrinologist
  • Children with undescended testis are at increased risk of torsion; prompt consultation with urologist is indicated in any child with undescended testis who presents with severe abdominal or groin pain
  • Children with undescended testis in the inguinal canal are at increased risk of incarcerated or strangulated hernia; prompt consultation with urologist is indicated in any child with undescended testis who presents with severe abdominal or groin pain

Terminology

Clinical Clarification

  • Undescended testis (unilateral cryptorchidism) is characterized by the absence of 1 testis from the normal anatomic position in the scrotum 1
  • Bilateral undescended testes (bilateral cryptorchidism) is characterized by the absence of both testes from the scrotum 1
  • Some cases of apparent cryptorchidism are later determined to be anorchidism via agenesis or resorption (vanishing)

Classification

  • Based on location 1
    • Abdominal testis
      • Intra-abdominal location (eg, peeping through or proximal to the internal inguinal ring; near the bladder, iliac vessels, or kidney)
    • Canalicular testis
      • In the inguinal canal
    • Prescrotal testis (suprascrotal or gliding testis)
      • Above or at the scrotal inlet
      • Testis can be repositioned into the lower scrotum with gentle manipulation but immediately retracts from normal anatomic position following release from manipulation
    • Superficial inguinal pouch
      • Distal and lateral to the external inguinal ring, anterior to the rectus muscle
    • Prepubic testis
      • At the external inguinal ring
    • Ectopic testis
      • Aberrant course of descent after leaving inguinal canal
      • Most common position is perineal; other positions include femoral, pubopenile, or crossed scrotal
  • Based on time of development 1
    • Congenital undescended testis
      • Testis located in extrascrotal position from birth
      • Disorders of sexual development (ie, anatomic sex and hormonal sex discordant with sex chromosomes) can present with bilateral undescended testes, unilateral undescended testis with hypospadias, or otherwise ambiguous genitalia 5
        • Disorders of sexual development include diagnoses such as gonadal dysgenesis, hypogonadotropic hypogonadism, ovotesticular disorder, and congenital adrenal hyperplasia
      • Congenital syndromes that occur in association with cryptorchidism often present with bilateral disease
    • Acquired undescended testis (ascended testis) 6
      • Testis has intrascrotal location at birth then secondarily ascends to a extrascrotal position sometime after birth and remains undescended during childhood

Diagnosis

Clinical Presentation

History

  • Testis is not noted in scrotum immediately after birth
    • Parents may report spontaneous descent of previously undescended testis at birth within the first 6 months of life (corrected for gestational age) 7
      • Approximately 3.7% of all male infants will present with undescended testis at birth, declining to approximately 1% prevalence at 3 months (corrected for gestational age) 8
      • Spontaneous testicular descent is unlikely after age 6 months (corrected for gestational age) 7
  • Parents may report a previously intrascrotal location of testis
    • Testis may ascend out of the scrotum in 1% to 7% of children, with peak incidence around age 8 years 1
    • Testicular ascent occurs more frequently in children who have a history of inguinal surgery, delayed testicular descent (ie, undescended at birth, followed by spontaneous descent, then reascent), retractile testis, or proximal hypospadias
  • Family history may be positive for undescended testis or a genetic condition associated with undescended testes

Physical examination

  • General
    • Most often infant or child is normal appearing with normal postnatal development and good postnatal weight gain, unless a comorbid genetic syndrome is present
    • Infants may be small for gestational age, premature, or low birth weight 8
    • Children with congenital syndromes typically exhibit a variety of abnormal morphologic features associated with their respective syndromes
  • Phallus examination
    • Abnormal phallus (eg, hypospadias, micropenis) or ambiguous genitalia may be observed; typically associated with certain comorbidities (eg, genetic syndromes, disorders of sexual development, anorchia)
    • Micropenis is defined as a stretched penile length of less than 2 to 2.5 cm in a full-term neonate 9
  • Scrotal examination
    • Minimally rugate and hypoplastic in many patients with undescended testis
    • Bifid scrotum is associated with disorders of sexual development 10
  • Testicular examination
    • Unilateral disease
      • Testis is not palpable low in scrotum; left side is affected more frequently
      • Palpable
        • Approximately 70% to 80% of undescended testes are palpable in abnormal anatomic positions on initial examination, including the following locations: 1 7
          • Upper scrotum in up to 45% of cases 7
          • Inguinal canal in up to 20% of cases 7
          • Inguinal superficial pouch in up to 30% of cases 7
          • Perineal or thigh position in up to 5% of cases 7
      • Nonpalpable
        • Approximately 20% to 30% of undescended testes are not palpable on initial physical examination and are located in the following areas: 1 7
          • Intra-abdominal in up to 55% of cases 1
          • Inguinal-scrotal area in up to 30% of cases 1
          • Absent (agenesis or vanishing testis from intrauterine torsion) in up to 15% of cases 1
      • Compensatory testicular hypertrophy (length greater than 2 cm in prepubertal young boys) is highly associated with monorchism; 1 normal full-term testicular volume is approximately 1.1 mL 9
    • Bilateral disease
      • Approximately 20% to 30% of infants with cryptorchidism present with both testes not palpable low in the scrotum 1
      • Children with disorders of sexual development and congenital syndromes present with bilateral cryptorchidism more often than with unilateral cryptorchidism 11
  • Inguinal examination
    • Inguinal fullness may be present with aberrant testicular location in the inguinal area
    • Inguinal hernia is commonly associated with undescended testis (eg, open external inguinal ring)

Causes and Risk Factors

Causes

  • Exact causes of cryptorchidism are unknown

Risk factors and/or associations

Age
  • Congenital undescended testis is most commonly noted in infants 1
    • Occurs in 1% to 3% of full-term males; 1 incidence reduces to about 1% by age 1 year 12
    • Occurs in almost one-third of preterm males 13
  • Incidence of acquired undescended testis is 1% to 7% of male children and peaks at age 8 years 1
Genetics
  • Unknown genetic factors contribute to risk of undescended testis, as evidenced by increasing risk with affected family members 1
    • 2.4% to 4.3% for half brothers
    • 7.5% for full brothers
    • 16.7% for dizygotic twins and 26.7% for monozygotic twins
  • A family history of cryptorchidism increases overall risk 3.6-fold 14
  • Genetic syndromes associated with cryptorchidism include:
    • Prune-belly syndrome (ie, Eagle-Barrett syndrome) (100% of patients) 15
    • Noonan syndrome (50% of patients) 11
    • Klinefelter syndrome (27% of patients) 11
    • FG syndrome (24% of patients) 11
    • Down syndrome (6.5% of patients) 16
    • Other syndromes that carry increased risk for disease include Beckwith-Wiedemann syndrome, Smith-Lemli-Opitz syndrome, de Lange syndrome, and Prader-Willi syndrome 17
Ethnicity/race
  • Asian populations have an increased odds ratio of 3.9 18
  • Black and Hispanic populations have an increased odds ratio of 2.05 18
Other risk factors/associations
  • Low-birth-weight and small-for-gestational age infants 1
    • 1.1% to 45.3% of all male newborns with a weight less than 2.5 kg are diagnosed with undescended testis, as opposed to only 1% to 4.6% of male neonates weighing more than 2.5 kg 1
  • Premature birth
    • Up to 30% of premature boys born before the gestational age of 37 weeks have undescended testis compared with 1% to 3% of full-term males 1 19
  • Other risk factors:
    • Breech presentation at birth 3
    • Cerebral palsy
    • Myelomeningocele or other neural tube defect 3
    • Preexisting retractile testis, 3 history of proximal hypospadias, 1 previous inguinal surgery increase, and history of delayed testicular descent (ie, undescended at birth, followed by spontaneous descent) increase risk for acquired undescended testis
    • Maternal characteristics during pregnancy
      • Advanced maternal age 3
      • Maternal diabetes 3
      • Swollen legs or feet 18
      • Exposure to the following substances:
        • Cola-containing drinks 18
        • Analgesics 18
        • Xenoestrogens, phytoestrogens, or estrogen-mimicking compounds 20
    • Season 1
      • Peak incidence in March in European countries
      • In the United States, incidence peaks twice: from September to November and March to May
    • Birth order
      • More common in first- and second-born boys 21
  • Disorders of sexual development are associated with cryptorchidism (eg, congenital adrenal hyperplasia, ovotesticular disorder, gonadal dysgenesis, hypogonadotropic hypogonadism)
    • Disorder of sexual development is defined as a congenital discrepancy between external genitalia and chromosomal sex (eg, patients with ambiguous genitalia) 22
  • Other associated congenital anomalies in patients with cryptorchidism include: 23
    • Abnormalities in caudal or midline development (eg, imperforate anus, T10 to S5 spine abnormalities)
    • Abnormalities of urogenital system (eg, ipsilateral kidney and ureter)
    • Congenital subluxation of the hip 21

Diagnostic Procedures

  • From Tasian GE et al: Diagnostic imaging in cryptorchidism: utility, indications, and effectiveness. J Ped Surg. 46(12):2406-13, 2011, Figure 3.Suggested algorithm for evaluation and treatment of a boy with cryptorchidism without the need for imaging.

Primary diagnostic tools

  • Diagnostic approach to patients with suspected cryptorchidism depends on physical examination findings (eg, unilateral or bilateral disease, palpability of testis, presence of other associated genital abnormalities) and age of patient
  • Unilateral nonpalpable testis
    • Physical examination with adequate technique and experienced examiner is the primary diagnostic tool 24
      • Pediatric urologist will identify 84% of undescended testis cases on physical examination as compared with 53% by referring physician 3
      • Consult a pediatric urologist as follows to assist with diagnostic considerations and approach:
        • Immediately for neonates with any phallic abnormalities (eg, hypospadias, micropenis, ambiguous genitalia)
          • Karyotype and gender of infant must be determined
        • By age 6 months (corrected for gestational age) in infants with unilateral nonpalpable testis 1
        • At time of diagnosis for children with acquired unilateral nonpalpable testis
        • Immediately in postpubertal patients discovered to have nonpalpable testis
    • Patient with normal phallus
      • Examination under anesthesia at age 6 months (corrected for gestational age) is the initial step in the diagnostic evaluation of congenital cryptorchidism when an experienced examiner is unable to palpate testis 1
      • Examination under anesthesia for children with acquired undescended testis at time of initial observation is the initial step in the diagnostic evaluation for acquired cryptorchidism when an experienced examiner is unable to palpate testis 1
      • Surgical exploration is the gold standard for locating a truly nonpalpable unilateral testis to evaluate for undescended testis (eg, abdominal, inguinal, or ectopic location), testicular agenesis, and vanishing testis 1
    • Newborn with phallic abnormalities (eg, hypospadias, micropenis), ambiguous genitalia, or bifid scrotum 1
      • Immediately consult a pediatric urologist and pediatric endocrinologist for diagnostic and treatment recommendations
      • Obtain karyotype to evaluate for disorders of sexual development with increasingly severe phallic abnormalities
      • Consider dysmorphology or genetics consultation and chromosomal analysis to evaluate for presence of congenital syndromes
  • Bilateral nonpalpable testis
    • Surgical exploration is the primary diagnostic tool in otherwise normal genotypic male patients found to have truly nonpalpable bilateral undescended testes (ie, after anorchia, congenital adrenal hyperplasia, and other disorders of sexual development are excluded) 1
      • Laboratory evidence of functional testicular tissue includes a positive testosterone response to hCG stimulation, low serum FSH level, and inhibin B level within reference range 21
    • Phenotypic newborn male with bilateral nonpalpable testes with or without abnormal phallus or ambiguous genitalia 1
      • Immediately consult an appropriate specialist (eg, specialized treatment team with pediatric urologist and pediatric endocrinologist) for all phenotypic male newborns with bilateral nonpalpable testes for further individualized evaluation 1
        • Circumcision is contraindicated until after evaluation for disorder of sexual development is complete, even if the phallus is normal in patients with bilateral cryptorchidism (ie, infant may actually be virilized genotypic female with congenital adrenal hyperplasia) 1
        • Fully evaluate for disorders of sexual development and congenital syndromes in patients with bilateral cryptorchidism, especially with associated phallic abnormalities (eg, hypospadias, micropenis) 1
        • Save an additional sample of serum from all infants under investigation for ambiguous genitalia or disorders of sexual development for future testing 9
      • Evaluate for congenital adrenal hyperplasia first; follow with tests to evaluate for bilateral anorchia, other disorders of sexual development, congenital syndromes associated with undescended testis, and finally nonpalpable bilateral undescended testes without other associated abnormalities 1
        • Perform a baseline glucose and electrolyte measurement to assess for life-threatening metabolic abnormalities requiring urgent attention that are associated with congenital adrenal hyperplasia; frank salt wasting is uncommon in the first week of life 9
        • Perform karyotype (ie, routine chromosomal analysis) urgently to determine if neonate is male or virilized female; consider array comparative genomic hybridization analysis if karyotype is normal but chromosomal abnormality or mosaicism is still suspected; follow with SRY gene testing in consultation with subspecialty team 5
        • Consider ultrasonography in consultation with pediatric urology recommendations to evaluate internal anatomy (eg, determine if uterus is present) and position of gonads in patients presenting with nonpalpable testis associated with phallic abnormalities (eg, micropenis, hypospadias), with ambiguous genitalia, and with discordant genitalia and chromosome compliment 5
        • Perform serum hormone levels including 17-hydroxyprogesterone, luteinizing hormone, follicle-stimulating hormone, testosterone, and androstenedione; obtain antimüllerian hormone (müllerian inhibiting substance) and inhibin B levels on all patients with an XY karyotype
          • Consider the following diagnoses based on karyotype and results of initial hormone testing:
            • Classic congenital adrenal hyperplasia in a virilized 46,XX infant with high 17-hydroxyprogesterone level 1
            • 46,XY infants
              • Bilateral anorchia presents with absent or low testosterone level, elevated luteinizing hormone and follicle-stimulating hormone levels, and absent antimüllerian hormone (müllerian inhibiting substance) and inhibin B levels 1
              • Hypogonadotropic hypogonadism (eg, Kallmann syndrome or idiopathic gonadotropin-releasing hormone deficiency) presents with low testosterone level, low luteinizing hormone level, and low follicle-stimulating hormone levels 25
            • Ovotesticular disorder and gonadal dysgenesis occur with variable karyotyping profiles including mosaic arrangements 26
              • Hormonal testing is often inconclusive and depends on degree and distribution of gonadal function
              • Screen for known genetic associations with sophisticated genetic testing (eg, chromosome microarray analysis to identify DMRT1 deletions, fluorescence in situ hybridization analysis or SRY-specific probes to identify SRY deletions and translocations) 26 27
          • Further specific testing for sex determination is complex in individuals with ambiguous genitalia and performed at centers with expertise in caring for children with disorders of sexual development; whole genome sequencing may be required 9
        • If infant does not have bilateral anorchia or congenital adrenal hyperplasia, examine under anesthesia or explore surgically to locate undescended testes or testicular remnants; 1 gonadectomy is performed on patients with abnormal SRY testing or gonadal dysgenesis with Y chromosome material owing to increased risk of gonadoblastoma in these patients 28
    • Older child with bilateral cryptorchidism 1
      • Evaluate for bilateral nonpalpable undescended testes and bilateral anorchia
        • Obtain serum hormone levels (eg, testosterone, luteinizing hormone, follicle-stimulating hormone, inhibin B, and müllerian inhibiting substance) and consider hCG stimulation test to assess for testosterone production in consultation with an endocrinologist and urologist
        • Examine under anesthesia with possible surgical exploration if anorchia is excluded
  • Obtain selected imaging studies only in certain clinical scenarios; otherwise, radiographic imaging does not alter diagnosis or management 1 10
    • Regardless of radiographic findings, surgical exploration for undescended testis is standard of care
    • Scrotal and pelvic ultrasonography 13
      • Ultrasonography is noncontributory in routine use 1
      • Imaging is not recommended before referral to urology 1
      • The few clinical indications include:
        • Phenotypic male with bilateral nonpalpable testes
          • Assess for the presence of 1 or both testes
          • Assess for the presence of uterine structures
        • Patients who are difficult to examine (eg, overweight children) to assess for inguinal testes
          • Surgical approach is inguinal when extra-abdominal testis is identified; initial surgical approach is abdominal when extra-abdominal testis is not identified
    • MRI offers higher sensitivity and specificity compared with ultrasonography but requires sedation

Laboratory

  • Serum glucose and electrolyte levels 29
    • Constellation of laboratory abnormalities in untreated patients with congenital adrenal hyperplasia include:
      • Serum sodium typically drops below 125 mmol/L days to weeks after birth in salt wasting patients 29
      • Severe hyperkalemia (less than 6.5 mmol/L) in all patients from 11 days after birth 29
      • Hypoglycemia may be present
  • Serum hormone levels
    • Testosterone
      • Leydig cells physiologically respond to endogenous luteinizing hormone or exogenous hCG by producing testosterone 1
      • Absent or low testosterone is present in 23% of patients with bilateral cryptorchidism, specifically in patients with hypogonadotropic hypogonadism or anorchia 3
      • Order a free testosterone level; calculated free testosterone level is based on total testosterone level, albumin level, and sex hormone–binding globulin level 25
      • Perform test before 10 AM, if possible, because of the circadian rhythm of male hormone production 25
      • A second level is necessary to confirm any testosterone value outside the reference range, owing to physiologic variations when testosterone levels are low 25
    • 17-hydroxyprogesterone level 1
      • Elevated with classic congenital adrenal hyperplasia (ie, 21-hydroxylase deficiency)
      • Ideally measure at 48 hours of life for improved accuracy 9
    • Antimüllerian hormone and inhibin B 1
      • Marker of Sertoli cell function; Sertoli cells respond to endogenous follicle-stimulating hormone by producing müllerian inhibiting substance and inhibin B 1
      • Absence indicates anorchia
    • Luteinizing hormone and follicle-stimulating hormone
      • Low levels confirm the diagnosis of hypogonadotropic hypogonadism 25
      • Elevated levels along with absence of antimüllerian hormone and inhibin B indicate anorchia 1
  • Karyotype test 30
    • Interphasic fluorescence in situ hybridization is conducted with X- and Y-specific probes
    • A large number of interphasic nuclei are assessed by fluorescence in situ hybridization to evaluate the percentage of each clone accurately if a mosaic is detected or suspected
    • Results are interpreted in conjunction with other diagnostics (eg, hormone levels, imaging studies)
    • Mosaicism in the sex chromosomes is indicative of disorder of sexual development (eg, ovotesticular disorder, gonadal dysgenesis) or other genetic syndrome (eg, Turner syndrome, Klinefelter syndrome) 9
  • Array comparative genomic hybridization analysis 30
    • Specialized analysis of genome with higher sensitivity than standard karyotype testing 31
    • Oligonucleotide probes are used to detect submicroscopic deletions and duplications (less than 3 Mb) 32
    • Consider if standard karyotype is normal and chromosomal abnormality or mosaicism is still suspected, particularly in patients with increasingly severe ambiguous genitalia 33
    • Results are variable depending on the disorder of sexual development and require specialized interpretation 26
  • SRY gene testing
    • SRY (sex determining region of the Y chromosome) gene presence and location is an important factor in determining testicular development; presence of intact and functional SRY gene on the Y chromosome imparts normal testicular development 27
    • Obtain on most patients with complex presentation to determine SRY presence; presence of abnormal SRY (eg, SRY deletions, duplications, translocations) places patient with dysgenic gonads or Y chromosome mosaicism at increased risk for gonadoblastoma and aids in definitive diagnosis 34 28
    • SRY location and evidence of mutation can be determined by a combination of molecular fluorescence in situ hybridization and SRY-specific probe techniques

Imaging

  • Ultrasonography
    • Routine ultrasonography is not indicated before consultation with a pediatric urologist in the evaluation of boys with nonpalpable testis 1
    • Ultrasonography is helpful in planning initial surgical approach (either laparoscopic or inguinal) in obese patients when palpation under anesthesia is limited; 3 otherwise ultrasonography is inferior to physical examination to determine extra-abdominal location of testis 10
    • Ultrasonography is indicated in patients with ambiguous genitalia, with nonpalpable testis associated with phallic abnormalities (eg, micropenis, hypospadias), and with discordant genitalia and chromosome compliment to assess internal anatomy and position of gonads 5
    • Ultrasonography can potentially identify nonpalpable testes in the inguinal canal but not within the abdomen 35
    • Ultrasonography sensitivity to locate a nonpalpable testis is 45% and specificity is 78% 35
  • MRI
    • Routine MRI imaging is not indicated before consultation with a pediatric urologist in the evaluation of boys with nonpalpable testis
    • MRI is occasionally useful in locating occult ectopic testis
    • MRI images can identify nonpalpable intra-abdominal testes with higher sensitivity and specificity compared with ultrasonography but are not 100% sensitive compared with surgical exploration 35
    • MRI sensitivity to locate a nonpalpable testis is 90% and specificity is 79% 35
    • Diffusion-weighted MRI has greater sensitivity and specificity of 96% and 100%, respectively 35

Procedures

2-handed testicular palpation
General explanation
  • Used to maximize rate of testicular detection on physical examination; performed as follows: 3
    • Patient lies supine in a warm room, with legs abducted initially
      • Cross-legged or baseball catcher’s position may aid in relaxing the cremaster muscle in patients who are obese, are noncooperative, and/or have a hyperactive cremasteric reflex
    • Assess the size, location, and texture of the contralateral descended testis with warm hands
    • Start the examination of the undescended testis at the anterior superior iliac spine and sweep the groin in a lateral to medial direction with the nondominant hand
    • On locating the testis, hold with the dominant hand and continue to sweep the testis toward the scrotum with the other hand
    • Check for testicular mobility, size, consistency, and spermatic cord tension
    • Immobilize the testis in the scrotum for 60 seconds to fatigue the cremaster muscle then release the testis; if it stays in place for a short time but then retracts, it is a retractile testis
Indication
  • To locate testis that is difficult to palpate and distinguish a retractile from undescended testis
Interpretation of results
  • Testis can be palpated manually by an experienced examiner in approximately 84% of patients 3
  • If the testis remains in place for a short time and then retracts, it is a retractile testis
Laparoscopic exploration for undescended testis by abdominal approach
General explanation
  • Abdominal surgical approach is used when undescended testis is not palpable by examination under anesthesia
  • Used to explore and confirm location and viability of nonpalpable undescended testis
  • Test of choice to determine if nonpalpable undescended testis is intra-abdominal, intracanalicular, atrophic, dysgenic, ectopic, or absent 10
Indication
  • All children older than 6 months (corrected for gestational age) with nonpalpable undescended testes
Contraindications
  • Uncorrected bleeding diathesis 36
  • Prior abdominal surgery with scar tissue 36
  • Known bilateral anorchia 1
Complications
  • Bleeding or hematoma formation
  • Inadvertent injury to intra-abdominal organs (eg, vessels, bowel, bladder)
  • Pneumoperitoneum
  • Postoperative wound infection or incisional hernia
Interpretation of results
  • Laparoscopy allows identification of the aberrant location of the missing testis, if present 1
  • If testis is absent (ie, vas deferens and testicular vessels stop before entering internal inguinal ring, or blind-ending vas deferens and testicular vessels are encountered), then vanishing testis is diagnosed
  • If a viable testis is located in an intra-abdominal position, orchiopexy ensues
  • If vas deferens and testicular vessels are found to enter the internal inguinal ring, then surgical approach is modified to groin approach
Groin exploration for undescended testis by inguinal or scrotal surgical approach
General explanation
  • Inguinal or scrotal surgical approach is used when undescended testis is palpable
  • Inguinal and/or scrotal incisions are used to explore and confirm location and viability of palpable undescended testis
Indication
  • Palpable undescended testis
Contraindications
  • Uncorrected bleeding diathesis
  • Known bilateral anorchia
Complications
  • Bleeding or hematoma formation
  • Injury to adjacent nerves, vessels, bladder, or testicular structures (eg, vessels, vas deferens, spermatic cord)
Interpretation of results
  • If atrophic testis or testicular remnants are found without viable testis, these structures are removed
  • If viable testis is encountered, the structures are restored to normal scrotal position by orchiopexy

Differential Diagnosis

Most common

  • Differential diagnosis based on clinical presentation
    • Retractile testis 37
      • Testis that is pulled into an extrascrotal position by an exaggerated cremasteric reflex; can be manually replaced in stable, dependent scrotal position and remain there without tension at least temporarily 1
      • Retractile testes are at increased risk for secondary ascent (acquired cryptorchidism) 1
      • Differentiate undescended prescrotal testis from retractile testis by physical examination
        • An undescended prescrotal testis can occasionally be manually repositioned down into scrotum but will immediately rise to aberrant position upon release; other times the testis will “pop” under examiner’s hand
        • A retractile testis will remain in the normal scrotal position while the cremasteric reflex is fatigued (ie, holding testis in scrotal sac for at least 60 seconds 31
        • Other techniques to assist in facilitating accurate examination and differentiating retractile from undescended testis include repeated examinations, different examination positions (eg, squatting baseball catcher’s position, knee-chest or cross-legged positions), different examination maneuvers (eg, standing Valsalva), warm environment, warm compress applied to inguinal canal, patient distraction techniques, and use of lubricant on examiner’s hands 1
      • Occasionally examination under anesthesia by urologist is required to definitively differentiate retractile from undescended prescrotal testis
    • Vanishing testis (testicular regression syndrome) 38
      • Testis was present early in fetal development, but disappeared in utero secondary to intrauterine torsion or vascular accident; rarely bilateral
      • Similarly to cryptorchidism, presents with nonpalpable testis
      • Suspect on examination based on finding of compensatory hypertrophy (eg, hypertrophy of contralateral descended testis)
      • Differentiated from intra-abdominal testes at laparoscopy with the finding of a rudimentary, blind-ending spermatic cord (ie, remnants of testicular structure are identifiable but testicular tissue is absent)
    • Testicular agenesis (anorchia) 13
      • Rare congenital absence of functioning testicular tissue can present clinically as a phenotypic male (usually with micropenis or other phallic abnormalities) with bilateral empty scrotum; testicular agenesis can be unilateral
      • Similarly to cryptorchidism, presents with nonpalpable testis or testes
      • Differentiate based on hormone levels
        • Laboratory values consistent with a lack of testicular tissue include elevated luteinizing hormone and follicle-stimulating hormone levels, absent antimüllerian hormone and inhibin B, and negative hCG stimulation test results (after age 3 months) 3
      • Surgical exploration identifies unilateral testicular agenesis (ie, no testicular structure including testicular tissue, vessels, or vas deferens)
  • Differential based on life-threatening or other common congenital disease associated with cryptorchidism
    • Congenital adrenal hyperplasia
      • A group of autosomal recessive defects in adrenal steroid biosynthesis that result in excessive androgen production 5
        • 95% of cases are caused by a deficiency in 21-hydroxylase (classic type) and present with ambiguous genitalia in female newborns and shock in males around age 1 week
      • Genes responsible for the 3 types of congenital adrenal hyperplasia that present with ambiguous genitalia include: 5
        • CYP21 (6p21-23) in 21-hydroxylase deficiency
        • CYP11B1 (8q24) in 11β-hydroxylase deficiency
        • HSD3B2 (1p13.1) in 3β-hydroxysteroid dehydrogenase deficiency
      • Depending on specific enzymatic defect responsible for the type of congenital adrenal hyperplasia, a combination of glucocorticoid and mineralocorticoid (ie, aldosterone) deficiency results in hypovolemic shock with associated hyponatremia, hyperkalemia, and sometimes hypoglycemia in infancy
      • Classic congenital adrenal hyperplasia presents with an ambiguous male phenotype (eg, male phallus/ambiguous genitalia, bilateral nonpalpable testes) in a genotypic female newborn (eg, XX)
      • Diagnose classic congenital adrenal hyperplasia with 46,XX karyotype and elevated 17-hydroxyprogesterone level; obtain adrenocorticotropic hormone stimulation test if 17-hydroxyprogesterone level is inconclusive 5
      • Less common variants present with accumulation of steroid precursors 11-deoxycortisol in patients with 11β-hydroxylase deficiency and elevated 17-hydroxypregnenolone and dehydroepiandrosterone in patients with 3β-hydroxysteroid dehydrogenase deficiency 5
      • Definitive diagnosis is confirmed with genetic testing
    • Isolated hypogonadotropic hypogonadism 25
      • Congenital hypogonadotropic hypogonadism presents with micropenis and bilateral cryptorchidism in infancy and is caused by 2 broad categories of disease; two-thirds of infants are found to have Kallmann syndrome and the rest are idiopathic 25
      • Kallmann syndrome is associated with anosmia (ie, lack of smell); mutations in the region of the KAL1 gene (Xp22.32) are responsible for X-linked recessive disease; several other known mutations are linked to both the syndrome and normosmic hypogonadotropic hypogonadism
      • Idiopathic hypogonadotropic hypogonadism is caused by a failure of gonadotropin-releasing hormone neurons in the hypothalamus to differentiate or develop; smell sensation is normal in these patients
      • Hypogonadotropic hypogonadism is characterized by low testosterone level with low luteinizing hormone and follicle-stimulating hormone levels; confirm lack of pituitary gonadotropin production (ie, lack of rise in luteinizing hormone/follicle-stimulating hormone production) with a gonadotropin-releasing hormone stimulation test
      • Definitive diagnosis of exact cause of congenital hypogonadotropic hypogonadism involves use of cerebral MRI to assess for absence or abnormalities in the olfactory bulb (ie, Kallmann syndrome); molecular testing helps to support the diagnosis of isolated congenital hypogonadotropic hypogonadism, but not all genetic defects responsible for disease are known
      • Differentiate from congenital cryptorchidism by clinical presentation and laboratory findings
    • Ovotesticular disorder (true hermaphroditism) 32
      • Disorder of sexual development defined as the presence of ovarian and testicular tissue in the same individual; often associated with 46,XX karyotype but can be associated with X/Y or mosaic XX/XY karyotype 5
      • Presents with a wide range of phenotypic variations in the genitalia with a mixture of both female müllerian and male wolffian structures; most common presentations include ambiguous genitalia and severe hypospadias 5
      • Exact cause is unclear; often a translocation of the SRY gene to the X chromosome or another chromosome is associated with disease; additionally abnormalities in SOX9, SOX3, 9 and DMR1 genes 5 are associated with disease 5
      • Diagnosis is complex and often elusive; molecular detection of SRY gene abnormalities or sex determining DMR1 gene deletions help to define the clinical picture 32
      • Whole genome sequencing 27 or custom capture and sequencing kit to evaluate for the 35 known key coding sequences involved in sex determination may be required to further characterize specifics of the disorder 32
      • Diagnosis is complex, involving physical examination, surgical exploration, multiple hormonal evaluations, imaging studies, genetic studies (including karyotype), and gonadal histology; evaluation is best conducted by a team of specialists with experience in disorders of sexual development
    • Mixed gonadal dysgenesis or partial gonadal dysgenesis 28
      • A subset of disorders of sexual development characterized by incomplete or defective formation of the gonads (ovary or testis) caused by either structural or numerical anomalies of the sex chromosomes or mutations in the genes involved in the development of the gonad 28
      • Partial gonadal dysgenesis occurs in individuals with usually 46,XY karyotype presenting with variable degrees of sexual ambiguity with an otherwise nonsyndromic phenotype; dysgenetic testes or streak gonads may be present 39
      • Mixed gonadal dysgenesis occurs in association with sex chromosome abnormalities (eg, mosaicism with a 45,X cell line and 1 or more lineages with a normal or structurally abnormal Y chromosome) and presents with variable degrees of sexual ambiguity 9 39
        • Patients may show syndromic features associated with this disorder (eg, Turner phenotype, camptomelic dysplasia, Denys-Drash syndrome)
      • Mixed and partial gonadal dysgenesis are similar in that they both present with variable degrees of ambiguous genitalia, including unilateral cryptorchidism with hypospadias
      • Numerous molecular associations exist for gonadal dysgenesis and many are unknown (eg, SRY gene abnormalities; mutations in SOX9SOX3WT1NR5A1DAX1WNT4CBX2DMRT1GATA4, and SF132 40
      • Whole genome sequencing 27 or custom capture and sequencing kit to evaluate for the 35 known key coding sequences involved in sex determination may be required to further characterize specifics of the disorder 32
      • Diagnosis is complex, involving physical examination, surgical exploration, multiple hormonal evaluations, imaging studies, genetic studies (including karyotype), and gonadal histology; evaluation is best conducted by a team of specialists with experience in disorders of sexual development 28

Treatment

Goals

  • Restore viable testis to correct position
  • Remove nonviable testis and testicular remnants
  • Decrease risk of complications (eg, impaired spermatogenesis, testicular cancer, torsion)

Disposition

Admission criteria

Admit infants with bilateral cryptorchidism or phallic abnormalities for further evaluation and treatment

Criteria for ICU admission
  • Admit infants with ambiguous genitalia to the neonatal ICU

Recommendations for specialist referral 1

  • Refer the following patients to a pediatric urologist:
    • Infants diagnosed with undescended testis who do not have spontaneous testicular descent by age 6 months (corrected for gestational age)
    • Boys older than 6 months (corrected for gestational age) with newly diagnosed undescended testis
    • Patients in whom there is difficulty differentiating between retractile testis and undescended testis
    • Prompt consultation with urologist is indicated in any child with undescended testis who presents with severe abdominal or groin pain, owing to increased risk of hernia (incarcerated or strangulated) or torsion
  • Consult appropriate specialists (eg, multidisciplinary team with a pediatric endocrinologist and pediatric urologist) for evaluation of possible congenital adrenal hyperplasia and disorder of sexual development in: 1
    • All phenotypic male newborns with bilateral nonpalpable testes
    • All patients with unilateral nonpalpable testis with abnormal phallus (eg, hypospadias, micropenis) or otherwise ambiguous genitalia
  • Consult geneticist for any syndromic male with bilateral nonpalpable testes for further characterization of possible congenital syndrome
  • Failure to immediately refer patients with bilateral cryptorchidism to pediatric urologist and pediatric endocrinologist for appropriate evaluation and treatment can result in increased morbidity and mortality from missed diagnosis (eg, disorders of sexual development, congenital syndromes)
    • Infants with bilateral cryptorchidism or ambiguous genitalia require urgent evaluation for congenital adrenal hyperplasia with serum glucose/electrolyte measurement, karyotype analysis, and multidisciplinary team consult with pediatric urologist and pediatric endocrinologist
  • Avoid radiographic imaging before referral for expert examination or examination under anesthesia; imaging does not often contribute to management decisions

Treatment Options

An undescended testis requires surgical relocation by age 18 months (corrected for gestational age) 38 41

Orchiopexy of the undescended testis is the first line of treatment 42

  • Ideally perform surgery before age 18 months if testis does not descend spontaneously by age 6 months (corrected for gestational age) 1
  • Management of acquired undescended testis is not rigorously standardized and may vary depending on individual patient, location of testis, and recommendation of consultant pediatric urologist
    • Acquired undescended testis (with volume appropriate for age) before puberty is often repaired by orchiopexy at the time of diagnosis 43
    • Occasionally acquired undescended testis is managed with observation for spontaneous descent; spontaneous descent occurs in up to 77% of patients with acquired undescended testis during puberty 44

Postpubertal acquired cryptorchidism is carefully managed in consultation with a urologist 1

  • Management is individualized 45
    • Options include orchiectomy, orchiopexy, and observation without surgical intervention
  • Testis requires biopsy before orchiopexy
  • Decision to relocate testis into normal position depends on numerous factors including pathology results, status of contralateral testis, and associated medical conditions
  • Often requires orchidectomy 10

Children found to have congenital adrenal hyperplasia or other disorder of sexual development (eg, gonadal dysgenesis, hypogonadotropic hypogonadism, ovotesticular disorder) require individualized management depending on nature of underlying disorder

Educate family and patients with a history of undescended testis (cryptorchidism) of potential increased risk of testicular cancer and importance of self-examinations 46

Drug therapy

  • Hormonal therapy (eg, hCG, luteinizing hormone–releasing hormone, gonadotropin-releasing hormone) to induce spontaneous testicular descent is no longer recommended by the American Urological Association; the European Association of Urology/European Society for Paediatric Urology guidelines recommend not routinely offering hormonal therapy, in either adjuvant or neoadjuvant settings, for testicular descent—patients should be evaluated on an individual basis 1 41

Nondrug and supportive care

Procedures
Orchiopexy

General explanation

  • Open or laparoscopic surgery to reposition the testes within the scrotal sac and secure in normal position 1
  • Associated inguinal hernias are repaired
  • Identify the status of the testis and testicular vessels during surgical exploration to ascertain the course of action
    • Perform laparoscopic orchidectomy if testis has abnormal morphologic appearance or patient is postpubertal 1
    • Perform laparoscopic orchiopexy if testis is normal in appearance and testicular vessels are adequate length for procedure
    • Perform stage 1 of 2-stage Fowler-Stephens orchiopexy if testis is normal in appearance and testicular vessels are inadequate length for laparoscopically assisted repair; occasionally orchidectomy is required in patients with normal contralateral testis when vessels and vas deferens are very short 1

Indication

  • If the testes are present and do not descend spontaneously by age 6 months (corrected for gestational age), perform surgery within the next year 38 41
  • In prepubertal boys with palpable undescended testes, perform scrotal or inguinal orchiopexy 1
  • In prepubertal boys with nonpalpable undescended testes, examine under anesthesia to confirm nonpalpability; if confirmed, perform surgical exploration and orchiopexy 1

Contraindications

  • Uncorrected bleeding diathesis

Complications

  • Testicular retraction and atrophy in 0% to 2% 3
  • Postoperative hernia in 2% to 3% 3
  • Rarely injury to adjacent structures (eg, nerve, vessel, vas deferens)

Interpretation of results

  • Surgical success following orchiopexy (ie, testis remains in intrascrotal position without atrophy) depends on testicular position before surgical intervention; success rates vary from 74% to 95% 2 10

Comorbidities

  • Congenital adrenal hyperplasia
    • Immediate management for ill-appearing patients with congenital adrenal hyperplasia includes stress glucocorticoid replacement, volume replacement, and correction of glucose and electrolyte derangements 47
    • Patients with congenital adrenal hyperplasia require maintenance corticosteroid, mineralocorticoid, and electrolyte replacements depending on specific enzyme defect responsible for disease (eg, hydrocortisone, fludrocortisone, and sodium chloride supplementation) 5
  • Disorders of sexual development 5
    • Patients with disorders of sexual development (eg, gonadal dysgenesis, hypogonadotropic hypogonadism, ovotesticular disorder) require specialized management often based on assumed gender alignment

Monitoring

  • Serial electrolyte monitoring is indicated in any infants found to have congenital adrenal hyperplasia
  • Children with delayed initial descent of testis (ie, absence of testis in scrotum at birth with subsequent spontaneous descent by a few months of life) require yearly examinations during childhood to monitor for acquired cryptorchidism 10
  • Children with retractile testis require yearly examinations to document lack of secondary ascent (ie, acquired cryptorchidism) 1
  • Postoperative patients are monitored in the weeks to months following orchiopexy, usually by urology service at intervals determined by individual surgeons to assess for therapeutic failure and need for further intervention
  • Primary care physicians monitor postoperative patients following orchiopexy with yearly examinations and encourage monthly patient self-examinations owing to increased risk of testicular malignancy

Complications and Prognosis

Complications

  • Testicular cancer
    • Risk for testicular cancer is 2.5- to 8-fold higher in patients with an unrepaired undescended testis compared with the general population 3
      • Risk is greater overall for men with intra-abdominal or bilateral cryptorchidism 21
    • Orchiopexy does not eliminate the risk of cancer in a previously undescended testis; risk of cancer is diminished to 2- to 3-fold higher than the general population if prepubertal orchiopexy is performed 3
    • Earlier age at orchiopexy is associated with decreased relative risk of malignancy in the involved testis 38
    • Children with acquired cryptorchidism are at risk of developing testicular malignancy; degree of increased risk is not definitively known 1
    • Patients with ectopic and retractile testis are not at increased risk for malignancy
  • Infertility
    • Complete loss of germ cells is a risk if orchiopexy is not performed by age 18 months (corrected for gestational age) 38
    • Children with acquired bilateral cryptorchidism are at risk of developing diminished fertility 1
    • Formerly bilaterally cryptorchid men have an up to 6-fold increased risk of infertility 1
    • Unilaterally cryptorchid men have paternity rates similar to the general population 21
  • Inguinal hernia 48
    • Over 90% of patients with disease have an associated hernia requiring repair at the time of orchiopexy 48
  • Testicular torsion49
    • 10 times higher risk in patients with cryptorchidism; earlier age at orchiopexy decreases risk of torsion 49
  • Testicular and genital trauma
    • Risk of blunt trauma from compression against bony structures is increased if the location is in the inguinal canal

Prognosis

  • Most undescended testes will spontaneously descend by age 6 months (corrected for gestational age) 1 2
  • Overall prognosis is good barring the development of testicular cancer in patients with a history of cryptorchidism following orchiopexy
  • Prognosis for testicular salvage is good if the testis is positioned in correct location by orchiopexy before age 18 months (corrected for gestational age)
    • Success rate (ie, no testicular atrophy or recurrence of cryptorchidism) of orchiopexy for inguinal testes is up to 95% 2
    • Success rate of orchiopexy for patients with abdominal testes is slightly lower than for patients with lower preoperative descent of testis 2
  • Prognosis for testicular function
    • Infertility is more common in patients with uncorrected and bilateral cryptorchidism 1

Screening and Prevention

Screening

At-risk populations

  • Males 1

Screening tests

  • Palpate testes for quality and position at each well-child visit in the first year of life and subsequent annual physical examinations 1
    • Early diagnosis and treatment of undescended testis will prevent complications 1
    • Testicular position may change as the child grows (acquired cryptorchid testis)

Prevention

  • Pregnant women should avoid exposure to hormone-mimicking substances, especially estrogen and xenoestrogens 20

Sources

1: Kolon TF et al: Evaluation and treatment of cryptorchidism: AUA guideline. J Urol. 192(2):337-45, 2014

Cross Reference