Basics
Description
Cryptorchidism is a condition characterized by one or both testes being undescended. An undescended testis does not remain at the bottom of the scrotum after the cremaster muscle has been fatigued by overstretching. Cryptorchidism is commonly confused with a retractile testis. A retractile testis may not always lie in the scrotum but will stay at the bottom of the scrotum after overstretching the cremaster.
Epidemiology
- 3% of full-term newborn boys have cryptorchidism.
- This percentage falls to 1% by 3 months of age.
- There are 2 peaks for detection of undescended testes: at birth and at 5-7 years of age. The latter group probably represents those patients with low undescended testes that become apparent with linear growth.
- Bilateral undescended testes occur in 10% of patients with undescended testicles.
- Unilateral anorchia is found in 5% of patients with cryptorchidism.
Genetics
- Of boys with undescended testes, 4% of their fathers and 6-10% of their brothers also had undescended testes. There is a 23% prevalence of cryptorchidism in family members of cases compared to 7.5% of relatives of controls.
- Androgen receptor gene mutations are not linked to isolated cryptorchidism. Abnormalities in HOXA10, HOXA11, HOXD13, ESR1, INSL3, and the LGR8/GREAT receptor genes are being investigated in patients with cryptorchidism.
Pathophysiology
- Normal testicular descent occurs during the 7th month of gestation.
- The majority of testes that are undescended at birth but will descend spontaneously do so by 3 months of age, possibly due to the gonadotropin surge that is responsible for germ cell maturation.
- The undescended testis fails to show normal maturation at both 3 months and 5 years of age.
- At 3 months of age, the fetal gonocytes are transformed into adult dark spermatogonia.
- At 5 years of age, the adult dark spermatogonia become primary spermatocytes.
- Both of these steps are abnormal in the undescended testis and, to a lesser extent, the contralateral descended testis.
- Previous beliefs that the undescended testis was normal between birth and 1 year of age are incorrect because they were derived from counts of all germ cells without taking into account whether maturation was occurring.
- After 5 years of age, thermal effects on the testis left out of position are seen independent of the endocrinologic effects.
Etiology
- A multifactorial mechanism involving 2 theories have been postulated:
- Hypogonadotropic hypogonadism
- Abnormal mechanical factors (gubernaculum, epididymis, genitofemoral nerve innervation, intra-abdominal pressure)
- Although boys with undescended testes do have abnormal attachment of the gubernaculum, the mechanical theories do not consistently explain the testis histology found in cryptorchidism.
- Many boys with cryptorchidism have lower morning urinary luteinizing hormone and a decreased luteinizing hormone/follicle-stimulating hormone response to gonadotropin-releasing hormone, corresponding to the abnormal germ cell development in both the undescended and contralateral descended testis.
- The normal initial postnatal gonadotropin surge at 60-90 days of age is absent or blunted in some boys with cryptorchidism. Without this surge, Leydig cells do not proliferate, testosterone does not increase, germ cells do not mature, and infertility may develop. This indicates that a mild endocrinopathy is responsible, and cryptorchidism may be a variant of hypogonadotropic hypogonadism.
- Secondary undescended testes can occur after inguinal surgery, either due to scar tissue or difficulty in diagnosing an undescended testis in a young boy with a hernia.
Commonly Associated Conditions
- Patients with prune belly, Klinefelter, Noonan, and Prader-Willi syndromes have a higher likelihood of undescended testes.
- Cryptorchidism associated with hypospadias should also raise the possibility of a disorder of sex development (DSD), which occurs in 30-40% of patients, mainly consisting of defects in gonadotropin or testosterone synthesis.
Diagnosis
History
- Exogenous maternal hormones (used in infertility treatments)
- Maternal oral contraceptive use
- Consanguinity
- Family history of urologic abnormalities or neonatal deaths
- Prematurity
- CNS lesions
- Previous inguinal surgery
- Precocious puberty
- Infertility
Physical Exam
- The undescended testis may be found at the upper scrotum, in the superficial inguinal pouch, or in the inguinal canal. For treatment purposes, the main distinction that needs to be made is whether or not the testis is palpable.
- The patient should be examined sitting in the frog-leg position.
- With warmed hands, check the size, location, and texture of the contralateral descended testis.
- Begin the examination of the undescended testis at the anterior superior iliac spine.
- Sweep the groin from lateral to medial with the nondominant hand.
- Once the testis is palpated, grasp it with the dominant hand and continue to sweep the testis toward the scrotum with the other hand.
- With a combination of sweeping and pulling, it is sometimes possible to bring the testis to the scrotum.
- Maintain the position of the testis in the scrotum for a minute so that the cremaster muscle is fatigued.
- Release the testis, and if it remains in place, it is a retractile testis.
- If it immediately pops back, it is an undescended testis.
- For difficult-to-examine patients (chubby 6-month-olds or obese youth), having them sit with heels together and knees abducted can help relax the cremaster. Wetting the fingers of the nondominant hand with lubricating jelly or soap can increase the sensitivity of the fingers in palpating the small, mobile testis.
Diagnostic Tests & Interpretation
Lab
- For the typical patient with a unilateral palpable or nonpalpable undescended testis, no further laboratory evaluation is necessary.
- For the patient with bilateral undescended testis, with 1 testis palpable, no further workup is necessary.
- The patient with bilateral nonpalpable testes should have a chromosomal and endocrinologic evaluation, as should the patient with 1 or 2 undescended testes and hypospadias.
- If the patient has bilateral nonpalpable testes and is <3 months of age, serum luteinizing hormone, follicle-stimulating hormone, testosterone, and anti-m źllerian hormone levels will determine whether testes are present.
- After that age, human chorionic gonadotropin stimulation will result in a measurable serum testosterone if testes are present. A failure to respond to human chorionic gonadotropin stimulation in combination with elevated luteinizing hormone/follicle-stimulating hormone levels is consistent with anorchia.
Imaging
Ultrasound, CT, and MRI can detect testes in the inguinal region, but this is also the region where they are most easily palpable. They are only 50% accurate in showing intra-abdominal testes. Imaging is not necessary preoperatively because, for nonpalpable testes, surgical planning is based on the exam performed in the clinic and under anesthesia.
Differential Diagnosis
- Retractile testes are commonly confused with undescended testes. The key to distinguishing them from undescended testes is the physical exam.
- All retractile and many undescended testes can be delivered into the scrotum.
- The retractile testis will stay in the scrotum after the cremaster muscle has been overstretched.
- The low undescended testis will immediately pop back to its undescended position after being released.
- Atrophic or "vanishing" testes are found anywhere along the normal path to the scrotum.
- They are believed to be due to neonatal vascular ischemia.
- The contralateral testis can be hypertrophied in these boys, but this is not a reliable diagnostic sign.
- Anorchia or DSD
- On evaluation, 80% of nonpalpable testes are present in either the abdomen or in the inguinal canal.
- A child with bilateral nonpalpable testes should have an endocrine evaluation to rule out anorchia or DSD.
Treatment
Additional Treatment
General Measures
- Patients with undescended testes should be referred for surgical evaluation no later than 3 months of age.
- Hormonal therapy
- Hormonal therapy was widely used in Europe for inducing descent of undescended testes. Both gonadotropin-releasing hormone and human chorionic gonadotropin were used, with long-term success rates of 20%.
- Treatment is most successful for low undescended testes, but there is a 25% relapse rate.
- More recent recommendations from European pediatric endocrinologists indicate that surgery is the preferred therapy.
- For these reasons, as well as that gonadotropin-releasing hormone and human chorionic gonadotropin are not approved for this indication in the United States, most therapy in the United States to bring the testis down to the scrotum is surgical (orchiopexy).
- The use of hormonal therapy after orchiopexy to improve semen analyses in high-risk patients is in its preliminary stages of investigation in Europe and the United States.
Surgery/Other Procedures
Goals in bringing the testis into the scrotum:
- Prevent ongoing thermal damage to the testis.
- Treat the associated hernia sac.
- Prevent testis torsion/injury against the pubic bone.
- Achieve a good cosmetic result/avoid psychological effects of empty scrotum.
- Allow the older child to perform testicular self-exam for cancer.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
After successful orchiopexy, patients are examined at 6-12 months to check on testicular size and position. They are rechecked at puberty to explain the technique and need for monthly testis self-exam concerning early recognition of testis cancer. Patients with retractile testes should be examined annually until age 7 years because ~5% will be found to have a testis out of the scrotum.
Prognosis
- Surgery cannot reverse the maturational failure of the undescended testis, but it can prevent ongoing thermal injury.
- Parents are often concerned about future fertility:
- In patients who have undergone orchiopexy at an early age, it appears that 90% of boys with unilateral cryptorchidism and 65% with bilateral cryptorchidism will achieve paternity.
- Patients who are interested in their risk for infertility may have a semen analysis performed at age 18 years.
- Surgery decreases the relative risk of testicular cancer if the surgery is performed before 13 years of age.
- All patients should be taught proper monthly testicular self-exam at the time of puberty. Some patients with cryptorchidism are at a higher risk of cancer (prune belly syndrome, ambiguous genitalia, karyotypic abnormalities, or the postpubertal boy).
Additional Reading
- Callaghan P. Undescended testis. Pediatr Rev. 2000;21(11):395. [View Abstract]
- Lee PA. Fertility after cryptorchidism: epidemiology and other outcome studies. Urology. 2005;66(2):427-431. [View Abstract]
- Pettersson A, Richiardi L, Nordenskjold A, et al. Age at surgery for undescended testis and risk for testicular cancer. N Engl J Med. 2007;356(18):1835-1841. [View Abstract]
- Pyorala S, Huttunen NP, Uhari M. A review and meta-analysis of hormonal treatment of cryptorchidism. J Clin Endocrinol Metab. 1995;80(9):2795-2799. [View Abstract]
- Ritzen EM. Undescended testes: a consensus on management. Eur J Endocrinol. 2008;159(Suppl 1):S87-S90. [View Abstract]
- Tasian GE, Yiee JH, Copp HL. Imaging use and cryptorchidism: determinants of practice patterns. J Urol. 2011;185(5):1882-1887. [View Abstract]
- Virtanen HE, Bjerknes R, Cortes D, et al. Cryptorchidism: classification, prevalence and long-term consequences. Acta Paediatr. 2007;96(5):611-616. [View Abstract]
- Virtanen HE, Cortes D, Rajpert-De Meyts E, et al. Development and descent of the testis in relation to cryptorchidism. Acta Paediatr. 2007;96(5):622-627. [View Abstract]
Codes
ICD09
- 752.51 Undescended testis
ICD10
- Q53.9 Undescended testicle, unspecified
- Q53.10 Unspecified undescended testicle, unilateral
- Q53.20 Undescended testicle, unspecified, bilateral
- Q53.11 Abdominal testis, unilateral
- Q53.12 Ectopic perineal testis, unilateral
- Q53.21 Abdominal testis, bilateral
- Q53.22 Ectopic perineal testis, bilateral
SNOMED
- 204878001 Undescended testicle (disorder)
- 268228006 Undescended testes - bilateral
- 4.3178100012e+014 Bilateral intra-abdominal testes (disorder)
FAQ
- Q: If there is only 1 testicle in the scrotum, will fertility be affected?
- A: In general, the outlook for paternity is good in a patient with only 1 descended testicle. Paternity is more significantly affected with a history of 2 undescended testicles.
- Q: Why do patients with retractile testes require follow-up?
- A: The ability to distinguish between retractile and undescended testes can be difficult in some patients. Some of the patients will be found to have true undescended testes as they grow. Boys should be taught how to perform a monthly testicular self-exam at puberty.