Cryptorchidism: Symptoms, Causes, Mechanism, Pathophysiology, Diagnosis and Treatment

It refers to the absence of one or both testes of the scrotum.

The word is from the Greek κρυπτός, kryptos, which means hidden ὄρχις, orchis, which means testicle. It is the most common birth defect of the male genitalia.

Approximately 3% of full-term babies and 30% of premature babies are born with at least one undescended testicle.

However, about 80% of the cryptorchid testicles descend in the first year of life (most in three months), which makes the actual incidence of cryptorchidism about 1% in general.

Cryptorchidism can develop after childhood, sometimes until early adulthood, but that is exceptional.

It is different from monorquismo, the condition of having only one testicle. The condition can occur on one or both sides; It is more common to affect the right testicle.

A testicle absent from the normal scrotal position may be:

  • Anywhere along the “descent path” from high in the posterior abdomen (retroperitoneal), just below the kidney, to the inguinal ring.
  • In the inguinal canal.
  • Ectopic, having “wandered” from the path of descent, usually outside the inguinal canal and sometimes even below the skin of the thigh, the perineum, the opposite scrotum, or the femoral canal.
  • Underdeveloped (hypoplastic) or severely abnormal (dysgenetic).
  • Missing

About two-thirds of the cases without other abnormalities are unilateral, most of the other third involve both testicles.

In 90% of cases, you can feel an undescended testicle in the inguinal canal. In a small minority of cases, the missing testicles can be found in the abdomen or appear to be non-existent (actually “hidden”).

Undescended testes are associated with reduced fertility, increased risk of germ cell testicular tumors, and psychological problems as the child grows.

Undescended testes are also more susceptible to testicular torsion (and subsequent infarction) and inguinal hernias.

Without intervention, an undescended testicle will usually descend during the first year of life, but to reduce these risks, undescended testes can enter the scrotum in childhood through a surgical procedure called orchiopexy .

Although cryptorchidism almost always refers to congenital or maldescent absence, a testicle observed in the scrotum in early childhood may occasionally “re-ascend” (recede) into the inguinal canal. A testicle that can move or move easily between the scrotum and the duct is known as retractable.

Cryptorchidism, hypospadias, testicular cancer and poor semen quality make up the syndrome known as testicular dysgenesis syndrome.

Signs and symptoms

Sterility:

Many men who were born with undescended testes have reduced fertility, even after orchiopexy in childhood.

The reduction with unilateral cryptorchidism is subtle, with an informed infertility rate of approximately 10%, compared to approximately 6% reported by the same study for the general population of adult men.

The reduction of fertility after orchiopexy for bilateral cryptorchidism is more marked, around 38%, or 6 times that of the general population.

The basis of the universal recommendation for early surgery is the research that shows the degeneration of the spermatogenic tissue and the reduction of the spermatogonial count after the second year of life in the undescended testes.

The degree to which this is prevented or improved by early orchiopexy is still uncertain.

Cancer risk:

One of the strongest arguments for early orchiopexy is the reduction of the risk of testicular cancer.

Approximately 1 in 500 men born with one or both undescended testicles develops testicular cancer, approximately an increase of 4 to 40 times the risk. The maximum incidence occurs in the third and fourth decades of life.

The risk is higher for the intra-abdominal testes and somewhat lower for the inguinal testes, but even the testicles normally descended from a man whose other testicle did not descend have a 20% higher risk of cancer than those of other men.

The most common type of testicular cancer that occurs in undescended testes is seminoma.

It can usually be treated if it is detected early, so urologists often recommend that children who had orchiopexy as babies be taught testicular self-examination, that they recognize testicular masses and seek early medical attention for them.

It is unlikely that cancer that develops in an intra-abdominal testicle before considerable growth and spread is recognized, and one of the advantages of orchidopexy is that a developing mass in a scrotal testicle is much easier to recognize than a mass intraabdominal

Initially, it was thought that orchidopexy made it easier to detect testicular cancer, but it did not reduce the risk of developing cancer. However, recent data has resulted in a paradigm shift.

The New England Journal of Medicine published in 2007 that orchidopexy performed before puberty resulted in a significantly lower risk of testicular cancer than if it were done after puberty.

The risk of malignancy in the undescended testicle is 4 to 10 times higher than in the general population and is approximately 1 in 80 with a unilateral undescended testicle and 1 in 40 to 1 in 50 for the undescended soft testicles.

The maximum age for this tumor is 15-45 years. The most common tumor that develops in an undescended testicle is a seminoma (65%); in contrast, after orchiopexy, seminomas represent only 30% of testicular tumors.

Psychological consequences:

There is a small body of research on the psychology of cryptorchidism, which tries to determine if this condition can cause lasting psychological problems.

Psychological research on cryptorchidism consists of only a few case reports and small studies.

This research also has serious methodological problems: the main variables are completely uncontrolled, such as the small physical stature of many cryptorchid children and the psychological effects of corrective surgery.

Existing research indicates that children with undescended testes do not tend to be disordered by gender, effeminate or pre-homosexual. A disturbed self-image is formed only when family dynamics are destructive to the development of male self-esteem.

Such pathogenic attitudes were found in parents who focused on the child’s genital defect as a sign of their presumed effeminacy. However, when cryptorchism is surgically corrected, healthy masculinity becomes possible.

The basic sexual normality of these children was confirmed in a small retrospective study that evaluated male adolescents several years after their condition was surgically repaired.

They had become pretty well adjusted adolescents without special sexual or gender problems, and without distinctive features of psychopathological relevance.

Causes

In most term newborns with cryptorchidism but no other genital anomalies, no cause can be found, so this is a common, sporadic, unexplained (idiopathic) birth defect.

A combination of genetics, maternal health and other environmental factors can alter hormones and physical changes that influence the development of the testicles.

  • Very premature babies can be born before the descent of the testicles. Low birth weight is also a known factor.
  • A contributing role of environmental chemicals called endocrine disruptors that interfere with normal fetal hormonal balance has been proposed. The Mayo Cliniclists “parent exposure to some pesticides” as a known risk factor.
  • Diabetes and obesity in the mother.
  • Risk factors may include exposure to regular alcohol consumption during pregnancy (5 or more drinks per week, associated with a 3-fold increase in cryptorchidism, compared to mothers who do not drink.) Cigarette smoking is also a factor known risk).
  • Family history of undescended testicle or other problems of genital development.
  • Cryptorchidism occurs at a much higher rate in a large number of congenital malformation syndromes. Among the most common are the Down syndrome, Prader-Willi syndrome and Noonan syndrome .
  • In vitro fertilization, the use of cosmetics by the mother and preeclampsia have also been recognized as risk factors for the development of cryptorchidism.

In 2008, a study was published that investigated the possible relationship between cryptorchidism and prenatal exposure to a chemical called phthalate (DEHP) that is used in the manufacture of plastics.

The researchers found a significant association between the highest levels of DEHP metabolites in pregnant mothers and several sex-related changes, including incomplete lowering of the testicles in their offspring.

According to the study’s lead author, a national survey found that 25% of American women had phthalate levels similar to levels found to be associated with sexual abnormalities.

A 2010 study published in the European medical journal Human Reproductionexamined the prevalence of congenital cryptorchidism among offspring whose mothers had taken mild analgesics, mainly over-the-counter pain relievers that included ibuprofen (for example, Advil) and paracetamol (acetaminophen).

Combining the results of a survey of pregnant women before their due date correlated with the health of their children and an ex vivo rat model, the study found that pregnant women who had been exposed to mild analgesics had a higher prevalence of babies born with congenital cryptorchidism.

The concept of a masculine programming window (MPW for its acronym in English) derived from animal studies has posed the hypothesis of a new perception of the mechanism of testicular descent.

According to this concept, the state of testicular descent is “established” during the period of 8 to 14 weeks of gestation in humans. Undescended testes are the result of an alteration in androgen levels only during this programming window.

Mechanism

Normal development:

The testes begin as a migration of primordial germ cells into testicular cords along the gonadal crest in the abdomen of the early embryo.

The interaction of several male genes organizes this developing gonad into a testicle instead of an ovary in the second month of gestation.

During the 3rd to 5th month, the cells in the testes differentiate into testosterone-producing Leydig cells and Sertoli cells that produce anti-Müllerian hormone.

The germ cells in this environment become fetal spermatogonia. Male external genitalia develop during the third and fourth month of gestation and the fetus continues to grow, develop and differentiate.

The testes remain high in the abdomen until the 7th month of gestation, when they move from the abdomen through the inguinal channels to the two sides of the scrotum.

It has been proposed that movement occurs in two phases, under the control of somewhat different factors. The first phase, the movement through the abdomen to the entrance of the inguinal canal, seems controlled (or at least heavily influenced) by the anti-Müllerian hormone (AMH).

The second phase, in which the testicles move through the inguinal canal to the scrotum, depends on androgens (the most important thing is testosterone ).

In rodents, androgens induce the genitofemoral nerve to release peptide related to the calcitonin gene (CGRP), which produces rhythmic contractions of gubernaculum, a ligament that connects the testicle to the scrotum, but a similar mechanism in humans has not been demonstrated.

The bad development of gubernaculum, or the deficiency or insensitivity to the anti-Müllerian hormone or to the androgen can, therefore, prevent the testes from descending into the scrotum.

Some evidence suggests that there may even be an additional paracrine hormone, known as adenine, secreted by the testes.

In many babies with inguinal testes, the additional descent of the testes in the scrotum occurs in the first 6 months of life. This is attributed to the postnatal increase in gonadotropins and testosterone that normally occurs between the first and fourth months of life.

Spermatogenesis continues after birth. Between 3 and 5 months of age, some of the fetal spermatogonia residing along the basement membrane become type A spermatogonia.

More gradually, other fetal spermatogonia become B-type spermatogonia and primary spermatocytes in the fifth year after birth. Spermatogenesis stops at this stage until puberty.

Most of the undescended testicles of normal appearance are also normal by microscopic examination, but reduced spermatogonia can be found.

The tissue in the undescended testes becomes more markedly abnormal (“degenerates”) in microscopic appearance between 2 and 4 years after birth. There is some evidence that early orchidopexy reduces this degeneration.

Pathophysiology

At least one contributory mechanism for reduced spermatogenesis in the testis cryptorchidism is temperature.

The temperature of the testicles in the scrotum is at least a couple of degrees cooler than in the abdomen.

Experiments with animals in the mid-twentieth century suggested that raising the temperature could damage fertility.

Some circumstantial evidence suggests that tight underwear and other practices that raise testicular temperature for prolonged periods may be associated with a lower sperm count.

However, research in recent decades suggests that the question of fertility is more complex than a simple matter of temperature.

It seems likely that the subtle or transient deficiencies of the hormone or other factors that lead to the lack of descent also impair the development of spermatogenic tissue.

The inhibition of spermatogenesis by the common intra-abdominal temperature is so strong that the continuous suspension of normal testes has been investigated tightly against the inguinal ring in the upper part of the scrotum by means of special “suspensory reports” as a method of male contraception.

An additional factor that contributes to infertility is the high rate of abnormalities of the epididymis in children with cryptorchidism (more than 90% in some studies). Even after orchidopexy, these can also affect the maturation and motility of sperm at a later age.

Diagnosis

The most common diagnostic dilemma in children who would otherwise be normal is to distinguish a retractable testicle from a testicle that will not descend spontaneously into the scrotum.

The retractable testes are more common than the truly undescended testes and do not need to be operated on. In normal men, as the cremaster muscle relaxes or contracts, the testicle moves lower or higher (“retracts”) in the scrotum.

This cremetic reflex is much more active in young children than in older men. A retractable testicle high in the scrotum may be difficult to distinguish from a position in the inferior inguinal canal.

Although there are several maneuvers to do this, such as using a cross-legged position, soaping the examiner’s fingers or examining in a warm bath, the benefit of surgery in these cases may be a matter of clinical judgment.

In the minority of cases with bilaterally palpable testicles, it is often useful to perform more tests to locate the testicles, evaluate their function, and exclude additional problems.

Scrotal ultrasound or magnetic resonance imaging performed and interpreted by a radiologist often, although not invariably, locates the testicles while confirming the absence of a uterus.

On ultrasound, the undescended testicle usually looks small, less echogenic than the normal contralateral testicle and is usually located in the inguinal region. With color Doppler ultrasound, the vascularization of the undescended testicle is poor.

A karyotype can confirm or exclude forms of primary dysgenetic hypogonadism, such as Klinefelter syndrome or mixed gonadal dysgenesis.

Hormone levels (especially gonadotropins and antimullerian hormone) can help confirm that there are hormonally functional testes that are worth trying to rescue, as well as stimulation with a few injections of human chorionic gonadotropin to cause an increase in testosterone level .

Occasionally, these tests reveal an unsuspected and more complicated intersexual condition.

In the even smaller minority of cryptorchid infants who have other obvious birth defects of the genitals, the additional tests are crucial and have a high probability of detecting an intersexual condition or other anatomical anomalies.

Ambiguity may indicate an altered androgen synthesis or reduced sensitivity.

The presence of a uterus by pelvic ultrasound suggests a persistent Müllerian duct syndrome (deficiency or insensitivity of the anti-Müllerian hormone) or a severely virilized genetic woman with congenital adrenal hyperplasia.

An unequivocal micro-weight, especially accompanied by hypoglycaemia or jaundice , suggests congenital hypopituitarism.

Treatment

The primary management of cryptorchidism is watchful waiting, due to the high probability of self-resolution. When this fails, a surgery, called orchiopexy, is effective if the inguinal testes have not descended after 4 to 6 months.

The surgery is often performed by a pediatric urologist or a pediatric surgeon, but in many communities it is still a general urologist or a surgeon.

When the undescended testicle is in the inguinal canal, hormone therapy is sometimes attempted and sometimes successful. The most commonly used hormone therapy is human chorionic gonadotropin (HCG).

A series of human chorionic gonadotropin injections are given (10 injections for 5 weeks) and the testes / testes are re-evaluated at the end.

Although many trials have been published, the success rates reported vary widely, from approximately 5 to 50%, which probably reflects the various criteria for distinguishing the retractable testicles from the low inguinal testes.

Hormone treatment occasionally has incidental benefits of allowing confirmation of the responsiveness of Leydig cells (demonstrated by an increase in testosterone at the end of injections) or inducing the further growth of a small penis (through the increase in testosterone).

Some surgeons have reported on the facilitation of surgery, perhaps by improving the size, vascularization or tissue healing.

A newer hormonal intervention used in Europe is the use of gonadotropin-releasing hormone analogues, such as nafarelin or buserelin; Success rates and putative mechanism of action are similar to human chorionic gonadotropin.

Limited evidence suggests that the germ cell count is slightly better after hormonal treatment, this translates into a better sperm count and fertility rates at maturity has not been established.

The cost of any type of hormonal treatment is lower than that of surgery and the possibility of complications at the appropriate doses is minimal.

However, despite the potential benefits of a hormone therapy trial, many surgeons do not consider success rates high enough to be worthwhile, since the surgery itself is generally simple and uncomplicated.

In cases where the testicles are identified preoperatively in the inguinal canal, orchiopexy is often performed on an outpatient basis and has a very low complication rate. An incision is made on the inguinal canal.

The testicles with the structure of the cord and the blood supply that accompanies them are exposed, partially separated from the surrounding tissues (“mobilized”) and taken to the scrotum. It is sutured to the scrotal tissue or it is enclosed in a “bag of subdates”.

The associated passage back to the inguinal canal, an inguinal hernia , closes to prevent re-ascent. In patients with intra-abdominal malverse testicles, laparoscopy is useful to see for itself the pelvic structures, the position of the testicle and decide on surgery (single or step procedure).

Surgery becomes more complicated if the blood supply is not wide and elastic enough to stretch in the scrotum. In these cases, the supply can be divided, some boats are sacrificed with the expectation of an adequate collateral circulation.

In the worst case, the testicle must be “autotransplanted” in the scrotum, with all blood vessels connected by cutting and reconnecting (“anastomosed”).

When the testicle is in the abdomen, the first stage of the surgery is the exploration to locate it, evaluate its viability and determine the safest way to maintain or establish the blood supply.

Multistage surgeries, or autotransplantation and anastomosis, are most often necessary in these situations. With the same frequency, the intraabdominal exploration discovers that the testicle does not exist (“disappeared”) or is dysplastic and can not be rescued.

The main major complication of all types of orchidopexy is the loss of blood supply to the testicle, which results in loss of the testicle due to ischemic atrophy or fibrosis.

Cryptorchidism in other animals

Cryptorchidism is seen in all domestic animals, most commonly in stallions, boars and canines. The prevalence of this condition can vary according to the species and the breed.

Evidence of this condition is more likely in companion animals and pigs than in ruminants. The cause of this condition can vary from a combination of genetics, environment and epigenetics.

Dogs:

Cryptorchidism is common in male dogs, occurring at a rate of up to 10%. This condition is one of the most common congenital defects in purebred dogs (1-11%), with 14% reported in Siberian Eskimo dogs.

Although genetics is not fully understood, it is believed to be a recessive trait, and probably polygenetic. Some have speculated that it is an autosomal recessive trait limited by sex; however, it is unlikely to be simple recessive.

The canine testicles usually descend at ten days of age and are considered cryptorchid if they do not descend at the age of eight weeks. Cryptorchidism can be bilateral (causing infertility) or unilateral, and inguinal or abdominal (or both).

Because it is an inherited trait, affected dogs should not be reared and must be neutered. Parents should consider themselves carriers of the defect and a breeder should consider carefully whether or not to raise the carrier’s father.

Castration of non-descended pets should be considered for dogs with cryptorchidism due to the high rate of testicular cancer, especially sertoli cell tumors.

The incidence of testicular cancer is 13.6 times higher in dogs with testicles retained in the abdomen than in normal dogs.

Testicular torsion is also more likely in retained testes. Surgical correction is by palpation of the retained testicle and subsequent exploration of the inguinal canal or abdomen, however, it is contrary to the rules of the American Kennel Club to show the altered dogs, which makes this correction meaningless for the stock player.

The surgical correction is called orchidopexy, that is, a surgery to move a testicle not descended to the scrotum and fix it permanently there. Surgical correction is an option for dogs that will not be used for breeding.

The races commonly affected include:

  • Alaskan klee kai.
  • Boxer.
  • Chihuahua.
  • Dachshund (miniature).
  • Bulldog.
  • Maltese.
  • Schnauzer miniatura.
  • Pekinés.
  • Pomeranio.
  • Poodle.
  • Shetland sheepdog.
  • Husky siberiano.
  • Lebrel.
  • Yorkshire terrier.

Gatos:

Cryptorchidism is rarer in cats than in dogs. In one study, 1.9% of intact male cats had cryptorchidism.

The Persians are predisposed. Normally the testicles are in the scrotum at the age of six to eight weeks. Male cats with a testicle with cryptorchidism can be fertile; however, male cats with two testicles of cryptorchidism are more likely to be sterile.

Fumigation with urine is an indication that a cat without observable testicles can not be castrated, other signs are the presence of enlarged jowls, facial and thickened neck skin and spines on the penis (which usually recede within six weeks after castration).

Most cryptorchid cats have an inguinal testicle. Testicular tumors and testicular torsion are rare in cats with cryptorchidism, but castration is usually performed due to unwanted behavior, such as spraying urine.

Horses:

In horses, cryptorchidism is common enough for affected males to be castrated routinely.

Rarely, cryptorchidism is due to the presence of a congenital testicular tumor, such as a teratoma, which tends to grow.