cryptorchidism

Cryptorchidism is a condition where one or both testicles are not lowered into the scrotum. Cryptorchidism is often the cause of hormonal and reproductive dysfunction of the testicles. With normal physiological development, they should be in the scrotum at birth or by the end of the first year of life. This is a necessary condition for their normal functioning.

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Epidemiology

Cryptorchidism is a common form of sexual development disorder in childhood. According to literature, it occurs in 2-4% of newborns and 15-30% of premature babies at birth. With age, its frequency decreases and in children under 14 years old it is from 0.3 to 3%. According to Shakhbazyan, right-sided cryptorchidism occurs in 50.8%, left-sided cryptorchidism in 35.3%, and bilateral cryptorchidism in 13.9% of patients.

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Causes cryptorchidism

Factors causing cryptorchidism can be divided into 3 groups.

1. Mechanical factors: narrowness of the inguinal canal, underdevelopment of the vaginal process of the peritoneum and scrotum, shortening and underdevelopment of the spermatic cord and its vessels, absence of the guiding ligament and its intra-abdominal adhesions, hypoplasia of the spermatic artery, insufficient blood supply to the testicles, hernia.
2. Hormonal deficiency, depending on many reasons. Violation of the process of testicular descent depends on insufficient stimulation of Leydig cells by maternal chorionic gonadotropin. Changes in the gonadotropic function of the hypothalamic-pituitary system lead to a deficiency of differentiating hormones and gonadal dysgenesis. Later, during the period of postnatal development, dysplastic-dystrophic phenomena in the undescended testicle progress. Additional factors in this case are violation of the temperature regime and perversion of enzymatic processes in the testicular tissue. Constant traumatization leads to accumulation of antibodies in the blood and development of autoaggression. Autoimmune conflict aggravates the damage to the parenchyma of the testicles.
3. Endogenous disorders of testicular development, decreased sensitivity to hormones. The process of testicular descent depends not only on stimulation, but also on the sensitivity of embryonic Leydig cells to maternal gonadotropin, as, for example, in the syndrome of incomplete masculinization, or on insufficient sensitivity of target organs to androgens (in the syndrome of testicular feminization), as well as on the state of other receptive organs (guide ligament, vas deferens, etc.).

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Pathogenesis

It has been experimentally proven that the descent of the testicles into the scrotum is regulated by hormones: maternal chorionic gonadotropin stimulates the secretion of androgens in the embryonic testicles, and androgens secreted by embryonic Leydig cells cause the growth of the vas deferens and seminiferous tubules of the epididymis, testicle and guiding ligament. Thus, the entire normal process of formation and descent of the testicles into the scrotum, starting from the correct laying of the sex, is determined by the set of chromosomes, hormones of the fetal sex glands, maternal chorionic gonadotropin and luteinizing hormone of the fetus. The entire process is completed in the period from 6 months of intrauterine life to the 6th week of postnatal life.

As clinical experience accumulates, more and more data appear indicating the possibility of a combination of various diseases with cryptorchidism. Currently, more than 36 syndromes (such as Kallman syndrome) and diseases accompanied by cryptorchidism are known. Only in cases where it (or ectopia of the testicles) is the only developmental defect, is the diagnosis of cryptorchidism as an independent disease valid.

Numerous reports that have appeared in recent years indicate that the disease is characterized not only by an abnormal position of the testicles, but is also expressed in significant disturbances in the function of the pituitary-gonadal complex.

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Symptoms cryptorchidism

Cryptorchidism is divided into congenital and acquired, unilateral and bilateral; by the location of the testicles - into abdominal and inguinal forms. True cryptorchidism is always accompanied by underdevelopment of one half or the entire scrotum. This symptom was described in 1937 by Hamilton. The testicle gets stuck on the way down and can be located in the abdominal cavity (abdominal cryptorchidism) or, which is more common, in the inguinal canal (inguinal cryptorchidism). Monorchism and anorchism occur in 1-3% of all those suffering from cryptorchidism.

In unilateral cryptorchidism, the reproductive and hormonal functions are performed by one testicle, which is lowered into the scrotum.

The inguinal form of true cryptorchidism should be distinguished from pseudocryptorchidism (migrating testicle), in which a normally descended testicle may periodically be outside the scrotum under the influence of a strong contraction of the muscle that lifts it (strong cremasteric reflex). When palpated, such a testicle is easily lowered into the scrotum. A condition close to cryptorchidism is ectopia of the testicle. If its incomplete migration leads to cryptorchidism, then deviation from the path of descent leads to ectopia, i.e. its unusual location. Having passed through the inguinal canal, the testicle does not descend into the scrotum, but is located under the skin in one of the adjacent areas.

This pathology is facilitated by congenital defects of the guiding ligament. A distinction is made between prefascial (testis refluxus) and superficial inguinal ectopia. In this case, the cord has a normal length, but the testicle is displaced to the area in front of the inguinal canal. Differential diagnostics of cryptorchidism from ectopia is important when choosing treatment tactics. If hormonal treatment is used for the first, then only surgical treatment is required for the second. Often, without surgical release of the testicle, it is impossible to diagnose and distinguish ectopia from true cryptorchidism. Intermediate, femoral and crossed ectopia are rare. It is also uncommon for both testicles to be located in one half of the scrotum.

In both congenital and experimental cryptorchidism, results were obtained indicating that in dystopic testicles, degeneration processes of the spermatogenic epithelium occur with a decrease in the diameter of the tubules, the number of spermatogonia, and the mass of the testicle. Changes were observed in all cells of the spermatogenetic series. The greatest defects were in germ cells at higher stages of differentiation. Using histomorphometric analysis, it was possible to prove that with cryptorchidism, no developmental disorders in the testicles occur until the end of the 2nd year of the child's life. However, from this point on, a clear change in the number of spermatogonia can be noted, as well as a narrowing of the seminiferous tubules compared to normal sizes. Thus, with cryptorchidism and ectopia, testicular damage appears after 2 years of the child's life.

Normal spermatogenesis occurs only at a certain temperature, which in men in the scrotum is 1.5-2 °C lower than body temperature. The germinal epithelium is very sensitive to it. An increase in the temperature of the testicles can lead to the cessation of spermatogenesis and infertility. Their displacement to the abdomen or inguinal canal, hot baths, febrile diseases or very high ambient temperatures can cause degenerative changes in the germinal epithelium in men. Maintenance of the optimal temperature of the testicles is guaranteed only by their placement in the scrotum, which performs a thermoregulatory function. The degree of degenerative changes in the germinal epithelium increases with the duration of overheating.

In accordance with the above, it was proposed to begin treatment of cryptorchidism before the end of the 2nd year of life. A good prognosis was noted even in cases where cryptorchidism exists until the 7th year of life. The mechanisms leading to a reduction or disappearance of the ability of the germinal epithelium to reproduce are still unclear. There is an assumption that, along with the harmful effect of overheating on the mitotic ability of spermatogonia to divide in the testicles in cryptorchidism, autoimmunological processes lead to degenerative damage to the epithelium.

The studies of A. Attanasio et al. were devoted to the study of disorders of hormonal regulation of spermatogenesis. The hormonal function of the testicles in the prepubertal period under the influence of hCG (human chorionic gonadotropin) was studied. The secretion of T in normal testicles and in cryptorchidism was compared. The possibility of stimulating T secretion by testicles in cryptorchidism under the influence of hCG was revealed. Normal endocrine function of the testicles is a condition for their normal descent. When the pathology was eliminated by treatment with hCG, the testicles had a better fertilizing capacity compared to testicles whose cryptorchidism was eliminated surgically. To date, it has not been definitively determined how long the abnormal position of one or both testicles can continue until irreversible disorders occur in them.

With cryptorchidism, there is a risk of developing a number of complications that require urgent surgical intervention: strangulation of the hernia accompanying cryptorchidism; torsion of the undescended testicle. Long-term dystopia of the testicle contributes not only to the disruption of its functions, but also to the occurrence of malignant degeneration. Cryptorchidism is often accompanied by underdevelopment of secondary sexual characteristics.

Symptoms of cryptorchidism are the absence of one or two testicles in the scrotum. Its hypoplasia (or half), absence of cremasteric reflex are revealed. In adolescents and men, symptoms of hypogonadism, spermatogenesis disorders and infertility may be observed.

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Forms

Depending on the degree of changes in the testicles, there are 4 types of undescended testicles in prepubertal boys:

• I - with minimal changes; the diameter of the tubules corresponds to age, contains a normal number of spermatogonia; the number of Sertoli cells, their morphology and ultrastructure are unchanged, mild hypoplasia of the tubules is rarely observed; after puberty, normal spermatogenesis and spermiogenesis occurs;
• Type II - characterized by a decrease in the number of spermatogonia, mild or moderate tubular hypoplasia with a normal Sertoli cell index (the number of Sertoli cells per tubular section); after puberty, a delay in spermatogenesis is observed at the stage of first- and second-order spermatocytes;
• Type III - pronounced hypoplasia of the tubules: a decrease in their diameter to 140-200 µm, a reduction in the number of spermatogonia and the Sertoli cell index; after puberty, only mature Sertoli cells are found in the tubules;
• Type IV - characterized by diffuse Sertoli cell hyperplasia, normal tubular diameter and few germ cells; after puberty, germ cells do not develop and Sertoli cells remain undifferentiated; the basement membrane and tunica propria thicken.

In unilateral cryptorchidism, the structure of the opposite testicle remains normal in 75% of patients. In other cases, the changes are the same as in the undescended testicle. Their nature depends on the location of the testicle: the lower and closer to the scrotum the testicle is located, the closer their structure is to normal, and vice versa. The most pronounced changes are found in testicles located in the usual location.

The number of Leydig cells is usually increased in individuals of pubertal and adolescent age. There are 4 types of cells:

• Type I - normal;
• Type II - with round nuclei, a large amount of cytoplasmic lipids and reduced GER; make up to 20-40% of the total number of Leydig cells in the testicle;
• Type III - pathologically differentiated cells with paracrystalline inclusions and
• Type IV - immature cells. Leydig cells of type I usually predominate.

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Treatment cryptorchidism

Treatment of cryptorchidism with gonadotropins, undertaken before puberty, is 50% effective. The prognosis of reproductive function depends on the age at which treatment is started.

At a conference on cryptorchidism convened by WHO in 1973, a recommendation was made for early treatment of dystopic testicles. It should be completed by the end of the child's 2nd year of life. The optimal treatment period is from the 6th to the 24th month.

During the first year of life, children receive 250 IU of hCG twice a week for 5 weeks. During the second year, 500 IU of the drug is administered twice a week for 5 weeks. If the time for early treatment is missed, the therapy is continued in the same doses until the age of 6. Starting from the age of 7, hCG is administered at 1000 IU twice a week for 5 weeks. Treatment with the drug is contraindicated if secondary sexual characteristics appear. A repeated course of hCG treatment is advisable only if obvious but insufficient success is noted after the first course. It is carried out 8 weeks after the end of the first course. Adult men are administered 1500 IU of hCG twice a week in monthly courses with monthly breaks.

If conservative treatment is ineffective, surgical treatment is indicated. The most favorable time for this is the 18th-24th month of the child's life.

The operation is necessary in cases where there is ectopia of the testicle, with concomitant hernia or cryptorchidism after herniotomy. It should be taken into account that the possibility of malignant degeneration of a dystopic testicle is 35 times higher than with its normal position.

In the last decade, it has become possible to treat cryptorchidism at an early age with cryptocur. The active principle of cryptocur is gonadorelin (gonadotropin-releasing hormone). This is a physiological releasing hormone (causing the secretion of both pituitary gonadotropins - LH and FSH). It stimulates not only the formation of LH and FSH in the pituitary gland, but also their secretion. Daily multiple intake of cryptocur imitates its physiological secretion by the hypothalamus, a regulated cycle occurs: hypothalamus - pituitary gland - gonads, specific in relation to age and gender, and the balance is regulated by the suprahypothalamic centers.

The concentration of T in the blood remains within the normal range typical for childhood. Treatment with cryptocur should be started as early as possible, preferably between the 12th and 24th month of life. The therapy can be carried out in older children. There are no contraindications for this. The drug is used intranasally: injected into each nostril 3 times a day for 4 weeks. After 3 months, the course of treatment can be repeated. A runny nose is not an obstacle to the use of cryptocur.

1 vial of Cryptocure contains 20 mg of synthetic gonadorelin as an active substance in 10 g of aqueous solution. The contents of the vial correspond to approximately 100 doses of aerosol (1 dose contains 0.2 mg of gonadorelin). Sometimes during treatment, excitability increases in children. Gonadorelin and gonadotropins or androgens should not be used simultaneously.