Cryptorchidism

Cryptorchidism is a condition where one or both testicles are not lowered into the scrotum. Cryptorchidism is often the cause of the disruption of the hormonal and reproductive function of testicles. With normal physiological development, they are already in the scrotum when the child is born or by the end of the first year of life. This is a prerequisite for their normal functioning.

[1]

Epidemiology

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

[2], [3], [4], [5], [6], [7], [8]

Causes of the cryptorchidism

Factors that cause 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, lack of a directing ligament and its intra-abdominal fusion, hypoplasia of the spermatic artery, insufficient blood supply of testicles, hernia.
2. Hormonal insufficiency, depending on many reasons. The violation of the process of lowering testicles depends on the insufficient stimulation of Leydig cells by the maternal chorionic gonadotropin. The change in the gonadotropic function of the hypothalamic-pituitary system leads to deficiency of differentiating hormones and to gonadal dysgenesis. Later, during the postnatal development, the dysplastic-dystrophic phenomena in the undescended testicle progress. Additional factors are the violation of the temperature regime and the distortion of enzymatic processes in the testicle tissue. The constant traumatization of these leads to the accumulation of antibodies in the blood and the development of autoaggression. Autoimmune conflict aggravates the defeat of the testicle parenchyma.
3. Endogenous developmental disorders of testicles, a decrease in their sensitivity to hormones. The process of lowering testicles depends not only on stimulation, but also on the sensitivity of Leydig's embryonic cells to the maternal gonadotropin, such as in case of incomplete masculinization syndrome, or the lack of sensitivity of target organs to androgens (in testicular feminization syndrome), and also from the state of other sensory organs (directing ligament, vas deferens, etc.).

[9], [10], [11], [12]

Pathogenesis

It has been experimentally proved that the lowering of the testicles in the scrotum is regulated by hormones: the maternal chorionic gonadotropin stimulates the secretion of androgens in the embryonic testicles, and the androgens secreted by the Leydig embryonic cells cause the growth of the vas deferens and the seminiferous tubules of the epididymis, testis and ligament. Thus, the entire normal process of forming and lowering the testicles into the scrotum, starting from the correct placement of the sex, is determined by the set of chromosomes, fetal hormones of the fetus, the chorionic gonadotropin of the mother, and the luteinizing hormone of the fetus. The whole process ends in the period from 6 months of intrauterine life to the 6th week of postnatal life.

As the accumulation of clinical experience, more and more data appear, indicating the possibility of combining various diseases with cryptorchidism. Currently, there are more than 36 syndromes (like, for example, Callman's syndrome) and diseases accompanied by cryptorchidism. Only in cases when he (or ectopia of testicles) is the only developmental anomaly, the diagnosis of cryptorchism as an independent disease is authorized.

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

[13], [14], [15], [16], [17], [18], [19]

Symptoms of the cryptorchidism

Cryptorchidism is divided into congenital and acquired, one- and two-sided; at the location of testicles - on the abdominal and inguinal forms. True cryptorchidism is always accompanied by underdevelopment of one half or all of the scrotum. This symptom was described in 1937 by Hamilton. The testicle sticks in the way of lowering and can be located in the abdominal cavity (abdominal cryptorchism) or, which is more common, in the inguinal canal (inguinal cryptorchidism). At 1-3% of all suffering cryptorchidism there is monarchism and anarchism.

With unilateral cryptorchidism, the reproductive and hormonal function is performed by a single testicle, which is pubescent in the scrotum.

The inguinal form of true cryptorchidism should be distinguished from pseudochriptorchism (a migrating testicle), in which a normally lowered testicle can periodically be outside the scrotum under the influence of a strong contraction of the muscle lifting it (a strong cremaster reflex). When palpation, this testicle is easily reduced to the scrotum. Close to cryptorchidism is the ectopia of the testicle. If its incomplete migration leads to cryptorchidism, then deviation from the path of descent leads to an ectopia, that is, to its unusual location. Passing the inguinal canal, the testicle does not fall into the scrotum, but is located under the skin in any of the adjacent areas.

This pathology is promoted by birth defects of the directing ligament. Distinguish between prefascial (testis refluxus) and superficial inguinal ectopia. The canopy in this case has a normal length, but the testicle is displaced into the area in front of the inguinal canal. Differential diagnosis of cryptorchidism from ectopy is important in the choice of treatment tactics. If the first resort to hormonal treatment, then the second treatment is only surgical. Often without an operative release of the testicle, it is impossible to diagnose and distinguish the ectopic from true cryptorchidism. Intermediate, femoral and crossed ectopy are rare. Also, infrequently, both testicles can be in one half of the scrotum.

Both in congenital cryptorchidism and in experimental, the results were obtained, indicating that in degenerated testicles the degeneration of the spermatogenic epithelium occurs with a decrease in the diameter of the tubules, the number of spermatogonia, and the weight of the testicle. Changes were observed in all cells of the spermatogenetic series. The greatest defects were germ cells at higher levels of differentiation. With the help of histomorphometric analysis it was possible to prove that with cryptorchidism before the end of the second year of the child's life no developmental disorders in testicles occur. However, from this moment it can be noted an obvious change in the number of spermatogonia, as well as the narrowing of the seminiferous tubules in comparison with normal dimensions. Thus, with cryptorchidism and ectopia, testicular damage occurs after 2 years of life.

Normal  spermatogenesis is  carried out only at a certain temperature, which in men in the scrotum is 1.5-2 ° C below body temperature. The embryonic epithelium is very sensitive to it. Increased temperature of the testicles can lead to the cessation of spermatogenesis and infertility. Their displacement into the abdomen or inguinal canal, hot tubs, feverish diseases or a very high ambient temperature can cause degenerative changes in the germinal epithelium in men. Maintaining the optimal temperature of testicles is guaranteed only by placing them in the scrotum, which performs the thermoregulatory function. The degree of degenerative changes in the embryonic epithelium increases with the duration of overheating.

In accordance with the foregoing, it was proposed to begin treatment of cryptorchidism before the end of the second year of life. A good prognosis was noted even in those cases when cryptorchidism exists before the 7th year of life. Mechanisms that lead to a reduction or disappearance of the ability of the embryonic epithelium to reproduce are not yet clear to this day. There is an assumption that, along with the harmful effect of overheating on the mitotic ability of spermatogonia to fission in testicles with cryptorchidism, autoimmunological processes lead to degenerative epithelial damage.

Research A. Attanasio et al. Were devoted to the study of violations of hormonal regulation of spermatogenesis. The hormonal function of the testicles during the prebiergate period was studied under the influence of hCG (human chorionic gonadotropin). The secretion of T normal testicles was also compared with cryptorchidism. The possibility of stimulation of T secretion by testicles with cryptorchidism under the influence of hCG was revealed. Normal endocrine function of testicles is a condition for their normal lowering. With the elimination of pathology by treatment of hCG, testicles had a better fertilizing ability than testicles, whose cryptorchidism was eliminated operatively. Until now, it has not been fully determined how long the abnormal position of one or both testicles can last until the moment of irreversible disturbances in them.

With cryptorchidism there is a danger of developing a number of complications that require urgent surgical intervention: infringement of the hernia accompanying cryptorchidism; the inversion of an undescended testicle. Long-existing dystopia of the testicle contributes not only to the violation of its functions, but also to the onset of malignant degeneration. Often cryptorchidism is 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) is revealed, the absence of a cremaster reflex. Young men and men may have symptoms of hypogonadism, impaired spermatogenesis and infertility.

[20], [21]

Forms

Depending on the degree of manifestation of changes in the testicles, four types of unresponsive testes are distinguished in boys of pre-adherent age:

• 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 not changed, there is rarely a slight hypoplasia of the tubules; after puberty, normal spermato- and spermiogenesis occurs;
• II type - characterized by a decrease in the number of spermatogonia, mild or moderate hypoplasia of the tubules with a normal Sertoli-cell index (the number of Sertoli cells per shear of the tubule); after puberty there is a delay in spermatogenesis in the stage of spermatocytes of the first and second order; 
• III type - pronounced hypoplasia of tubules: a decrease in their diameter to 140-200 μm, a reduction in the number of spermatogonia and Sertoli-cell index; After puberty, only mature Sertoli cells are found in the tubules; 
• IV type - characterized by diffuse Sertoli-cell hyperplasia, normal tubule diameter and a few sex cells; After pubertal, the sex cells do not develop, and Sertoli cells remain undifferentiated; Basal membrane and tunica propria thicken.

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

The number of Leydig cells is usually increased in puberty and adolescence. There are 4 types of cells:

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

[22], [23], [24], [25]

Treatment of the cryptorchidism

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

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

At the 1st year of life, children receive HC 250 units twice a week for 5 weeks. In the second year, 500 units of the drug are administered 2 times a week for 5 weeks. If the time of early treatment is missed, then therapy continues in the same doses up to 6 years of age. Beginning from the age of 7 years, HC is injected at 1000 units twice a week for 5 weeks. Treatment with the drug is contraindicated with the appearance of secondary sexual characteristics. Repeated treatment of HC is advisable only if, after the first course, there is obvious but insufficient success. It is conducted 8 weeks after the end of the first course. Adult male HG is injected 1500 UU twice a week with monthly courses with monthly interruptions.

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

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

In the last decade, the possibility of treating cryptorchidism at an early age with cryptocurcs has emerged. The active principle of cryptocur is gonadorelin (gonadotropin-releasing hormone). It is a physiological releasing hormone (causing the secretion of both gonadotropins of the pituitary gland - LH and FSH). It stimulates not only the formation of LH and FSH in the pituitary gland, but also their secretion. Daily multiple reception of a cryptocurian imitates its physiological secretion by the hypothalamus, there is an adjustable cycle: the hypothalamus-pituitary-gonads, specific to age and sex, with equilibrium being regulated by the sub-hypothalamic centers.

The concentration of T in the blood remains within the normal range characteristic for childhood. Treatment with cryptocurium should be started as early as possible, best between the 12th and 24th month of the child's life. It is possible to carry out therapy in older children. There are no contraindications for this. The drug is applied intranasally: it is injected into each nostril 3 times a day for 4 weeks. After 3 months, the course of treatment can be repeated. Runny nose is not an obstacle to the use of cryptocure.

1 vial of cryptocure contains 20 mg of synthetic gonadorelin as active ingredient in 10 g of an aqueous solution. The contents of the vial correspond to approximately 100 doses of aerosol (1 dose of it contains 0.2 mg gonadorelin). Sometimes during treatment in children, the excitability increases. Do not use gonadorrelin and gonadotropins or androgens at the same time.