Primary Congenital Hypogonadism (Anorchism)

What is Primary Congenital Hypogonadism (Anorchism)?

Congenital absence of testicles (born anorchism, anorchia, intrauterine anorchism) in pheno- and genotypic boys is a rare pathology: 1 in 20 thousand children. The etiology of anorchism syndrome is not clarified. Most often, the testicle dies at about the 20th week of intrauterine development, when the urethra is already formed in the male type, however, due to the absence of testicular androgens, cavernous bodies, the glans penis and scrotum remain completely absent (a “smooth crotch”). If the testicle dies after 20 weeks of fetal development, the external genitalia look like in bilateral abdominal cryptorchidism.

Causes of Primary Congenital Hypogonadism (Anorchism)

In the etiology of the syndrome, much attention is paid to diseases of a pregnant woman (toxicosis, injuries), possible testicular injury during childbirth in the buttock. In connection with the detection of antibodies to testicular tissue in such patients, a suggestion was made about the pathogenetic role of autoaggression.

Pathogenesis during Primary Congenital Hypogonadism (Anorchism)

In the pathogenesis of anarchism syndrome, the main role is played by the absence or a sharp decrease in testosterone secretion by the testes and a secondary increase in the secretion of gonadotropins. The level of testosterone in the blood both with congenital anorchism and with primary congenital bilateral testicular hypoplasia is markedly reduced (2–5 times) already in children from 8 to 10 years old.

Adolescents over 14 years of age with anorchism syndrome and primary hypoplasia of both testicles do not have a sharp increase in T in the blood, as is characteristic of healthy children. T remains at a low level, with age, this difference in indicators increases. Isolated cases of primary hypergonadotropic hypogonadism with normal or even elevated T levels in adolescents are described. This is explained by the possible low sensitivity of target organs to testosterone, and the absence of sexual differentiation disorders – by the heterogeneity of androgen receptors at different stages of ontogenesis. Thus, a high sensitivity of the tissues of the primary gonad to T in the embryonic and fetal periods is very likely, which leads to male differentiation of the genital tract, and a decrease in sensitivity in the postnatal period determines the clinic of hypogonadism in the subsequent development.

Violation of tissue sensitivity to T includes a violation of the sensitivity of the testicles, with gametogenesis to a greater extent, and steroidogenesis to a lesser extent. Violation of the sensitivity of target tissues to T leads to an increase in its circulation.

Anorchism syndrome is accompanied by an increase in FSH and LH levels without significant impairment of their dynamics up to 13 years. After 14 years, the FSH / LH ratio, in contrast to healthy ones, in which LH is 1.5 to 2 times higher than FSH, changes in favor of a significant prevalence of FSH. Remaining high, the level of pituitary hormones decreases with age.

In the pathogenesis of anorchism syndrome, a certain role is played by a violation of the hypothalamic-pituitary relations as a result of a possible loss of sensitivity of the hypothalamus to sex hormones. This explains the age-related decrease in the content of pituitary hormones with long-existing hypoandrogenism, the absence of a pituitary reaction (decreased gonadotropins) to exogenous testosterone, and the absence of an increase in the level of gonadotropins to the administration of clomiphencitrate.

The absence of testicles (anorchism) or pronounced bilateral hypoplasia of them causes the absence or a sharp decrease in the production of estradiol and an increase in the level of FSH in such patients. The content of testosterone-estradiol-binding protein is reduced. Hypoplasia extends to all structures of the testicles, spermatogenesis in such testicles is impossible. The adrenal androsteroids to some extent compensate for testicular hypoandrogenization, but they are not able to prevent the development of eunuchoidism by the pubertal period.

In the pathogenesis of metabolic disorders in anorchism syndrome, functional changes of other endocrine glands are included. The sensitivity of tissues to thyroidin is reduced. Paradoxical indicators of the level of somatotropic hormone are revealed: if in healthy adolescents the level of GH is slightly reduced compared to the pre-puberty period, then with anorchism, the level of GH is slightly reduced in pre-puberty, steadily increases in puberty and remains elevated in adults. Violation of lipid metabolism was established in such patients (increase in triglycerides, beta-lipoproteins, decrease in the ratio of beta-cholesterol to alpha-cholesterol). In connection with hypoandrogenia and a decrease in anabolic processes in the bone matrix, a number of patients have moderate osteoporosis, weakness of the ligamentous apparatus, and hypotension of the muscular system.

Symptoms of Primary Congenital Hypogonadism (Anorchism)

The clinical manifestations of congenital anorchism and congenital testicular hypoplasia are similar. They are characterized by an undeveloped (or absent) scrotum, the testicles are not palpable. A sharp underdevelopment of them with hypoplasia (less than 0.5 cm), an altered consistency often does not allow them to palpate. Palpation is often determined by vague formations or hypoplastic appendages.

Depending on when the testicle atrophied at utero (about 20 weeks or a little later), the appearance of the external genitalia at birth is different. In the first case, the penis is almost not developed, the scrotum is absent: the child is assigned a female passport gender, education is in the female direction. In the second case, the penis at birth is formed relatively normal, the scrotum is atrophied, empty. As a rule, a child is assigned a male gender, a male psychosexual orientation, eunuchoid features develop with age, in adolescents and adults, the prostate does not differentiate. A differential diagnosis with bilateral abdominal cryptorchidism is required. Revision of the inguinal canals or abdominal cavity, carried out with suspicion of bilateral abdominal cryptorchidism, allows almost always in case of anarchism to detect testicular elements, which brings together the pathogenesis and clinic of these conditions.

Up to 13-14 years old, a boy with anorchism and congenital testicular hypoplasia in his somatic development does not differ from healthy children, except for the presence of underdeveloped genitalia. And in those and others, the sizes of the penis at birth and before the age of ten do not differ significantly, and only after 10 – 11 years with anorchism the dynamics of penile growth is completely absent.

After 14 years, in boys with testicular hypoplasia, eunuchoid phenotype traits begin to form. The body continues to grow in length, mainly due to the lower extremities, the ratio of leg length to body length increases; in the future, gynoid traits are also acquired (the width of the pelvis prevails over the width of the shoulders), gradually, as a result of fat metabolism, female deposition of fat is enhanced.

The lack of testosterone inhibits the timely differentiation and ossification of the skeleton, prevents the development of secondary and tertiary sexual characteristics (the face is smooth, clean, without acne, there is no voice mutation, the thyroid cartilage does not increase). The skin is dry, pale, pasty. Patients are characterized by vegetovascular dystonia (fatigue, excessive sweating, drops in blood pressure, headaches, fainting), hypotension of the muscular system, and weakness of the ligamentous apparatus.

Patients have no or extremely rare erections, no pollutions, decreased interest in the opposite sex, adults are characterized by sexual weakness, infertility, the prostate is absent or sharply hypoplastic. Mental development without deviations from the norm, but due to fatigue, creative work causes certain difficulties. Often there is a high intelligence, there may be a “going to work” as a compensation for a physical handicap. Without psychotherapeutic training, it is not uncommon for a teenager, and even an adult, to have features of a depressed state, isolation, inner suffering, a sense of inferiority, and the impossibility of happiness. Deviations from the internal organs are absent.

Diagnosis of Primary Congenital Hypogonadism (Anorchism)

The absence or sharp hypoplasia of the testicles identified at birth is oriented towards determining the genetic gender. With anorchism syndrome, sex chromatin is negative, karyotype 46XY, there is no violation of sexual differentiation. In pre-puberty there is no typical picture of eunuchoidism, differential diagnosis is carried out with abdominal bilateral cryptorchidism according to the results of selective testicular venography, pelviography, a negative test for hCG, hormonal studies (high levels of gonadotropins).

At the final stage of diagnosis, revision of the inguinal canal and laparotomy are possible. At puberty and older, the main diagnostic criteria are the characteristic appearance of the eunuch, the absence of the prostate and testes with the normal karyotype 46XY, low T, high – LH, FSH, negative choriogonin test.

Primary Congenital Hypogonadism Treatment (Anorchism)

The tactics of treatment for anorchism syndrome depend on the severity of clinical manifestations, the sensitivity of target tissues to replacement androgen therapy, psychosexual orientation. A teenager should not be too ignorant of his defect. If it is detected early (up to 2 years), especially if there is a smooth crotch and unformed cavernous bodies of an undeveloped penis, it is advisable to educate the female in the direction with appropriate genital correction and estrogen replacement therapy.

In the presence of a sufficiently formed penis, the child is usually assigned a male gender, in which they are brought up, and therapeutic tactics with a timely diagnosis are aimed at correcting disorders of pubertal development. The doctor, together with parents and teachers, must timely conduct the psycho-prophylaxis of the depressive state, which may arise as a result of the sudden discovery of a physical disability, when he or his peers begin to pay attention to his unusual appearance.

The focus of treatment depends significantly on sensitivity to androgeps. With a male psychosexual orientation, a relatively developed penis and a positive reaction to androgens, it is advisable to preserve the male sex, and carry out replacement therapy with androgens.

Androgen therapy may not always be effective. In order to ensure sexual and social rehabilitation of patients with severe androgen deficiency in primary hypogonadism, autotopic testicular transplantation on the arteriovenous leg is successfully used. In case of insufficient sensitivity to androgens, small penis sizes corresponding to intrauterine ones, that is, in the absence of hope for the possibility of playing a male role during sex, with a pronounced eunuchoid structure of the skeleton with the addition of gynoid features in the distribution of subcutaneous fat, it is desirable to reorient the patient to change sex from surgical and hormonal correction in the female direction.