Hypogonadism Isolated (Idiopathic)

What is Isolated (Idiopathic) Hypogonadism?

Isolated (idiopathic) hypogonadism is the only form of hypogonadism in which only the reproductive system is affected. It occurs in the form of either a total deficit of gonadotropic hormones, or an isolated deficiency of LH or FSH. It occurs with the same frequency as anorchism.

Causes of Hypogonadism Isolated (Idiopathic)

The cause of this disease has not been fully elucidated. A hereditary predisposition is not peculiar to him or is observed extremely rarely.

More often, anamnestic data are revealed that indicate an unfavorable pregnancy in the mother (early, late toxicosis, professional contact with chemical harmful substances, mother taking medications, estrogen, high doses of progesterone during pregnancy). These drugs reduce the concentration of gonadotropins in the blood. The feminizing effect of reserpine was experimentally established and observed in the hypothalamic centers as a result of depletion of catecholamine (CA) reserves in the hypothalamus. A certain role is assigned to difficult births complicated by fetal asphyxiation. The role of fetal hypoxia in reducing the functional activity of the hypothalamus in nephropathies with impaired placental function producing chorionic gonadotropin has been established. Analysis of these data allows us to consider the most probable intrauterine origin of hypogonadism and to assume that its idiopathic form arises as a result of harmful effects on the hypothalamic-pituitary system before birth, that after birth it is more resistant to damaging factors, and if this happens, then the pathological process captures other functions of the pituitary gland.

Pathogenesis during Hypogonadism Isolated (Idiopathic)

Most often, patients are found with a simultaneous decrease in gonadotropic hormones (LH and FSH), somewhat less often with an isolated decrease in LH (Pasqualini syndrome, fertile eunuch syndrome), and even less often with isolated FSH deficiency. It is assumed that the total deficit of LH and FSH is associated with damage to the hypothalamus, since the test with the antiestrogen clomiphencitrate turned out to be negative, i.e. the pituitary gland continued to produce LH and FSH in the same small amounts as before the test. It is also assumed that the hypothalamus-pituitary gland relationship persists in such patients, estrogens simply metabolized in the hypothalamus did not respond to the inhibitory effect of clomiphencitrate, and its stimulating effect on the secretion of gonadoliberin mediated through testosterone did not “work”.

In isolated LH or FSH deficiency, the pituitary gland is primarily damaged. In adolescents with isolated LH deficiency, a test with clomiphencitrate leads to a significant increase in FSH, and with isolated FSH deficiency, an increase in LH. The reason for this partial hypogonadotropic hypogonadism is the inferiority of the pituitary gonadotrocytes producing one or another hormone. A test with gonadoliberin also allows to differentiate the cause of the disease – with a combination of LH and FSH deficiency it is positive (pathology in the hypothalamus), with isolated LH and FSH deficiency – it is selectively negative and confirms the inability of damaged gonadotropocytes to respond to hypothalamic stimulation.

The chronic state of gonadotropin deficiency causes a decrease in the production of T by the testes, which is especially noticeable with age, but does not violate the metabolism of T in them (the ratio of T to EP remains normal). This metabolism of T with gonadotropic hypogoyadism differs from the metabolism of T with anorchism.

To some extent, androgenic reserves are preserved in the testes, they are able to respond by increasing T to prolonged administration of hCG (a three to five-day test is positive), but they do not respond to short-term exposure (a single dose of 2000 IU / m of body surface) due to a decrease in them are the concentrations of LH receptors.

With isolated or predominant FSH deficiency, even a three-day hCG stimulation does not increase the normal level of LH, which may indicate its latent deficiency, Menopausal gonadotropin (PGH), which has FSH activity, and its combined use with hCG gives an increase in LH, FSH and T in circulation .

With this form of the disease, there were no significant morphological changes in the hypothalamic-pituitary region, nor are there clinical signs of a central nervous system disorder – unlike other forms of hypogonadotropic hypogonadism that occur against the background of gross changes in the hypothalamus, pituitary, and diencephalon.

With hypogonadotropic hypogonadism in testicular biopsies, a large number of seminiferous tubules are revealed, lined with immature Sertoli cells and spermatogonia, mainly of the infantile type E. Primary spermatocytes are rarely found.

Symptoms of Isolated (Idiopathic) Hypogonadism

Total hypogonadotropic (idiopathic) hypogonadism with hypoplasia of the interstitial apparatus, tubules, Sertoli cells up to puberty manifests itself as pronounced hypogenitalism (micropenis), often with pseudocryptorchidism, small, soft (rarely dense), weakly sensitive to palpation testes. Children are characterized by early (up to 14-16 years old) formation of a eunuchoid appearance (earlier than under anorchism), increased growth due to lower extremities, complete absence of secondary sexual characteristics even at 16, female fat deposition with signs of false gynecomastia, feminizing teenage figure, delayed development of sexuality. In adults with secondary hypogonadism, there are practically no erections, there are never any emissions, aspermia, infertility, extragenital signs of hypoandrogenism are observed: vegetovascular dystonia, headaches, fatigue, decreased performance, varicose veins of the lower extremities.

Classical total hypogonadotropic hypogonadism has common features with anorchism syndrome: eunuchoidism traits, extragenital signs of hypoandrogenization, the absence of clinically pronounced signs of central nervous system disorders, asthenia, vegetovascular dystonia without somatic disorders, similar psycho-behavioral features.

Partial deficiency of gonadotropins, respectively, affects the characteristics of clinical manifestations.

A clinic for isolated LH deficiency is described as Pasqualini syndrome or fertile eunuch syndrome. In childhood and adolescence, clinical signs are similar to the picture of hypogonadotropic eunuchoidism, the symptomatology depends on the degree of decrease in LH and the severity of hypoandrogenin and is manifested by micropenis, eunuchoid body proportions, poor sexual hair growth, impaired potency, decreased fertility. The level of LH is low, FSH is within normal limits. According to the spermogram, oligozoospermia, impaired sperm motility, reduced fructose are detected. Karyotype 46XY. Patients are able to have children, although they sometimes go to the doctor due to infertility, which depends on the deficiency of androgens that provoke hypospermia.

With isolated FSH deficiency in adults, a normally developed penis, well-defined secondary sexual characteristics, normal potency, slightly hypoplastic testicles, oligo- and azoospermia are noted. In connection with the preserved sexual function and normal appearance, patients rarely go to the doctor, not considering themselves guilty of a fruitless marriage. The level of FSH is reduced, LH is normal.

In children and adolescents with an isolated FSH deficiency, eunuchoid proportions of the body are less pronounced, the penis is better developed than with the above two forms, the testicles are dense, slightly sensitive to palpation, and late appearance of scanty hair growth.

There is some similarity with anorchism syndrome, which is exacerbated by negative choriogonin breakdown. In differential diagnosis, a test with PGM helps. FSH deficiency adversely affects the state of interstitial endocrinocytes, causing, although late, a clinic of hypoandrogenia and once again testifying to the synergistic effect of both gonadotropic hormones.

Hypogonadism Treatment of Isolated (Idiopathic)

Treatment with total hypogonadotropic hypogonadism is carried out with chorionic gonadotropin at a dose of 1500-2000 units intramuscularly 2 times a week for a month, with monthly breaks throughout the reproductive period. In this case, the use of androgens is useful, namely, the treatment of hCG (1500 IU intramuscularly every other day), as a pathogenetic method, after 12-24 months of treatment gave a positive effect on the formation of sperm cells in patients with azoospermia, while the use of testosterone propionate and separately, and in combination with PGM did not give a therapeutic effect. For the treatment of coded LH or FSH, a combination of hCG and PGM is useful.