Secondary hypogonadism

Secondary hypogonadism, or hypogonadotropic hypogonadism, most often occurs as a result of primary gonadotropic deficiency, which may be combined with deficiency of other pituitary tropic hormones. In isolated gonadotropic deficiency, the leading clinical symptoms are caused by low androgen levels, as in the case of primary hypogonadism.

[ 1 ], [ 2 ], [ 3 ], [ 4 ]

Causes secondary hypogonadism

The most common causes of hypopituitarism are tumors, vascular disorders, inflammatory processes in the pituitary gland and hypothalamus, as well as operations on the former. There are also congenital forms of secondary hypogonadism with disorders of the embryonic development of the pituitary gland. In the plasma of these patients, low levels of gonadotropins (LH and FSH) and testosterone are noted.

[ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ]

Symptoms secondary hypogonadism

Hypogonadotropic hypogonadism is characterized by a decrease in the size of the testicles due to hypoplastic and atrophic changes in the organ parenchyma. The seminiferous tubules are reduced in size, lack a lumen, and are lined with Sertoli cells. Spermatogonia are rare. Spermatogenesis, if observed, is only up to the stage of first-order spermatocytes. Only precursors of Leydig cells are found in the interstitium.

The severity of symptoms of hypogonadism depends on the degree of pituitary insufficiency and the age at which the disease occurs.

Forms

[ 10 ], [ 11 ], [ 12 ], [ 13 ], [ 14 ]

Congenital secondary hypogonadism

Kallman syndrome is characterized by gonadotropin (luteinizing hormone and FSH) deficiency, hyposmia, or anosmia (decreased or absent sense of smell). These patients have a congenital defect in the development of the hypothalamus, manifested by a deficiency of gonadotropin-releasing hormone, which leads to decreased production of gonadotropins by the pituitary gland and the development of secondary hypogonadotropic hypogonadism. An accompanying defect in the formation of the olfactory nerves causes anosmia or hyposmia.

Clinically, these patients have eunuchoidism, which is sometimes accompanied by cryptorchidism. In addition, they have such defects as cleft lip ("harelip") and palate ("cleft palate"), deafness, syndactyly (six-fingeredness), etc. The disease is familial, so from the anamnesis it can be found out that some family members have or had the described developmental defects. The karyotype of patients is 46.XY. The plasma has a low content of luteinizing hormone, FSH and testosterone.

Treatment of Kallman syndrome consists of long-term administration of chorionic gonadotropin or its analogues (profasi, pregnyl, choriogonin, etc.) at 1500-2000 U 2-3 times a week intramuscularly - monthly courses with monthly breaks. In case of severe testicular hypoplasia, along with chorionic gonadotropin, androgens are also administered: injections of sustanon-250 (or omnadren-250) at 1 ml once a month or testenate 10% at 1 ml every 10 days for a year. If the patient's blood testosterone level is sufficient as a result of treatment with gonadotropin alone, treatment with chorionic gonadotropin alone (or its analogues) is possible.

It leads to the development of secondary sexual characteristics, penis enlargement, and normalization of the copulative function. To restore reproductive function, it is possible to use gonadotropins with greater follicle-stimulating activity: humegon, pergonal, neopergonal intramuscularly at 75 IU (in combination with pregnyl or another analogue at 1500 IU) 2-3 times a week for 3 months. Further use of these drugs depends on the effectiveness of the treatment. Fertility is sometimes restored.

Isolated deficiency of luteinizing hormone manifests itself with symptoms characteristic of androgen deficiency. The leading role in the development of this pathology is given to congenital deficiency of luteinizing hormone production and decreased secretion of testosterone. The decrease in the concentration of fructose in the ejaculate observed in these patients, as well as the decrease in sperm motility, are manifestations of androgen deficiency.

The plasma FSH level in most cases remains within the normal range, which explains the preservation of all stages of spermatogenesis. Oligospermia observed in this condition is apparently associated with androgen deficiency. Pasqualini was the first to report such patients in 1950. They had a clearly expressed clinical picture of eunuchoidism and, at the same time, satisfactory spermatogenesis. Such cases of "fertility" in patients with hypogonadism were called "Pasqualini syndrome" or "fertile eunuch syndrome". The latter is unfortunate, since fertility is impaired in most cases.

Symptoms depend on the severity of the luteinizing hormone deficiency. This syndrome is characterized by underdevelopment of the penis, sparse pubic, armpit and facial hair, eunuchoid body proportions, and impaired sexual function. Patients rarely have gynecomastia and do not have cryptorchidism. Sometimes they consult a doctor about infertility. The results of ejaculate examination are usually uniform: small volume, oligospermia, low sperm motility, and a sharp decrease in fructose content in seminal fluid. Karyotype 46.XY.

Treatment of isolated luteinizing hormone deficiency is advisable to treat with chorionic gonadotropin or its analogues (pregnyl, profazi, etc.) at 1500-2000 IU intramuscularly 2 times a week - monthly courses with monthly breaks throughout the reproductive period of life. As a result of the treatment, both copulative and reproductive functions are restored.

Maddock syndrome is a rare disorder resulting from simultaneous deficiency of the gonadotropic and adrenocorticotropic functions of the pituitary gland. It manifests itself after puberty. Low levels of luteinizing hormone, FSH, ACTH and cortisol in the blood. Low levels of 17-OCS in the urine. When human chorionic gonadotropin is administered, the level of testosterone in plasma increases. Thyrotropic function is preserved. The etiology of this disorder is unknown.

Symptoms. Patients develop a clinical picture of eunuchoidism in combination with signs of chronic adrenal insufficiency of central genesis, therefore there is no hyperpigmentation of the skin and mucous membranes, which is typical for secondary hypocorticism. The literature contains descriptions of isolated cases of this pathology.

Treatment of such patients is carried out along with gonadotropins according to the usual scheme: with drugs that stimulate the function of the adrenal cortex (corticotropins), or with the help of glucocorticoid replacement therapy.

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

Acquired secondary hypogonadism

These forms of the disease can develop after infectious and inflammatory processes in the hypothalamic-pituitary region. Thus, in patients who have had tuberculous meningitis, in some cases, signs of hypogonadism develop, accompanied by the loss of other pituitary functions (thyrotropic, somatotropic), sometimes - polydipsia. During an X-ray examination of the skull, in some patients, inclusions of petrifications can be detected above the sella turcica - an indirect sign of a tuberculous process in the hypothalamic region. Forms of secondary hypogonadism are subject to replacement therapy according to the scheme described above. In addition, such patients are shown replacement therapy with those hormones, the deficiency of which is present in the body.

Adiposogenital dystrophy

It can be considered an independent disease only if its symptoms appeared in childhood and the cause of the disease could not be determined. Symptoms of this pathology can develop with organic lesions of the hypothalamus or pituitary gland (tumor, neuroinfection). When establishing the nature of the process damaging the hypothalamus (inflammation, tumor, injury), obesity and hypogonadism should be considered as symptoms of the underlying disease.

Dysfunction of the hypothalamus leads to a decrease in the gonadotropic function of the pituitary gland, which in turn leads to the development of secondary hypogonadism. Adiposogenital dystrophy is most often detected in prepubertal age (at 10-12 years). The syndrome is characterized by general obesity with the deposition of subcutaneous fat according to the "female type": in the abdomen, pelvis, trunk, face. Some patients have false gynecomastia. The body proportions are eunuchoid (wide pelvis, relatively long limbs), the skin is pale, hair on the face, in the armpits and on the pubis is absent (or very scanty). The penis and testicles are reduced in size, some patients have cryptorchidism. Diabetes insipidus is sometimes detected.

[ 20 ], [ 21 ], [ 22 ], [ 23 ], [ 24 ]

Treatment secondary hypogonadism

Treatment of hypogonadism in adiposogenital dystrophy: injections of human chorionic gonadotropin or its analogues (pregnyl, profasi, etc.) from 1500 to 3000 IU (depending on the severity of obesity) are used 2 times a week in monthly courses with monthly breaks. If the effect of gonadotropin therapy is insufficient, androgen injections can be prescribed simultaneously: sustanon-250 (or omnadren-250) 1 ml once a month or injections of 10% testenate 1 ml every 10 days. If the patient has impaired liver function, it is advisable to use oral medications: andriol 1 capsule 2-4 times a day. Weight loss measures must be taken: subcaloric diet, appetite suppressants, exercise therapy.