ADRENAL VIRILIZATION IS THE ACTUAL PROBLEM OF THE MODERN ENDOCRINOLOGY

ABSTRACT

The article presents a literary review of the pathology of the adrenal glands, called adrenal virilization. In 90% of cases, the development of the disease is associated with the absence of the hydroxylase enzyme. This leads to severe violations of hormone synthesis. Congenital adrenogenital syndrome occurs in 1 in 5,000 newborns. The disease is accompanied by an increase in the activity of the adrenal cortex and an increase in the concentration of male sex hormones, androgens, in the blood.

Keywords: virilization, androgen-secreting tumors, 21-hydroxylase, pregnantriol, cosyntropin, adrenocorticotropic hormone, glucocorticoids, adrenalectomy.

In adrenal virilization, the virilization syndrome is caused by excessive secretion of adrenal androgens. Diagnosis of the appearance and appearance of an increased level of androgens; identification of the cause may appear imaging of the adrenal glands. Treatment depends on the etiology of the disease.

The causes of adrenal virilism are as follows: Androgen-secreting adrenal tumors; Adrenal hyperplasia.

Adrenal cancers can secrete excess androgens, estrogens, cortisol, mineralocorticoids (or a combination of all four hormones). If there is excessive secretion of cortisol, this leads to the development of Cushing's syndrome with suppression of the secretion of adrenocorticotropic hormone (ACTH) and atrophy of the contralateral adrenal gland, as well as arterial hypertension. Tumors of the adrenal glands that secrete androgens cause virilization.

Hyperplasia of the adrenal glands is usually a congenital pathology; Postpubertal virilizing adrenal hyperplasia is a variant of congenital adrenal hyperplasia. Both diseases are caused by impaired hydroxylation of cortisol precursors, most commonly by a 21-hydroxylase deficiency or a much milder 11-beta-hydroxylase deficiency; cortisol precursors accumulate and are directed to the production of androgens. In postpubertal virilizing adrenal hyperplasia, this hydroxylation is only partially impaired, and clinical signs of the disease may appear only in adulthood.

In antenatal forms of the disease, the main clinical symptom is the visible virilization of the genitals. Newborn girls show signs of female pseudohermaphroditism. The clitoris is large in size or has a penis-like shape, the vestibule of the vagina is deepened, the urogenital sinus is formed, the large and small labia are enlarged, the perineum is high. The internal genital organs are developed normally.

In infant boys, the penis is enlarged and the scrotum is hyperpigmented. In addition, with salt-losing adrenogenital disorder, symptoms of adrenal insufficiency are expressed with severe, often incompatible with life, somatic disorders (diarrhea, vomiting, convulsions, dehydration, etc.), which manifest themselves from 2-3 weeks of age. In girls with simple viril adrenogenital syndrome, as they grow older, the signs of virilization intensify, a dysplastic physique is formed.

Due to the acceleration of ossification processes, the patients are characterized by short stature, broad shoulders, narrow pelvis, and short limbs. Tubular bones are massive. Puberty begins early (up to 7 years) and proceeds with the development of secondary male sexual characteristics. There is an increase in the clitoris, a decrease in the timbre of the voice, an increase in muscle strength, and the formation of the typical for men form of the cricoid cartilage of the thyroid gland. The breast does not grow, the menarche is absent.

Diagnosis of adrenal virilism: Determination of testosterone levels; Determination of levels of other adrenal androgens (dehydroepiandrosterone [DHEA] and its sulfate [DHEAS], androstenedione); 17-hydroxyprogesterone; Dexamethasone suppression test; Sometimes an adrenocorticotropic hormone (ACTH) stimulation test; Visualization of the adrenal glands.

Adrenal virilism may be suspected on the basis of clinical findings, although mild hirsutism and virilization with hypomenorrhea and elevated plasma testosterone levels also occur in polycystic ovary syndrome (Stein-Leventhal syndrome). The diagnosis is confirmed by an elevated level of adrenal androgens.

With adrenal hyperplasia, the content of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in the urine is increased; the excretion of pregnantriol (a metabolite of 17-hydroxyprogesterone) often also increases, while the level of free cortisol in the urine is normal or reduced. Plasma levels of DHEA, DHEAS, 17-hydroxyprogesterone, testosterone, and androstenedione are usually elevated. A 17-hydroxyprogesterone level > 30 nmol/L (1000 ng/dL) 30 minutes after IM administration of 0.25 mg cosyntropin (synthetic ACTH) is highly suggestive of the most common form of adrenal hyperplasia, 21-hydroxylase deficiency.

Suppression of excess androgen production with dexamethasone 0.5 mg orally every 6 hours for 48 hours eliminates a virilizing adrenal tumor. If excessive androgen excretion persists, then CT or MRI of the adrenal glands and ultrasound of the ovaries are performed in search of a tumor.

Treatment of adrenal virilization: The main way to correct virile dysfunction of the adrenal glands is hormone replacement therapy, which compensates for the deficiency of glucocorticoids. If a woman with latent AGS does not have reproductive plans, skin manifestations of hyperandrogenism are insignificant and menstruation is rhythmic, hormones are not used. In other cases, the choice of treatment regimen depends on the form of endocrine pathology, the leading symptoms and the degree of its severity. Often, the appointment of glucocorticoid drugs is supplemented with other medical and surgical methods, selected in accordance with a specific therapeutic goal: Infertility treatment. If there are plans for childbearing, a woman under the control of blood androgens takes glucocorticoids until the ovulatory monthly cycle is fully restored and pregnancy occurs. In resistant cases, ovulation stimulants are additionally prescribed. To avoid miscarriage, hormone therapy is continued until the 13th week of gestational age. Correction of irregular periods and virilization. If the patient is not planning a pregnancy, but complains of menstrual disorders, hirsutism, acne, drugs with estrogenic and antiandrogenic effects, oral contraceptives containing progestogens of the latest generation are preferred. Treatment of congenital forms of AGS. Girls with signs of false hermaphroditism undergo adequate hormone therapy and perform surgical correction of the shape of the genitals - cliterotomy, introitoplasty (opening of the urogenital sinus). In salt-losing adrenogenital disorders, in addition to glucocorticoids, mineralocorticoids are prescribed under the control of renin activity with an increase in therapeutic doses in the event of intercurrent diseases.

The prognosis for the timely detection of adrenogenital syndrome and adequately selected therapy is favorable. Even in patients with significant virilization of the genitals after plastic surgery, a normal sex life and natural childbirth are possible. Hormone replacement therapy for any form of AGS contributes to rapid feminization - the development of the mammary glands, the appearance of menstruation, the normalization of the ovarian cycle, and the restoration of generative function. Prevention of the disease is carried out at the planning stage of pregnancy.

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