Adrenogenital syndrome - Causes, symptoms and treatment. MF.

Forms of adrenogenital syndrome:

In clinical practice, depending on the degree of C21-hydroxylase deficiency and, correspondingly, the degree of hyperandrogenism, the classical form of congenital adrenogenital syndrome and light forms, also called nonclassical( pubertal and post-puertata forms) are distinguished. Excessive secretion of androgens by the adrenal glands inhibits the release of gonadotropins, which results in a disruption in the growth and maturation of follicles in the ovaries.

Classical form of congenital adrenogenital syndrome

Hyperproduction of androgens begins in utero with the onset of hormonal adrenal function - the 9-10th week of intrauterine life. Under the influence of an excess of androgens, the sexual differentiation of the fetus of the female chromosomal sex is disrupted. During this period of pre-natal life, the gonads already have a distinct sexual identity, the internal sexual organs also have a structure inherent in the female sex, and the external genitalia are in the process of formation. From the so-called neutral type, a female phenotype is formed. Under the influence of excess testosterone, virilization of the external genital organs of the female fetus occurs: the sexual tubercle increases, becoming a penis-like clitoris, the labia-sacral folds merge into a scrotum, the urogenital sinus does not separate into the urethra and the vagina, but persists and opens under the penis-like clitoris. Such virilization leads to an incorrect definition of sex at the time of the birth of the child. Since gonads have a female structure( ovaries), this pathology has received yet another name - false female hermaphroditism. Hyperproduction of androgens in the intrauterine period causes hyperplasia of the adrenal glands;this form of adrenogenital syndrome is called the classical form of congenital adrenal hyperplasia.

Such children are patients of pediatric endocrinologists, tactics of their management and treatment is developed, which allows timely surgical correction of sex and direct further development of the female type.

The contingent of referring to gynecologists-endocrinologists are patients with late forms of adrenogenital syndrome.

Pubertal form of adrenogenital syndrome( congenital adrenal cortex dysfunction)

In this form of adrenogenital syndrome, the congenital deficiency of C21 hydroxylase is manifested in the pubertal period, during the period of physiological enhancement of the hormonal function of the adrenal cortex, in the so-called adrenarche period, 2-3 years ahead ofmenarche - the onset of menstruation. Physiological increase in the secretion of androgens at this age provides a puberty "growth spurt" and the appearance of sexual embryology.

The clinical picture is characterized by late menarche, the first menstruation comes in 15-16 years, whereas in the population it is 12-13 years. The menstrual cycle is unstable or irregular with a tendency to oligomenorrhea. The interval between monthly is 34-45 days.

Hirsutism has a pronounced character: the growth of the core hair is noted on the white line of the abdomen, on the upper lip, the sucking-in fields, and the inner thighs. There are multiple acne in the form of suppurated hair follicles and sebaceous glands, the facial skin is oily, porous.

Girls are characterized by high growth, the physique has a mildly expressed masculine or intersexual traits: broad shoulders, narrow pelvis.

Mammary glands are hypoplastic.

The main complaints leading the patients to the doctor are hirsutism, acne and unstable menstrual cycle.

Postpubertal form of adrenogenital syndrome

Clinical manifestations manifest at the end of the second decade of life, often after a spontaneous miscarriage at an early pregnancy, undeveloped pregnancy or medical abortion.

Women note a menstrual irregularity in the type of lengthening of the intermenstrual interval, a tendency to delays and a decrease in the monthly.

Since hyperandrogenism develops late and has a "mild" character, hirsutism is expressed only slightly: sparse hairiness of the white line of the abdomen, otolososovyh fields, above the upper lip, legs.

The mammary glands are developed according to age, the physique is of a purely feminine type.

It should be noted that patients with adrenogenital syndrome do not have metabolic abnormalities characteristic of polycystic ovary syndrome.

Causes of adrenogenital syndrome

The main cause of the onset is congenital deficiency of the enzyme C21-hydroxylase, which is involved in the synthesis of androgens in the adrenal cortex. The normal formation and content of this enzyme is provided by a gene localized in the short arm of one of the pair of the 6th chromosome( autosomes).The inheritance of this pathology is of an autosomal recessive nature. In the carrier of one pathological gene, this pathology can not be manifested, it manifests in the presence of defective genes in both autosomes of the 6th pair.

Diagnosis of adrenogenital syndrome

In addition to anamnestic and phenotypic data( physique, hair, skin condition, development of the mammary glands), hormonal studies are crucial in establishing the diagnosis.

With adrenogenital syndrome, the synthesis of steroids is disrupted in stage 17-ONP.Therefore, hormonal signs are an increase in blood levels of 17-ONP, as well as DEA and DEA-C - testosterone precursors. For diagnostic purposes, the determination of 17-CS in urine-androgen metabolites can be used.

The most informative is an increase in the level of 17-OHP and DEA-C in the blood, which is used for differential diagnosis with other endocrine disorders, manifested by symptoms of hyperandrogenism. The determination of 17-ONP, T, DEA, DEA-C in the blood, and 17-CS in the urine is performed before and after a sample with glucocorticoids, for example, dexamethasone. A decrease in the level of these steroids in blood and urine by 70-75% indicates an adrenal origin of androgens.

Diagnostic value has also an ultrasound of the ovaries. Since anovulation takes place in the adrenogenital syndrome, the presence of follicles of various degrees of maturity that do not reach preovulant sizes, the so-called multifollicular ovaries, echoscopically, the size of the ovaries may be somewhat higher than normal. However, unlike ovaries in the syndrome of polycystic ovaries, they do not increase the stromal volume and there is no typical arrangement of small follicles in the form of a "necklace" under the ovarian capsule.

The measurement of basal temperature, for which the stretched first phase of the cycle and the shortened second phase of the cycle( malnutrition of the yellow body) are characteristic, also have a diagnostic value.

Differential diagnosis of adrenogenital syndrome

Differential diagnostic signs of adrenogenital syndrome and polycystic ovary syndrome

Indicators

Treatment of adrenogenital syndrome

For the purpose of correcting the hormonal function of the adrenal glands, glucocorticoid drugs are used.

Currently, prescribe dexamethasone in a dose of 0.5-0.25 mg.per day under the control of blood androgens and their metabolites in the urine. The effectiveness of therapy is indicated by the normalization of the menstrual cycle, the appearance of ovulatory cycles, which is recorded by measuring basal temperature, data from the endometrial and ovarian echoscopy in the middle of the cycle, the onset of pregnancy. In the latter case, glucocorticoid therapy continues to avoid interruption of pregnancy until the 13th week - the time of formation of the placenta, providing the necessary level of hormones for normal fetal development.

During the first weeks of pregnancy careful monitoring is necessary: ​​up to 9 weeks - measuring the basal temperature, once every two weeks - ultrasound for detecting increased tone of the myometrium and echoscopic signs of detachment of the fetal egg. In case of spontaneous abortions, an estrogen-containing medication is prescribed to improve the blood supply of the developing embryo: microfoline( ethinyl estradiol) 0.25-0.5 mg per day or proginova 1-2 mg per day under the control of a woman's condition and her complaints of pain at the bottombelly, spotting from the genital tract.

Currently, in the treatment of miscarriage with adrenogenital syndrome in the I-II trimester of pregnancy, the use of the analog of natural progesterone - duftaston at 20-40-60 mg per day is effective. As a derivative of dydrogesterone, it does not possess an androgenic effect, unlike the progestogens of the norsteroid series, which is manifested by signs of virilization in the mother and masculinization in the fetus of the female. In addition, the use of dyufastone is effective in the treatment of functional ischemic-cervical insufficiency, often associated with adrenogenital syndrome.

In case of absence of pregnancy( ovulation or deficiency of the yellow body, recorded from basal temperature data) it is recommended against the background of glucocorticoid therapy to stimulate ovulation with clomiphene according to the generally accepted scheme: from the 5th to the 9th or from the 3rd to the 7th day of the cycleon 50-100 mg.

In cases where a woman is not interested in pregnancy, and the main complaint is excessive hair loss, pustular skin rashes or irregular menstruation, therapy with preparations containing estrogens and antiandrogens is recommended( see Treatment of hirsutism in PCOS).Most often prescribed drug Diane-35.It is more effective in the case of hirsutism against the background of diane in the first 10-12 days of its administration, administering cyproterone acetate in a dose of 25-50 mg( androkur preparation).The use of these drugs for 3-6 months gives a pronounced effect. Unfortunately, after the end of the medication the symptoms of hyperandrogenia appear again, because the reason for the pathology does not eliminate this therapy. It should also be noted that the use of glucocorticoids, normalizing the function of the ovaries, has little effect on reducing hirsutism. Anti-androgenic effect has oral contraceptives, which include progestins of the last generation( desogestrel, gestoden, norgestimate).Of non-hormonal drugs effective veroshpiron, which at a dose of 100 mg per day for 6 months or more reduces hirsutism.

With late post-pubertal form of adrenogenital syndrome, with mildly expressed cutaneous manifestations of hyperandrogenia and an unstable menstrual cycle without prolonged delays, the patients, if they are not interested in pregnancy, do not need hormone therapy.

When using hormonal contraceptives, preference is given to low-dose monophasic( mercilone) and three-phase with the gestagenic component of the last generation( desogestrel, gestodene, norgestimate), which do not have an androgenic effect. Long-term use of single-phase hormonal contraceptives containing 30 mcg of ethinylestradiol such as marvelon or femodena( more than a year without interruption) can cause hyper-inhibition of ovarian function and amenorrhea caused by hypogonadotropic disorders, rather than hyperandrogenism.