Adrenogenital syndrome in children

Congenital dysfunction of the adrenal cortex (synonym: adrenogenital syndrome in children) includes a group of hereditary enzymopathies. At the heart of each fermentopathy is a genetically determined defect of the enzyme involved in steroidogenesis.

Defects of five enzymes involved in the synthesis of gluco- and mineralocorticoids are described, and this or that variant of adrenogenital syndrome in children is formed. All forms of congenital dysfunction of the adrenal cortex are inherited in an autosomal recessive manner.

ICD-10 code

• E25 Adrenogenital disorders.
• E25.0 Congenital adrenogenital disorders associated with enzyme deficiency.
• Е25.8 Other adrenogenital disorders.
• E25.9 Adrenergic disorder, unspecified.

What causes adrenogenital syndrome in children?

A defect of 21-hydroxylase is observed in 90% of cases, which can be caused by different mutations of the CYP21 gene encoding this enzyme. Dozens of mutations of CYP21, leading to a P450c21 defect, are described. There is also a point mutation with a partial activity of 21-hydroxylase. With partial deficiency of this enzyme, a simple (virile) form of the disease develops. 21-hydroxylase is involved in the synthesis of cortisol and aldosterone and does not participate in the synthesis of sex steroids. Violation of the synthesis of cortisol stimulates the production of ACTH, which leads to hyperplasia of the adrenal cortex. In this case, 17-OH-progesterone, a precursor of cortisol, accumulates. The excess of 17-OH-progesterone is converted into androgens. Adrenal androgens lead to virilization of the external genitalia in a female fetus - a girl with a false female hermaphroditism is born. In boys, hyperandrogenemia determines the premature appearance of secondary sexual characteristics (a syndrome of premature sexual development).

With a significant deficit of 21-hydroxylase, the hyperplastic adrenal cortex does not synthesize cortisol and aldosterone in the required quantities. While against the background of hyperandrogenemia, a syndrome of salt loss or adrenal insufficiency develops, a salt-losing form of the disease.

The nonclassical form of 21-hydroxylase deficiency manifests itself in pre- and pubertal age in the form of adrenarche, mild hirsutism and menstrual irregularity in girls. Moderate or easy virilization is the result of a point mutation between V281L and P30L.

Symptoms of adrenogenital syndrome in children

With the classical viril form of adrenogenital syndrome in children, the external genital organs of the girl are formed by a heterosexual type - the clitoris is hypertrophied, the large labia resemble the scrotum, the vagina and urethra are represented by the urogenital sinus. In newborn boys, obvious violations can not be identified. From 2-4 years, children of both sexes have other symptoms of adrenogenital syndrome in children, i.e., androgenization: axillary and pubic hairiness develops, skeletal muscle develops, the voice becomes gross, the figure is masculinized, and youthful acne on the face and trunk appear. Girls do not grow mammary glands, menstruation does not appear. At the same time, the differentiation of the skeleton is accelerated, and the growth zones are closed prematurely, this causes a short stature.

With salt-losing form of 21-hydroxylase deficiency, in addition to the above-described symptoms, in children from the first days of life, signs of adrenal insufficiency are noted. Appear at the beginning of regurgitation, then vomiting, a loose stool is possible. The child quickly loses body weight, develops symptoms of dehydration, microcirculation disorders, lowers blood pressure, begins tachycardia, cardiac arrest due to hyperkalemia is possible.

The nonclassical form of adrenogenital syndrome in children is characterized by the early appearance of secondary hair, the acceleration of growth and differentiation of the skeleton. In girls of puberty, moderate signs of hirsutism, menstrual irregularities, and the formation of secondary polycystic ovaries are possible.

Insufficiency of 11-hydroxylase in contrast to 21-hydroxylase deficiency, in addition to the symptoms of virilization and androgenization, is accompanied by an early and persistent increase in blood pressure. It is caused by the accumulation in the blood of the aldosterone precursor, deoxycorticosterone.

Diagnosis of adrenogenital syndrome in children

[1], [2], [3], [4], [5], [6], [7], [8]

Laboratory diagnosis of adrenogenital syndrome in children

• All children with an irregular structure of the external genital organs, including boys with bilateral abdominal cryptorchidism, are shown to have a definition of sex chromatin and a karyotype study.
• From the first days of life in the blood serum of the patient, an increased content of 17-OH-progesterone is detected. It is possible to carry out a screening test for newborns on the 2nd-5th day of life - 17-OH-progesterone is increased several times.
• In the syndrome of salt loss, hyperkalemia, hyponatremia, hypochloraemia are characteristic.
• Urinary excretion of 17-ketosteroids (metabolites of androgens) increases.

Instrumental diagnosis of adrenogenital syndrome in children

• Bone age according to the radiograph of wrist joints outstrips the passport one.
• With ultrasound, girls have a uterus and ovaries.

Differential diagnosis of adrenogenital syndrome in children

In children of the first year of life, differential diagnosis of adrenogenital syndrome in children is carried out with various forms of false male hermaphroditism and true hermaphroditism. The reference point in diagnosis is karyotyping (karyotype 46XX with bisexual structure of external genital organs) and determination of 17-OH-progesterone in serum. The salt-losing form of congenital dysfunction of the adrenal cortex should be differentiated from pyloric stenosis, difficulties arise in the differential diagnosis of adrenogenital syndrome in children and pyloric stenosis in boys-in this case, the importance of hyperkalemia and the high level of 17-OH-progesterone in congenital dysfunction of the adrenal cortex.

In older children with symptoms of hyperandrogenemia, one should remember about androgen-producing adrenal or gonadal tumors.

[9], [10]

Treatment of adrenogenital syndrome in children

Medication for adrenogenital syndrome in children

The viral form of adrenogenital syndrome in children requires constant replacement therapy with prednisolone. The dose of the drug is selected individually depending on the age and degree of virilization and divided into 2-3 receptions. The doses are distributed evenly throughout the day. On average, the daily dose of prednisolone is 4-10 mg. This amount of the drug suppresses excessive production of androgens, without any side effects.

Treatment of the salt-losing form of adrenogenital syndrome in children with adrenal insufficiency failure is carried out in the same way as treatment of acute adrenal insufficiency by dropping the isotonic solution of sodium chloride and glucose, as well as parenteral administration of hydrocortisone preparations (10-15 mg / kg per day). The daily amount of hydrocortisone is distributed evenly. The drug of choice - water-soluble hydrocortisone (solukottef). When the condition is stabilized, hydrocortisone injections are replaced with hydrocortisone tablets, if necessary, mineralocorticoid-fludrocortisone (2.5-10.0 μg per day) is added.

Surgical treatment of adrenogenital syndrome in children

Girls at 4-6 years of age undergo a surgical correction of the external genitalia.

Criteria for the effectiveness of treatment of adrenogenital syndrome in children: normalization of child's growth rates, normal indices of blood pressure, electrolytes in blood serum. The optimal dose of glucocorticosteroids is determined by the level of 17-OH-progesterone in the serum, mineralocorticoids - by the content of renin in the blood plasma.

Prognosis of adrenogenital syndrome in children

The prognosis for life with timely diagnosis and proper treatment of adrenogenital syndrome in children is favorable. It should be remembered about the risk of developing acute adrenal insufficiency in injuries, intercurrent diseases, stressful situations, surgical interventions. To prevent crises of adrenal insufficiency, the dose of glucocorticosteroids should be increased 3-5 times. In urgent conditions, timely parenteral administration of hydrocortisone is important.