Adrenogenital syndrome in children

Congenital dysfunction of the adrenal cortex (synonym: adrenogenital syndrome in children) includes a group of hereditary enzymopathies. Each of the enzymopathies is based on a genetically determined defect of an enzyme involved in steroidogenesis.

Defects of five enzymes involved in the synthesis of gluco- and mineralocorticoids are described, which results in the formation of one or another variant of adrenogenital syndrome in children. 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.
• E25.8 Other adrenogenital disorders.
• E25.9 Adrenogenital disorder, unspecified.

What causes adrenogenital syndrome in children?

In 90% of cases, a 21-hydroxylase defect is observed, which can be caused by various mutations of the CYP21 gene encoding this enzyme. Dozens of CYP21 mutations leading to the P450c21 defect have been described. There is also a point mutation with partial 21-hydroxylase activity. 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 is not involved in the synthesis of sex steroids. Disruption of cortisol synthesis stimulates ACTH production, which leads to hyperplasia of the adrenal cortex. In this case, 17-OH-progesterone, a precursor of cortisol, accumulates. Excess 17-OH-progesterone is converted into androgens. Adrenal androgens lead to virilization of the external genitalia in the female fetus - a girl with false female hermaphroditism is born. In boys, hyperandrogenemia determines the premature appearance of secondary sexual characteristics (premature sexual development syndrome).

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

The non-classical form of 21-hydroxylase deficiency manifests in pre- and pubertal age as adrenarche, moderate hirsutism, and menstrual irregularities in girls. Moderate to mild virilization is the result of point mutations V281L and P30L.

Symptoms of adrenogenital syndrome in children

In the classic virile form of adrenogenital syndrome in children, the external genitalia of the girl are formed according to the heterosexual type - the clitoris is hypertrophied, the labia majora resemble the scrotum, the vagina and urethra are represented by the urogenital sinus. In newborn boys, no obvious disorders can be detected. From 2-4 years old, children of both sexes begin to show other symptoms of adrenogenital syndrome in children, that is, androgenization: axillary and pubic hair growth is formed, skeletal muscles develop, the voice becomes coarser, the figure becomes masculinized, and acne appears on the face and body. In girls, the mammary glands do not grow, and menstruation does not occur. At the same time, skeletal differentiation accelerates, and the growth zones close prematurely, which causes short stature.

In the case of the salt-wasting form of 21-hydroxylase deficiency, in addition to the symptoms described above, signs of adrenal insufficiency are noted in children from the first days of life. Regurgitation appears first, then vomiting, and loose stools are possible. The child quickly loses weight, symptoms of dehydration and microcirculation disorders develop, blood pressure decreases, tachycardia begins, and cardiac arrest is possible due to hyperkalemia.

The non-classical form of adrenogenital syndrome in children is characterized by the early appearance of secondary hair growth, accelerated growth and differentiation of the skeleton. In pubertal girls, moderate signs of hirsutism, menstrual irregularities, and the formation of secondary polycystic ovary disease are possible.

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

Diagnosis of adrenogenital syndrome in children

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Laboratory diagnostics of adrenogenital syndrome in children

• All children with abnormal structure of the external genitalia, including boys with bilateral abdominal cryptorchidism, are recommended to undergo sex chromatin determination and karyotype examination.
• From the first days of life, an increased content of 17-OH-progesterone is detected in the patient's blood serum. It is possible to conduct a screening test in newborns on the 2nd-5th day of life - 17-OH-progesterone is increased several times.
• Salt wasting syndrome is characterized by hyperkalemia, hyponatremia, and hypochloremia.
• Increased urinary excretion of 17-ketosteroids (androgen metabolites).

Instrumental diagnostics of adrenogenital syndrome in children

• The bone age according to the radiograph of the wrist joints is ahead of the passport age.
• During ultrasound examination, girls' uterus and ovaries are detected.

Differential diagnosis of adrenogenital syndrome in children

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

In older children, symptoms of hyperandrogenemia should be considered for androgen-producing tumors of the adrenal glands or gonads.

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Treatment of adrenogenital syndrome in children

Drug treatment of adrenogenital syndrome in children

The virile 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 is divided into 2-3 doses. Its doses are distributed evenly throughout the day. On average, the daily dose of prednisolone is 4-10 mg. This amount of the drug suppresses excess production of androgens without causing side effects.

Treatment of the salt-wasting form of adrenogenital syndrome in children with adrenal insufficiency crisis is carried out in the same way as treatment of acute adrenal insufficiency - by drip administration of isotonic sodium chloride and glucose solution, 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 is water-soluble hydrocortisone (solucortef). When the condition stabilizes, hydrocortisone injections are gradually replaced by hydrocortisone tablets, and if necessary, a mineralocorticoid is added - fludrocortisone (2.5-10.0 mcg per day).

Surgical treatment of adrenogenital syndrome in children

Girls aged 4-6 undergo surgical correction of the external genitalia.

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

Prognosis of adrenogenital syndrome in children

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