Insufficiency of 11-hydroxylase

The enzyme 11-hydroxylase also participates in the synthesis of adrenal hormones( both glucocorticoids and mineralocorticoids).The lack of the hormone cortisol is accompanied by excessive production of adrenocorticotropic hormone pituitary and male hormones( androgens).Intermediate products of synthesis of adrenal hormones, accumulating as a result in the body in an excessive amount, have mineralocorticoid activity, ie, they affect the water-salt metabolism. An increased amount of them leads to a delay in the body of sodium and water, and as a consequence of the overflow of the fluid in the bloodstream, hypertension develops.

When a child is born, signs of intra-uterine hyperproduction of androgens are noted, signs of chronic adrenal insufficiency( rapid loss of body weight, loss of appetite, regurgitation, darkening of the nipples, midline of the abdomen and external genitalia), combined with increased blood pressure resistant to antihypertensive drugs. Therefore, this form is called hypertensive. In the first year of life there may be crises of acute adrenal insufficiency( i.e., this form becomes similar in its manifestations to the salt-losing form).

The most reliable methods for detecting congenital hyperplasia of the adrenal cortex are the detection of a defective gene in the cells of patients, as well as the determination in the serum of blood and urine of intermediate products of the formation of adrenal hormones. When the anomalous structure of the external genitalia is necessary to determine the genetic sex of the child.

In order to identify the congenital dysfunction of the adrenal cortex, as well as to determine the type of enzyme, the defect of which led to the development of this disease, it is necessary to undergo a particularly thorough study of the biochemical parameters of blood serum, and in some cases urine produced in specialized endocrinology hospitals. At the same time, the entire plan of the necessary examination in each case of the disease is strictly individual and determined by the attending physician.

Treatment. With congenital dysfunction, the adrenal cortex carries out hormone replacement therapy with glucocorticoids. In the case of a salt-losing form of the disease, other hormones of the adrenal glands are also added to therapy because their formation in this organ is also impaired. This hormone is called mineralocorticoids. A glucocorticoid of choice is cortisol, available in the form of tablets. The daily dose of this drug is 15-20 mg / m2 body surface. In this case, the daily dose is divided into 2-3 doses, most of the hormone is taken in the morning. Children synthetic glucocorticoids, such as prednisolone and dexamethasone, it is better not to take, as against their background there is a growth retardation. In a number of cases, the reception of synthetic glucocorticoids in the evening or at night is justified. This allows to reduce the increased production of adrenocorticotropic hormone. The latter is a hormone of the pituitary( gland of the brain) and affects the adrenal glands, stimulating the formation of hormones, including androgens. In the case of salt forms, it is necessary to administer a drug such as cortinefine in a daily dose of 20-200 μg.

A positive effect in the treatment of hormonal drugs, namely glucocorticoids, is that all signs of the disease( symptoms) gradually disappear or become less pronounced. In addition, the growth and development of the child also improve, approaching more and more to the age norms. In addition to these data, laboratory monitoring of serum levels of hormones, as well as some other substances taking part in the exchange, is necessary.

With a saltwort crisis( acute adrenal insufficiency), prednisolone 10 mg in neonates, 25 mg in children, 50 mg in adults is injected at one time. At the same time, a 0.9% sodium chloride solution( physical solution) and 5% glucose solution are transfused in a volume of 100-200 ml / kg of body weight per day.

With late detection of the forms of congenital adrenal cortex dysfunction with the appearance of masculine traits, in persons with genetically female sex surgical procedures for the plasty of the external genital organs may be necessary. In adults, and also if the disease develops after the end of puberty, in the event of termination of growth, synthetic glucocorticoids are most often prescribed, for example, dexamethasone 0.25 mg per day. As a rule, additionally prescribed drugs that reduce the activity and reduce the effect of male hormones of the adrenal glands. Such drugs are called antiandrogen, and they include, for example, cyproterone( androkur).

In case of detection of congenital adrenal cortex dysfunction, the child should immediately start treatment of this disease( prenatal therapy) before birth. The drug of choice in this case is dexamethasone, which penetrates the placenta in an unmodified form. If the diagnosis was made at the 5th-6th week of pregnancy, the drug is prescribed 3 times a day at a dose of 0.5 mg. If it later turns out that the fetus has a female sex and it is homozygous, then the treatment continues until the end of pregnancy. Otherwise, treatment is gradually canceled.

With a simple form, the prognosis of the disease is favorable for life, and in the case of early initiation of treatment - and for normal growth and sexual development. With hypertensive form, death can occur as a result of cerebral hemorrhage, as well as the development of renal failure. The prognosis is always serious in children with a salt form. In the case of this form of illness, mortality is about 10% of all cases. The prognosis improves if the child, through proper treatment, survives to one year.

Prenatal diagnosis of congenital hyperplasia of the adrenal cortex due to the deficiency of the enzyme 21-hydroxylase is carried out in two stages. The first study is carried out at 9-10 weeks of pregnancy by determining the sex of the fetus and conducting a special genetic study of the material obtained with chorion biopsy. At the 13-16 week of pregnancy, the level of 17-hydroxyprogesterone in the amniotic fluid is examined. The indication for prenatal diagnosis is the presence in the given marriage of a child with a proven deficiency of 21-hydroxylase, the marriage of two known carriers of a defective gene or a patient with a known carrier. A high level of 17-hydroxyprogesterone in the amniotic fluid indicates the presence of a 21-hydroxylase enzyme deficiency in the fetus. The appointment of a hormonal drug dexamethasone to such women from 5-6 weeks of gestation and until the onset of labor can prevent or significantly reduce the intensity of the appearance of male characteristics in female fetuses. There is also the possibility of prenatal diagnosis of the deficiency of the enzyme 11-hydroxylase.