Congenital hyperplasia of the adrenal glands. Deficiency 21 hydroxylase symptoms, treatment

Congenital adrenal hyperplasia

21 hydroxylase deficiency symptoms, treatment

Congenital adrenal hyperplasia

 

 

Congenital adrenal hyperplasia is a group of genetic disorders, each of which is characterized by a violation of the synthesis of cortisol, aldosterone, or both.

 

In various forms of congenital adrenal hyperplasia due to an autosomal recessive genetic defect in one of the adrenal enzymes that are involved in the synthesis of steroid hormones from cholesterol, the synthesis of cortisol, aldosterone, or both of them is disturbed. The enzyme may be absent or its level may be reduced, while the synthesis of cortisol, aldosterone, or both of them is partially or completely disrupted. In forms with a complete or partial decrease in the synthesis of cortisol, the secretion of ACTH, which is normally suppressed by cortisole, is significantly increased.With the most common forms, the deficiency of 21-hydroxylase and 11beta-hydroxylase precursors accumulate above the level of the enzyme block and, bypassing it, are converted into adrenal androgens. Subsequent excessive secretion of androgens leads to the development of varying degrees of virilization of the external genital organs in female fetuses; external genitals of male fetuses are usually formed correctly, without visible defects. In some less common forms in violation of other enzymes, the block of the enzyme disrupts the synthesis of androgens. As a result, virilization of male fetuses is insufficient, and defects of the female fetus are not detected.

 

21 hydroxylase deficiency

 

 

A deficiency of 21-hydroxylase causes defective conversion of adrenal precursors to cortisol, and in some cases to aldosterone, which leads to virilization and sometimes severe hypona-triemia and hyperkalemia. Diagnosis is based on measuring the level of cortisol, its precursors and adrenal androgens, sometimes after the administration of ACTH. Treatment consists of prescribing glucocorticosteroids plus, if necessary,mineralocorticoids, as well as in some female patients with male-type external genital organs performing surgical reconstruction.

 

A 21-hydroxylase deficiency causes 90% of all cases of congenital adrenal hyperplasia. The incidence is between 1 in 10,000 and 1 in 15,000 live births. A deficiency of this enzyme completely or partially blocks the conversion of adrenal precursors into cortisol and aldosterone, leading to an increase in the levels of progesterone, 17-hydroxyprogesterone, dehydroepi-androsterone and androstenedione. The level of deoxycorticosterone, desox-sicortisol, cortisol and aldosterone in the plasma is low or not determined.

 

The total deficiency of 21-hydroxylase, the salt-losing form, amounts to 70% of all cases of 21-hydroxylase deficiency. The salt-loss form is the most severe form of 21-hydroxylase deficiency; it does not produce aldosterone, and salt is lost, leading to hyponatremia, hyperkalemia, and an increase in plasma renin activity. Partial deficiency of 21-hydroxylase causes a less serious lesion, a non-solitary form, in which the aldosterone level is normal or only slightly reduced.

 

Lack of 21 hydroxylase - symptoms and signs

 

 

In the case of a solitary form, hyponatremia, giperkaliemia and hypotension, as well as virilization, develop. If the disease is not diagnosed and treatment is not carried out, this form can lead to a life-threatening adrenal crisis with vomiting, diarrhea, hypoglycemia, hypovolemia, and shock.

 

In newborn girls with a loss-forming form, the vaguenously formed external genitalia will be marked with an increase in the clitoris, the merging of the labia majora, and the presence of the urogenital sinus, rather than the independent openings of the urethra and vagina. Boys usually have a normal formation of floor-sex half bodies. With a significantly less pronounced enzyme deficiency in newborns, there are mild signs of virilization, or these signs are absent, however, an excess of androgens is manifested later by the early appearance of pubic hair and an increase in growth rate in children of both sexes, an increase in the clitoris in girls and an increase in penis and earlier voice changes in boys .

 

In girls, especially when the form is solitary, when they become adults, reproductive function may be impaired; they may have fusion of the labia and anovulatory cycles or amenorrhea.In some boys, when they grow up, fertility is not impaired, however, in some, dysfunction of Leydig cells, a decrease in testosterone levels and impaired spermatogenesis may occur. Most boys with a non-shedding form, even if left untreated, remain fertile, but some are impaired spermatogenesis. In patients with non-solitary forms, normal blood pressure is noted.

 

Deficiency 21 hydroxylases - diagnosis

 

 

Prenatal screening and diagnosis are possible; if the risk is high, the analysis of the CYP21 genes is carried out. The status of the carrier can be determined in children and adults.

 

In neonates, the serum level of 17-hydroxyprogesterone is measured in a blood sample dried on a filter paper when screening newborns. If the level is higher than the age norm, the diagnosis should be confirmed by detecting low levels of deocicortisol, cortisol, deoxycorticosterone, corticosterone, progesterone and 17-hydroxyprogesterone, as well as determining high levels of DHEA and androstenedione measured in the newborn's whole blood. Rarely, if the diagnosis is unclear, the levels of these hormones should be measured before and 60 minutes after the administration of ACTH.In patients with later onset of symptoms, a stimulation test with ACTH may help, but a genotype study may be required. In children with a salt-losing form, the levels of deoxy-corticosterone, corticosterone and aldo-sterone are lowered, and the level of renin is high. The level of metabolites of the precursors of cortisol in the urine and the predecessors of androgens is also high, but it is rarely necessary to study it for diagnosis.

 

21 hydroxylase deficiency - treatment

 

 

With the adrenal crisis, emergency therapy with intravenous fluid administration is necessary. Stressful doses of hydrocortisone [100 mg /] are administered as a continuous infusion; the dose is reduced after a few weeks to a more physiological replacement dose. Stressful doses of hydrocortisone are also used to prevent the development of the adrenal crisis when suspicion of the salt-losing form of ACS.

 

Maintenance treatment is carried out with glucocorticoids as a replacement therapy for steroid deficiency. Dexamethasone is used only in adolescents after puberty and in adults. Cortisone acetate at 18-36 mg / m intramuscularly every 3 days can be used in young children, if there is any doubt in the assimilation of oral forms.The response to treatment is monitored in children up to a year every 3 months, in children older than a year - every 3-4 months. Excessive intake of glucocorticoids leads to the development of iatrogenic Cushing's disease, causing obesity, growth retardation, and later maturation of the skeleton. Insufficient treatment leads to the inability to suppress the secretion of ACTH with the subsequent development of hyperandrogenism leading to virilization and increased growth rate in children, as well as eventually to the premature termination of growth and short stature. Monitoring includes the measurement of 17-hydroxyproges-theron and DHEA or androstenedione, as well as an assessment of growth rate and bone age annually.

 

Supportive treatment for salt-losing form in addition to gluco-corticoids includes replacement therapy with mineralocorticoid to restore sodium and potassium homeostasis. Fludrokortizon inside appoint, if loss of salt develops. Children of the first years of life often require additional oral intake for about a year. It is extremely important to frequently monitor the condition of the child during treatment.

 

Female babies may require reconstructive surgery with reduction clitoroplasty and formation of the vaginal opening.Often in the future, when a child grows up, he needs surgery, but with adequate treatment and attention to psychosexual problems, we can expect him to have a normal sex life and fertility.

 

For treatment during the prenatal period, glucocorticoids are used, which are prescribed to the mother in order to suppress the secretion of ACTH by the fetal pituitary and thus reduce or prevent masculinization in the female fetus. Treatment that is experimental should begin after the first few weeks of gestation.

 

11 beta hydroxylase deficiency

 

 

With a deficiency of 11 beta-hydroxylase, defective conversion of adrenal precursors occurs, which leads to virilization, hypernatremia, hypokalemia and hypertension. Diagnosis is based on measuring the level of cortisol, its precursors, adrenal androgens, and sometimes the definition of 11-deoxycortisol and 11-deoxycorticosterone after administration of ACTH. Treatment is carried out by glucocorticoids.

 

11beta-hydroxylase deficiency occurs in approximately 5% of all cases of congenital adrenal hyperplasia.The formation of cortisol from 11-deoxycortisol and corticosterone from 11-deoxycorticosterone is partially blocked, which leads to an increase in the level of ACTH and hyperproduction of 11-deoxycortisol, 11-deoxycorticosterone and androgens in the adrenal glands.

 

11 beta-hydroxylase deficiency - symptoms and signs

 

 

In newborn girls, there may be indistinctly shaped genitalia, including an increase in the clitoris, the fusion of the labia, and the urogenital sinus. Newborn boys usually look normal, but some have an enlarged penis. In some children, clinical manifestations appear later and include early sexual development or in female patients irregular menstruation and hirsutism.

 

Deficiency 11 beta-hydroxylase - diagnosis and treatment

 

 

Prenatal diagnosis is not performed. Diagnosis is based on the determination of elevated 11-deoxycortisol, 11-deoxycorticosterone, adrenal androgens and renin in plasma; levels of tetrahydro-11-deoxycortisol, tetrahydro-11-deoxycorticosterone, 17-hydroxycorticosteroids, and 17-ketosteroids in the urine.If the diagnosis is unclear, the level of 11-deoxycortisol and 11-deoxycorticosterone is determined before and 60 minutes after stimulation of ACTH. In adolescents, the basal level in plasma can be normal, so it is recommended to perform a stimulation test with ACTH.

 

Treatment is carried out with hydrocortisone 5-8 mg / m23 times a day to replace absent or reduced cortisol and, consequently, reduce the secretion of ACTH and reduce the level of 11-deoxycorticosterone and adrenal androgens to normal values. The appointment of a mineralocorticosteroid to restore sodium and potassium homeostasis is usually not required, but may be needed in newborns or during severe stress. The response to treatment should be monitored, as a rule, for this purpose they use the measurement of the level of 11-desoxy-cortisol, DHEA and androstenedione in serum, as well as an assessment of the growth rate and bone age. Blood pressure should be measured in patients with hypertension.

 

Female babies may require reconstructive surgery with reduction clitoroplasty and formation of the vaginal opening. Often later, when a child grows up,he needs surgery, but with adequate treatment and attention to psychosexual problems, we can expect him to have a normal sex life and fertility.


Date: 09.10.2018, 12:37 / Views: 81562

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