Syndrome adrenogenital

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Syndrome adrenogenital

Adrenogenital syndrome is a congenital pathological condition caused by dysfunction of the adrenal cortex with excessive secretion of androgens and manifested by signs of virilization. Etiology and pathogenesis. The syndrome is caused by a deficiency of one of the enzymes necessary for the synthesis of cortisol. Cortisol deficiency stimulates the production of ACTH, which leads to hyperplasia of the adrenal cortex and excessive production of ACTH-dependent steroids, the synthesis of which is not impaired in this enzyme deficiency (mainly adrenal androgens – dehydroepiandrosterone, androstenedione and testosterone).

Genetic Aspects

    • 21-hydroxylase deficiency (*201910, EC 1.14.99.10, 6p21.3, mutations in the CYP21, CA2, CYP21P, p genes) is observed in 95% of cases of adrenogenital syndrome
    • With a moderate deficiency of the enzyme, a virilous (uncomplicated) form of the syndrome develops, in which only the symptoms of androgen excess are of importance (glucocorticoid and mineralocorticoid deficiency does not manifest itself)
    • With a complete block of the enzyme, a salt-losing (severe) form develops (Debre-Fibiger syndrome). Along with a decrease in the synthesis of cortisol, the production of aldosterone is reduced; Mineralocorticoid deficiency leads to hyponatremia, hyperkalemia, dehydration, and arterial hypotension. This form manifests itself in the first months of life, more often in boys. Without treatment, it usually ends in death. The salt-wasting form may develop as a result of deficiency of other enzymes.
    • Deficiency of 3-p-dehydrogenase (*201810, EC 1.1.1.210, 1p13.1, mutations in the HSD3B1, HSD3B2, p genes) leads to impaired synthesis of cortisol and aldosterone at the early stages of their formation. Patients develop a salt-wasting form of the disease. Due to the presence of other sources of estrogen formation, virilization in girls is poorly expressed. In boys, not only signs of hermaphroditism are observed, but also hypospadias and cryptorchidism, which indicates a violation of the synthesis of enzymes not only in the adrenal glands, but also in the testicles. Lethality is high. Synonyms: 3-p-hydroxysteroid dehydrogenase, 20-a-hydroxysteroid dehydrogenase, progesterone reductase. Catalyzed reaction: 5-a-androstan-3-p,17-(3-diol
    • NADP
    • = 17-p-hydroxy-5-a-androstan-3-one
    • NADPH (also catalyzes the conversion of 20-a-hydroxysteroids
    • Insufficiency of 18-oxidase (“124080, corticosterone methyl oxidase I, p) is manifested by an isolated violation of aldosterone synthesis with the development of a salt-losing form of the disease. Patients die in early childhood. see also
    • 11-p-hydroxylase deficiency
    • 11-p-hydroxylase deficiency (*202010, EC 1.14.15.4, 8q21, CYP11B1 gene mutations
    • CYP11B2, p) causes hyperproduction of the mineralocorticoid deoxycorticosterone, as well as adrenal androgens (hypertensive form of adrenogenital syndrome). Synonyms: steroids 11-p-monooxygenase, steroids 11-0/18-hydroxylase, 18-hydroxysteroid dehydrogenase, 18-hydroxylase). Biochemistry: 11-p-hydroxylase system in the fascicular and glomerular zones of the adrenal cortex functions separately. Moreover, 11-p- and 18-hydroxylating activities in the beam zone also function separately within the common catalytic center. 11-p- and 18-hydroxylase activities are defective in the zona fasciculata, but intact in the zona glomeruli. 18-hydroxylase, which catalyzes the conversion of corticosterone into a special metal-enzyme complex, is also called
    • corticosterone methyl oxidase type I
    • , and 18-hydroxysteroid dehydrogenase, which catalyzes the further transformation of the complex into aldosterone, is
    • corticosterone methyl oxidase type II
    • Deficiency of 20,22-desmolase (*201710, p) is manifested by impaired synthesis of cortisol, aldosterone, and androgens. This results in salt loss, glucocorticoid deficiency, and delayed sexual masculinizing development in male fetuses. The so-called. congenital lipoid hyperplasia of the adrenal cortex. Patients die in early childhood
    • Other

forms (for example, insufficiency of 17-a-hydroxylase, see Lack of P-alpha-hydroxylase) are observed much less frequently.

Clinical picture

    • The viril form is manifested mainly by an excess of androgens.
    • In girls, congenital changes in the genitals are often observed (penis-shaped clitoris, urogenital sinus, scrotum-shaped labia majora). In the postnatal period, virilization continues (male-type muscle growth, rough voice, hirsutism, amenorrhea, atrophy of the mammary glands)
    • In male infants, the consequence of an excess of androgens during fetal development is macrogenitosomia. In the postnatal period, precocious puberty begins against the background of testicular underdevelopment (spermatogenesis is absent).
    • The salt-losing form is traditionally observed in newborns and toddlers of the first year of life. It is manifested by regurgitation, vomiting, diarrhea, weight loss, arterial hypotension and convulsions. Cortisol deficiency traditionally does not have significant clinical manifestations. despite the deficiency of a particular enzyme, ACTH stimulation and adrenal hyperplasia keep cortisol levels at the lower limit of normal.
    • hypertensive form. Along with virilization in girls and macrogenitosomia in boys, persistent arterial hypertension is noted.

Diagnostics

    • Increased concentrations of adrenal androgens (testosterone, androstenedione, dehydroepiandrosterone) and cortisol precursors (17-hydroxyprogesterone) in the blood and urine
    • Increased concentrations of 17-hydroxycorticosteroids (17-OKS) and pregnanetriol (17-hydroxyprogesterone metabolite) in urine
    • Dexamethasone test. Taking dexamethasone at a dose of 2 mg 4 times a day for 2 days suppresses the production of ACTP and leads to a decrease in the daily excretion of 17-OCS by 50% or more. With tumors (androsteromas, adrenoblastomas), such a decrease is not observed.
    • In the salt-losing form, an increased content of K +, a reduced content of Na

•

Differential diagnosis is carried out with adrenal insufficiency, hermaphroditism of another origin, various types of precocious puberty, androgen-producing tumor of the adrenal glands. The salt-losing form should also be differentiated from pyloric stenosis, intestinal infections and intoxications.

Treatment:

Medical treatment. Glucocorticoids for life (destroy hyperproduction of ACTH, as well as adrenal androgens). In the sodium-deficient form, mineralocorticoid replacement therapy (fludrocortisone) may be necessary. Surgical treatment. In the first few years of life, reconstructive surgery is performed on the external genital organs of girls.

Synonyms

  • Congenital dysfunction of the adrenal cortex
  • Apert Game Syndrome
  • Crook-Apier-Halle Syndrome Reduction. 17-OX-17-hydroxycorticosteroids See also Disorders of sex differentiation of the KSD. E25 Adrenogenital disorders MIM
  • 124080 18-oxidase deficiency
  • 201710 20,22-desmolase deficiency
  • 201810 3-p-dehydrogenase deficiency
  • 201910 21-hydroxylase deficiency
  • 202010 11-p-hydroxylase deficiency