Congenital Adrenal Hyperplasia, Which Is Caused By A Defect Of The 11-Hydroxylase

The 21-hydroxylase deficiency (CYP21A2) gives poor conversion of adrenal hormone precursors to cortisol and in some cases to aldosterone. This sometimes leads to severe hyponatremia and hyperkalemia. Piled hormone precursors are derived in androgen production, resulting in the virilization. The diagnosis is made by the determination of cortisol, its precursors and the adrenal androgens, sometimes after ACTH stimulation. The treatment is performed with glucocorticoids and if necessary a mineralocorticoid. In women with intersex genitals surgical intervention is required.

90% of all cases of a congenital adrenal hyperplasia are characterized by a 21-hydroxylase deficiency causes (overview of congenital adrenal hyperplasia). The incidence varies between 1 / 10,000 and 1 / 15,000 live births. The severity of the disease depends on the specific CYP21A2 mutation and the degree of enzyme deficiency. The lack blocks the conversion of 17-hydroxyprogesterone 11-deoxycortisol, a precursor of cortisol and the conversion of progesterone in deoxycorticosterone, a precursor of aldosterone, completely or partially. Because cortisol is decreased, the ACTH levels increase, which stimulates the adrenal cortex, which in turn accumulates cortisol precursor (z. B. 17-hydroxyprogesterone) and the androgen dehydroepiandrosterone (DHEA) and androstenedione are produced excessively. Aldosterone deficiency can lead to salt loss hyponatremia (hyponatremia) and hyperkalemia (hyperkalemia).

The 21-hydroxylase deficiency (CYP21A2) gives poor conversion of adrenal hormone precursors to cortisol and in some cases to aldosterone. This sometimes leads to severe hyponatremia and hyperkalemia. Piled hormone precursors are derived in androgen production, resulting in the virilization. The diagnosis is made by the determination of cortisol, its precursors and the adrenal androgens, sometimes after ACTH stimulation. The treatment is performed with glucocorticoids and if necessary a mineralocorticoid. In women with intersex genitals surgical intervention is required. 90% of all cases of a congenital adrenal hyperplasia are characterized by a 21-hydroxylase deficiency causes (overview of congenital adrenal hyperplasia). The incidence varies between 1 / 10,000 and 1 / 15,000 live births. The severity of the disease depends on the specific CYP21A2 mutation and the degree of enzyme deficiency. The lack blocks the conversion of 17-hydroxyprogesterone 11-deoxycortisol, a precursor of cortisol and the conversion of progesterone in deoxycorticosterone, a precursor of aldosterone, completely or partially. Because cortisol is decreased, the ACTH levels increase, which stimulates the adrenal cortex, which in turn accumulates cortisol precursor (z. B. 17-hydroxyprogesterone) and the androgen dehydroepiandrosterone (DHEA) and androstenedione are produced excessively. Aldosterone deficiency can lead to salt loss hyponatremia (hyponatremia) and hyperkalemia (hyperkalemia). Synthesis of adrenal hormones. * Enzymes that are stimulated by ACTH. 11? = 11?-hydroxylase (P-450c11); 17? = 17?-hydroxylase (P-450c17); 17,20 = 17,20 lyase (P-450c17); 18 = aldosterone synthase (P-450aldo); 21 = 21-hydroxylase (P-450c21); DHEA = dehydroepiandrosterone; DHEAS = DHEA-sulphate; 3?-HSD = 3?-hydroxysteroid dehydrogenase (3?2-HSD); 17?-HSD = 17?-hydroxysteroid dehydrogenase (17?-HSD); SCC = Side Chain Cleavage (P-450scc); SL = sulfotransferase (SULT1A1, SULT1E1). Classic 21-hydroxylase deficiency classic 21-hydroxylase deficiency can be divided into two forms: salt loss Simple virilization the androgen levels of the adrenal glands are increased in both forms, resulting in virilization. The salt-wasting form is the most severe and is responsible for 70% of cases of classical 21-hydroxylase; there is a complete lack of enzyme activity, which leads to very low levels of cortisol and aldosterone. Because minimal Aldosterone is secreted, salt is lost, resulting in hyponatremia, hyperkalemia and increased plasma renin activity. In simple Virilisierungsform cortisol synthesis is disturbed, which leads to increased androgen activity, but it is sufficient enzyme activity before to get a normal or only slightly decreased aldosterone upright. Non-classical 21-hydroxylase deficiency non-classical 21-hydroxylase deficiency is more common than classical 21-hydroxylase deficiency. The incidence ranges from 1/1000 to 1/2000 live births in the fair-skinned population (0.1 to 0.2%) to 1 to 2% in certain ethnic groups (eg. B. Ashkenazi Jews). Non-classical 21-hydroxylase deficiency causes a less severe form of the disease in which 20 to 50% of the 21-hydroxylase activity present (as compared to 0 to 5% of the activity in the classical 21-hydroxylase deficiency). The loss of salt is missing because the aldosterone and cortisol levels are normal, but the androgen levels of the adrenal glands is slightly increased, resulting in a slight androgen excess in childhood or adulthood. Symptoms and complaints The salt-loss syndrome caused next to hyponatremia (sometimes severe), hyperkalemia and hypotension also virilization. If undiagnosed or untreated, it can escalate to life-threatening adrenal crisis with vomiting, hypoglycemia, hypovolemia and shock. With both forms of classical 21-hydroxylase deficiency have female newborn intersexual external genitalia with enlargement of the clitoris, bonding of the labia majora and an urogenital sinus instead a significant urethral or vaginal opening. Male infants have a normal genital development, which can delay the diagnosis of salt-wasting form in the rule; Affected boys are often only identified by routine newborn screening. If it is not detected with newborn screening, boys are eventually diagnosed with the simple Virilisierungsform after a few years if they show signs of a Androgenexzesses. Among the signs of Androgenexzesses include an early onset of pubic hair and growth acceleration in both sexes, enlargement of the clitoris in girls and penis enlargement and former voice broke in boys. Children with non-classic 21-hydroxylase deficiency have no symptoms at birth and make not usually before childhood or adolescence before. Affected girls can have an early development of pubic hair, advanced bone age, hirsutism, oligomenorrhea and / or acne; these symptoms may be the manifestations of the syndrome resembling polycystic ovary (polycystic ovarian syndrome (PCOS)). Affected boys may have an early development of pubic hair, growth acceleration and an advanced bone age. They may have a fusion of the labia majora and anovulatory cycles or amenorrhea. The affected women, especially those with a salt wasting syndrome that fertility may be compromised when they reach adulthood. Some men with a salt wasting syndrome are fertile as adults, but others may develop a testicular adrenal rest tumor (benign intratesticular mass consisting of adrenal tissue from chronic ACTH stimulation hypertrophied), Leydig cells, decreased testosterone levels and impaired spermatogenesis. Most affected men without salt wasting syndrome and untreated fertile. In some impaired spermatogenesis is present. Diagnostic blood test may ACTH stimulation test may genotyping A routine newborn screening usually involves the measurement of serum levels of 17-hydroxyprogesterone. If the levels are elevated, the diagnosis by determining the blood levels of cortisol and DHEA and androstenedione high levels must be confirmed. Rarely, the diagnosis is uncertain once; then the levels of these hormones must be measured before and after ACTH administration (ACTH or Cosyntropintest). In patients who develop symptoms later, the ACTH test can help sometimes but genetic tests are necessary. Children with the salt-wasting form have hyponatremia and hyperkalemia; low levels of desoxycorticosterone, corticosterone and aldosterone and high renin levels. Prenatal screening and appropriate diagnosis and experimental treatment are possible. In high risk patients, the CYP21 genes are investigated (for. Example, if the fetus had an affected sibling). The carrier status (heterozygosity) can be determined in children and adults. Therapy with corticosteroids mineralocorticoid replacement (salt-wasting form) may reconstructive surgery in case of adrenal crisis in infants is a treatment with iv Liquid urgently needed. The stress dose of hydrocortisone (100 mg / m2 per day) is continuous with i.v. Fluid provided when the salt form of loss is believed to prevent adrenal crisis; the dose is reduced over weeks to physiological maintenance doses. Clinical Calculator: body surface (Du Bois Method) The maintenance medication consisting of corticosteroids as replacement for the missing steroids (typically hydrocortisone 3.5-5 mg / m 2 3 times a day, with a daily Gedamtdosis of typically ? 20 mg / m2). Post pubertal adolescents and adults with prednisone 5-7.5 mg po 1 times a day, or 2.5 to 3.75 mg 2 times a day, or with dexamethasone 0.25-0.5 mg of 1-times daily or 0.125-0.25 mg be treated 2 times a day. Cortisone acetate 18-36 mg / m2 i.m. every 3 days may be given to infants when oral therapy is not reliable. For 12 months, the response is (> 12 months in children) controls to therapy every 3 months (in infants) and every 3-4 months. Overdose leads to an iatrogenic Cushing’s syndrome (Cushing’s syndrome) with truncal obesity, reduced growth and delayed skeletal growth. Underdosing leads to an increase of ACTH, with resultant hyperandrogenism that causes a virilization and a growth spurt on the normal values ??of children, and finally closes the growth plates at an early stage, resulting in a short stature. In the quarter to half year clinical monitoring the serum levels of 17-hydroxyprogesterone and androstenedione as well as the rate of growth and skeletal maturation are determined. As maintenance medication in salt wasting syndrome mineralocorticoids are given in order to achieve homeostasis of sodium and potassium in addition to corticosteroids. Oral fludrocortisone (0.1 mg once a day, between 0.05 and 0.3 mg) is administered, if there is a loss of salt. Babies need until the first year of life mostly salt substitution. Close monitoring this therapy is vital. In affected girls possibly a reduction surgery of the clitoris and a reconstruction of the vagina must be performed. Often another surgery in adulthood is required. With proper care and attention with regard to psychosocial concerns a normal sex life can be guided and fertility expected. In the prenatal treatment of the mother is given a corticosteroid (dexamethasone) to suppress the fetal pituitary secretion of ACTH. In this way, the masculinization of female fetuses affected is reduced or prevented. The treatment is experimental, but pregnancy must begin in the first weeks. The treatment of non-classical 21-hydroxylase deficiency depends on the symptoms. If he is asymptomatic, no treatment is necessary. If he is symptomatic corticosteroid treatment of those are for the classic 21-hydroxylase deficiency, but lower doses similar often effective. A mineralocorticoid replacement is not required. Key points Children with 21-hydroxylase deficiency have varying degrees of Androgenexzess and about 70% have a salt-wasting form, caused by aldosterone deficiency. In girls, the Androgenexzess usually manifested with intersexual external genitalia (e.g., enlargement of the clitoris, bonding of the labia majora, a urogenital sinus instead a significant urethral or vaginal opening.); later in their lives they may have hirsutism, oligomenorrhea and acne. In boys, the Androgenexzess is not obvious or perhaps it manifests in childhood with an increased growth rate and early signs of puberty. In both sexes, the salt loss hyponatremia and hyperkalemia caused. The diagnosis is made with steroid hormone levels and sometimes ACTH stimulation and / or genotyping. The treatment is performed with the replacement of corticosteroids and sometimes mineralocorticoids; Girls may require reconstructive surgery.

Health Life Media Team

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