Congenital adrenal hyperplasia


Introduction to congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of diseases caused by changes in hormone levels such as cortisol due to congenital defects in one or several enzymes in the adrenocortical hormone biosynthetic enzyme system. Often autosomal recessive inheritance. Clinically, 21-hydroxylase deficiency is the most common, accounting for more than 90%. The incidence rate is about 1/4500 newborns, of which about 75% is salt-loss type, followed by 11-hydroxylase deficiency. It accounts for 5% to 8%, and its incidence rate is about 1/5000 to 7000 newborns. Other types are rare.

basic knowledge

The proportion of illness: 0.02%

Susceptible people: children

Mode of infection: non-infectious

Complications: hypospadias cryptorchidism female pseudohermaphroditism


Causes of congenital adrenal hyperplasia

Gene mutation (90%)

Almost all CYP21 mutations are the result of recombination between CYP21 and CYP21P (unequal exchange or conversion). Approximately 20% of the mutant alleles carry deletion mutations. Approximately 75% of the mutant alleles are the result of gene conversion. In 32% of patients with salt loss, there is a large fragment deletion or mutation in one allele, and 56% of point mutations in intron 2 on one allele cause RNA splicing abnormalities. These mutations were confirmed in vitro to completely or almost completely lose 21-hydroxylase activity. In the simple male type, the most common mutant allele (35%) is the substitution mutation of the amino acid codon 172 (Ile becomes Asn), and only retains 2% to 11% of the activity of normal 21-hydroxylase. The most common (39%) mutation in the non-classical type is the mutation of amino acid 281 (Val becomes Leu). Abnormal expression of gastric inhibitory peptide (GIP), arginine vasopressin (AVP), and 2-adrenergic receptor in the adrenal gland has been found to cause AIMAH.


Congenital adrenal hyperplasia prevention

1. Screening for neonatal CAH: mainly refers to the screening diagnosis of neonatal 21-OHD. The purpose is to prevent life-threatening adrenal crisis and the resulting brain injury or death, prevent female children from being wronged by gender due to masculinization of external genitalia, prevent shortness, and psychological development after excessive androgen deficiency. Obstacles, so that children get early diagnosis and treatment before clinical symptoms appear.

The newborn CAH screening method is to take blood from the heel and drop it on a special filter paper for 3 to 5 days after birth. By using various detection methods, such as enzyme-linked immunosorbent assay (ELISA), The 17-OHP concentration in the filter paper is measured by fluorescence immunoassay for early diagnosis. 17-OHP of normal infants can be >90nmol/L after birth, and will fall to normal after 12-24h. The level of 17-OHP has a certain relationship with birth weight. The normal 17-OHP level is below 30nmol/L, the low birth weight (15002700g) is 40nmol/L, and the very low body weight (500nmol/L is typical CAH, 150~200nmol/L can be seen in various types of CAH or false positives. The positive cutting point of 17-OHP screening should still be determined according to each laboratory method, and adjusted by long-term observation and experience. Positive cases need close follow-up The diagnosis was confirmed by measuring plasma cortisol, testosterone, DHEA, DHA and 17-OHP levels.

2. Prenatal diagnosis and treatment: 21 hydroxylase gene analysis should be performed on CAH patients and parents. When the mother is pregnant again, oral dexamethasone 20g / (m2 / d) (generally 1 ~ 1.5mg / d) at 4 to 5 weeks of pregnancy, chorionic membranous (CVS) biopsy at 9 to 11 weeks of pregnancy Chromosome detection, DNA analysis of CYP21B gene, such as the above results suggest that the fetus is male, heterozygous or normal fetus, can be discontinued dexamethasone treatment. When the amniotic fluid test indicates that the fetus is likely to be a female homozygous child, then dexamethasone is treated until the birth of the fetus.


Congenital adrenal hyperplasia complications Complications hypospadias cryptorchidism female pseudohermaphroditism

Congenital defects of certain adrenal enzymes lead to abnormal steroidogenesis, females cause pseudohermaphroditism, male genitalia are large, enzyme defects are accompanied by excessive androgen products in the fetal uterus, in female Müllerian catheter structures (ie ovary, uterus) And vagina) will develop normally, and excessive androgen exerts its masculinizing effect in the genitourinary and reproductive nodules, so that the vagina and urethra are connected, the hypertrophic clitoris is low and open, the labia is often hypertrophied, and the severe urethra In the rupture and cryptorchidism, the adrenal cortex causes varying degrees of cortisol deficiency due to the secretion of most anabolic male steroids.


Symptoms of congenital adrenal hyperplasia common symptoms amenorrhea adrenal hyperfunction hyperplasia adrenal hyperplasia female precocious adrenal cortical benign ... high testosterone bilateral adrenal hyperplasia of hereditary hypersensitivity hypertension after puberty without semen

Increased ACTH secretion causes bilateral adrenal hyperplasia, and the proliferating cortex continues to synthesize androgen and hypertensive mineral corticosteroids in large amounts.

The lack of 20-22 carbon chain enzymes leads to rare congenital fatty adrenal hyperplasia, often with complete barriers to steroidogenesis. If there is not enough replacement therapy, the baby will die early.

The lack of 3&beta-hydroxysteroid dehydrogenase isomerase leads to synthetic barriers to progesterone, aldosterone and cortisol, and dehydroepiandrosterone is overproduced. The unusual syndrome is characterized by hypotension, hypoglycemia and male pseudo sex. Malformation, women are uncommon hairy, with varying levels of melanin.

Insufficient or lack of 21-hydroxylase prevents the conversion of 17-carboxyprogesterone to cortisol, which is more common in two forms:

A variety of sodium is lost, aldosterone is low or absent; common is non-sodium loss, hairy, masculine, hypotension and pigmentation are common.

17 & alpha-hydroxylase deficiency, most commonly seen in female patients, some to adulthood with low levels of cortisol, ACTH compensatory increase, primary amenorrhea, sexual naive, few male pseudohermaphroditism, salt corticosteroid secretion More causes high blood pressure, mainly 11-deoxycorticosterone.

11&beta-hydroxylase deficiency impedes the formation of cortisol and corticosterone, ACTH release is too high, resulting in deep melanin deposition, high blood pressure due to excessive secretion of 11-deoxycorticosterone, no obvious abnormalities.

Lack of 18-hydroxysteroid dehydrogenase, rare skin disease, caused by the specific block of the last step of aldosterone biosynthesis, so patients with more urinary sodium loss, causing dehydration and hypotension.

After puberty, masculine manifestations such as hairy and amenorrhea are rarely found, and masculinity occurs by chance in middle age. This acquired abnormality of the adrenal mild enzyme is called benign masculinization of the adrenal cortex.

The newborn genital genitalia has severe hypospadias and cryptorchidism. The boy is mostly normal at birth. There are excessive androgen in the fetus in the uterus, so there is obvious abnormality.

Untreated patients have hairy, muscular, amenorrhea and breast development. Male patients have abnormally large reproductive organs. Too much androgen inhibits the secretion of gonadotropins, causing testicular atrophy. In extremely rare cases, the adrenal glands have hyperplasia in the testes. Residual cortex will make the testicles enlarge and harden. The majority of patients have no semen after puberty. Because of adrenal hyperplasia, the height of the patient increases suddenly from 3 to 8 years old, so much higher than that of the same age, about 9 to 10 years old. Hormone-induced early fusion of the epiphysis causes the growth to stop, and the patient is shorter after adulthood. Both men and women have provocative behaviors and increased sexual desire, which leads to social problems and disciplinary problems, especially in some boys.


Examination of congenital adrenal hyperplasia

Urinary 17-keto alcohol levels are higher than normal age of the same sex, urinary progesterone levels increased early (this is more sensitive than urine 17-KS levels, because progesterone is a precursor of androgen), blood Increased levels of 17-hydroxyprogesterone are the most sensitive indicators. They are suitable for children. Chromosome examination is normal. X-ray examination will reveal early bone age. Lateral urethral cystography will show vaginal, urethra and bladder. CT scan can be highly hyperplastic. Adrenal gland, urethroscopic can see the vagina opening in the posterior wall of the urethra, can also enter the vagina and see the uterus.


Diagnosis and diagnosis of congenital adrenal hyperplasia

Many congenital malformations affecting external genital development resemble adrenal syndrome, including: (1) severe hypospadias and cryptorchidism, and (2) non-adrenal female pseudohermaphroditism (due to excessive androgen use during pregnancy) Or progesterone drugs), (3) male pseudohermaphroditism, (4) true hermaphroditism, these children are not ahead of any hormonal abnormalities, bone age and maturity.

In the differential diagnosis:

1. Mainly identified with 11-hydroxylase deficiency (11-OHD) 11 hydroxylase (P450c11) deficiency is the second most common type of CAH, accounting for only 5% to 8%. The incidence rate in the population is 1/10,000.

When the CYP11B1 gene is defective, it causes 11-OHD-induced CAH, adrenal 11-deoxycortisol (S) cannot be converted to cortisol (F), and deoxycorticosterone (DOC) cannot be converted to corticosterone (S), which ultimately cannot be synthesized. Aldo, causing increased blood DOC and S concentrations, DOC is also a strong sodium-sodium hormone, can cause high blood sodium, hypokalemia, hypertension, alkalosis, through feedback, renin-angiotensin is inhibited, making Aldo Reduced synthesis, decreased levels of blood PRA and Aldo. As cortisol synthesis is blocked, symptoms of adrenal insufficiency can occur, ACTH levels increase, and levels of androgen, DHEA, 4-A, testosterone, and urinary 17-KS increase, and high androgen symptoms and characteristics similar to 21-OHD appear.

2. The lack of other various enzymes leads to the identification of CAH.

3. Loss of salt 21-OHD is differentiated from chronic adrenal insufficiency (hypoadrenocorticism, Addison disease). Addison disease has loss of salt, reduction of cortisol, decreased sex hormones, no masculine symptoms, and 17-OHP is normal.

4. Simple masculine CAH and the following diseases

(1) Males should be identified with true precocious puberty: the morphology of the external genitalia is similar, but the latter testicular and penis increase at the same time, close to puberty, 17-KS and testosterone reach puberty level, but 17-OHP is normal, FSH, LH increase .

(2) Female CAH needs to be differentiated from true hermaphroditism. Although the external genitalia can be masculine, the blood levels of 17-KS and testosterone can be normal.

(3) Adrenal male tumors: After birth, male symptoms gradually develop, blood androgen levels can be increased, 17-OHP is normal, and one adrenal mass can be found by B-ultrasound or CT.

5. Female atypical 21-OHD and polycystic ovary syndrome identified the latter occurred in women of childbearing age, with high androgenic symptoms and signs, and insulin resistance, B-ultrasound showed multiple ovarian cysts.

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