Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of diseases caused by congenital defects of one or more enzymes in the enzyme system for the biosynthesis of adrenocortical hormones, resulting in altered levels of hormones such as cortisol. It usually follows autosomal recessive inheritance; clinically, 21-hydroxylase deficiency is the most common, accounting for more than 90%, with an incidence of approximately 1 in 4,500 newborns, of which about 75% are salt-wasting type; the next most common is 11β-hydroxylase deficiency, accounting for about 5% to 8%, with an incidence of approximately 1 in 5,000 to 7,000 newborns; the other types are all rare.

Common Symptoms

Excessive secretion of mineralocorticoids; benign adrenal cortical...; adrenal hyperplasia; precocious puberty in females; azoospermia after puberty; adrenocortical hyperfunction; amenorrhea; intersexuality

Etiology

Almost all CYP21 mutations are the result of recombination between CYP21 and CYP21P (unequal crossing over or conversion). About 20% of mutant alleles carry deletion mutations. About 75% of mutant alleles are the result of gene conversion. In 32% of salt-wasting patients, one allele has a large deletion or conversion mutation, and 56% have a point mutation in intron 2 on one allele causing abnormal RNA splicing. In vitro experiments have confirmed that these mutations cause complete or almost complete loss of 21-hydroxylase activity. In the simple virilizing type, the most common mutant allele (35%) has a substitution mutation at amino acid codon 172 (Ile to Asn), retaining only 2% to 11% of normal 21-hydroxylase activity. The most common mutation (39%) in the non-classic type is a mutation of amino acid 281 (Val to Leu). It has been found that abnormal expression of gastric inhibitory polypeptide (GIP), arginine vasopressin (AVP) and β2-adrenergic receptors in the adrenal glands can cause AIMAH.

Treatment

Pharmacotherapy, supportive treatment

Preventive Measures

1. Newborn screening for CAH: mainly refers to screening and diagnosis of 21-OHD in newborns. The purpose is to prevent life-threatening adrenal crises and the resulting brain damage or death, to prevent misassignment of sex in female infants due to virilization of the external genitalia, and to prevent short stature and disorders of psychological and physiological development caused by excessive androgens, enabling early diagnosis and treatment before clinical symptoms appear. The newborn CAH screening method is to collect blood from the heel of every newborn infant 3 to 5 days after birth, drop it onto specially prepared filter paper, and determine the 17-OHP concentration in the dried blood spot by various detection methods such as enzyme-linked immunosorbent assay (ELISA) and fluorescence immunoassay for early diagnosis. In normal infants, 17-OHP can be greater than 90 nmol/L after birth and decreases to normal 12 to 24 hours later. The 17-OHP level has a certain relationship with birth weight; in normal full-term infants, the 17-OHP level is below 30 nmol/L; in low birth weight infants (1500 to 2700 g) it is 40 nmol/L; in very low birth weight infants (500 nmol/L indicates typical CAH, and 150 to 200 nmol/L can be seen in various types of CAH or false positives. The positive cutoff point for 17-OHP screening should still be established according to each laboratory's method and adjusted through long-term observation and experience. Positive cases require close follow-up, with confirmation through measurement of plasma cortisol, testosterone, DHEA, DHA and 17-OHP levels. 2. Prenatal diagnosis and treatment: 21-hydroxylase gene analysis should be performed for CAH probands and their parents. When the mother becomes pregnant again, at 4 to 5 weeks of gestation, oral dexamethasone 20 μg/(m²/d) (generally 1 to 1.5 mg/d) is given; at 9 to 11 weeks of gestation, chorionic villus sampling (CVS) biopsy is performed for chromosome testing, and DNA is analyzed for the CYP21B gene. If the above results indicate that the fetus is male, heterozygous or normal, dexamethasone treatment can be discontinued. If amniotic fluid testing suggests a high probability that the fetus is a female homozygous affected child, dexamethasone treatment is continued until birth.

Department of Visit

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Reminder: The above information is for health education reference only and cannot replace professional medical diagnosis. If you have related symptoms, please seek timely medical attention at a regular hospital.