Congenital adrenocortical hyperplasia (CAH) is a group of autosomal recessive disorders caused by enzyme defects in the adrenocortical hormone synthesis pathway, with an incidence of 1/16,000 to 1/20,000 in newborns. Common enzyme deficiencies include 21-hydroxylase, 11β-hydroxylase, 3β-steroid dehydrogenase, 17α-hydroxylase deficiency, etc. Among them, steroid 21-hydroxylase deficiency is the most common, and more than 90% of children with CAH are caused by this enzyme deficiency. The basic treatment is mainly lifelong use of corticosteroids. Congenital adrenocortical hyperplasia is a group of diseases caused by enzyme deficiencies in the adrenocortical hormone synthesis pathway, which is an autosomal recessive disorder with a prevalence of 1/20,000 in newborns. More than 90% of children with CAH are caused by this enzyme deficiency. Steroid 21 hydroxylase is encoded by,GYP21A2, also known as,GYP21 or P450c21, a cytochrome P450 enzyme located in the endoplasmic reticulum of the adrenal cortex. It catalyzes the conversion of 17-hydroxyprogesterone to 11-deoxycortisol (a precursor of cortisol) and progesterone to deoxycorticosterone (a precursor of aldosterone).21 A decrease or absence of hydroxylase activity would prevent the synthesis of cortisol. The adrenal cortex is stimulated by adrenergic stimulation and produces excess cortisol precursors. Some precursors can be converted to androgens, often leading to accelerated postnatal growth, and severely affected female newborns may have signs of external genital masculinization. Complicated aldosterone deficiency can cause salt loss symptoms characterized by developmental arrest, decreased blood volume, and shock. 21 hydroxylase deficiency is one of three types of CAH that can cause female masculinization, while other types of enzyme deficiency can cause male pseudohermaphroditism. The differentiation of the different types depends on hormone level measurement and genotype analysis. The clinical manifestation and typing of 21-hydroxylase deficiency can be divided into three types: salt wasting, simple masculinization and atypical type according to the degree of 21-hydroxylase deficiency. 1, salt wasting phenotype (salt wasting phenotype) is the most serious and most classic, this type is due to the complete lack of 21 hydroxylase, its cortisol and aldosterone biosynthesis are impaired in children with masculine manifestations, soon after birth can have refusal to eat, vomiting, diarrhea, body mass does not increase or decline, dehydration, hyponatremia, hyperkalemia, metabolic acidosis, etc., if the treatment is not timely. If treatment is not timely, death may occur due to circulatory failure. 2. Simple virilizing is caused by incomplete deficiency of 21 hydroxylase, but the aldosterone synthesis is normal. Females exhibit pseudohermaphroditism and show varying degrees of masculine signs at birth. In males, pseudo-precocious puberty may be asymptomatic at birth, with signs of precocious puberty appearing after the first 6 months of life. Both boys and girls show rapid physical growth, bone age beyond age, short stature in adulthood, skin and mucous membrane pigmentation, and no salt loss symptoms. 3.Mild or non-classic type, also called late-onset type, is a variant of 21 hydroxylase deficiency, often asymptomatic or showing the corresponding symptoms caused by androgen overload after birth. The clinical manifestations vary and the age of onset varies. Masculinization does not appear until childhood or adolescence. In boys, early appearance of pubic hair, precocious puberty, accelerated growth, and early bone age; in girls, delayed menarche, primary amenorrhea, hirsutism, and infertility may occur. The diagnosis of CAH in newborns and children should first consider 21 hydroxylase deficiency if the external genitalia are deformed at birth, the clitoris is enlarged, the penis is enlarged, the height in early childhood is significantly higher than that of children of the same age, but lower than normal in adulthood, the secondary sexual characteristics of females at puberty are not developed, amenorrhea, coarse voice, laryngeal nodes, heavy body hair, male distribution of pubic hair, relatively developed muscles, and pigmentation of skin and external genitalia. If the baby is found to have an early bone age, a karyotype of 46XX, elevated urinary 17 ketone alcohol and normal urinary 17 hydroxyl alcohol, and no hypertension, female masculinization and male precocious puberty caused by 11 hydroxylase deficiency can be ruled out. If a baby has salt loss, no increase in body mass or difficulty in identifying the sex of the vulva, the disease should be suspected and the necessary tests should be performed to make a diagnosis as early as possible and provide reasonable treatment to avoid salt loss crisis. In the neonatal period, attention should also be paid to differentiate the disease from pyloric stenosis and esophageal atresia. Children in childhood should be differentiated from precocious puberty, hermaphroditism, polycystic ovary syndrome (P-COS), adrenocortical tumors, gonadal tumors, etc. based on clinical manifestations and laboratory tests. Clinical evaluation of term and preterm infants Any newborn with external genital anomalies at birth, suspected CAH, or abnormal 17 hydroxyprogesterone found in newborn screening should be evaluated clinically. The evaluation includes a detailed history, physical examination, ultrasound examination of the gonads and adrenal glands, karyotype analysis, and testing of serum or plasma 17 hydroxyprogesterone levels. Serial 17-hydroxyprogesterone testing is required in preterm infants to avoid false-positive results in children with CAH. For confirming CAH in preterm infants, urinary progesterone testing is more specific than serum 17 hydroxyprogesterone, but this test is not yet widely used in clinical practice. The purpose of neonatal screening for CAH is to prevent neonatal adrenal crisis, shock and its sequelae, and to reduce mortality; to prevent female masculinization and to reduce the consequences of excessive androgen action (including the eventual cause of CAH newborn screening is mainly performed for classic 21 hydroxylase. In recent years, newborn screening for CAH has been gradually expanded abroad, and adrenal crises in children with CAH have become less common. Serum 17 hydroxyprogesterone levels are significantly elevated in patients with classic 21 hydroxylase deficiency. Serum 17 hydroxyprogesterone levels often exceed 10,000 ng/L (300 nmol/L) in randomly tested children tested by radioimmunoassay and are below 100 ng/L (3 nmol/L) in normal newborns. This method has been used to determine 17 hydroxyprogesterone levels in filter paper blood spots for newborn screening. Newborn screening is best performed 2-4 d after birth. The reference value of 17 hydroxyprogesterone in screening is based on gestational age or body mass, but it is more reasonable to divide it by gestational age. Screening can reduce the delay in diagnosis, especially for male children without obvious signs at birth, and early diagnosis can significantly reduce the incidence of adrenal crisis and morbidity and mortality. 3. Diagnosis of salt-losing CAH The electrolyte test in children with salt-losing CAH may not be significantly abnormal in the first day or weeks after birth. Serum or plasma and/or urine electrolyte levels, plasma renin activity (PRA) or direct renin levels and CYP21 molecular biology diagnosed by serial tests can be differentiated from pure masculinization. The hormonal gold standard for differentiating 21 hydroxylase deficiency from other steroid synthase deficiencies is the alpha1-24 adrenocorticotropic hormone (ACTH) stimulation test. The test is performed by intravenous push of 0.125 or 0.25 mg α1-24 ACTH, and the baseline value and serum mass concentration of 17 hydroxyprogesterone at 60 min are measured. There were no age differences in the 17-hydroxyprogesterone concentration criteria used as a reference for the diagnosis of 21-hydroxylase deficiency. The highest 17-hydroxyprogesterone mass concentrations were found in children with loss of salt after ACTH stimulation, up to 100,000 ng/L (300 nmol/L), 10,000-30,000 ng/L (300-1000 nmol/L) in children with simple masculinization, and 1,500-10,000 ng/L (50-300 nmol/L) in atypical children. Since serum or salivary 17-hydroxyprogesterone base values can be normal in patients with atypical 21-hydroxylase deficiency by random testing, the test is performed before 8Am. Third, prenatal diagnosis and treatment of families with patients with preexisting evidence of CAH should undergo genetic counseling and prenatal diagnosis to clarify the fetal condition at an early stage. The main prenatal diagnostic methods currently used are DNA analysis of placental villi or amniotic fluid cells, sex diagnosis, amniotic fluid progesterone, 17-hydroxyprogesterone and androstenedione determination. Research on prenatal diagnosis using fetal cells in maternal blood in early pregnancy to determine fetal sex and disease status is ongoing. Prenatal diagnosis can clarify whether the fetus is sick or not. In the case of a female child with the disease, appropriate doses of oral dexamethasone (DEX) in the early stages of pregnancy can be effective in preventing the development of genital malformations. The selection criteria for prenatal treatment are: 1. sibling or first-degree relative with DNA analysis confirming the presence of a mutation that causes classic CAH; 2. father with CAH; 3. access to rapid and high-quality genetic analysis; 4. start of treatment less than 9 weeks before the last menstrual period; 5. unwillingness to resort to therapeutic abortion; 6. good compliance of the mother. The dose of DEX is 20 μg/(kg.d) in 3 oral doses and the treatment should be started no later than 9 weeks of gestation. Blood pressure, body mass, glucose, glycosylated hemoglobin, plasma cortisone, dehydroepiandrosterone sulfate, and androstenedione levels should be measured every 2 months at the beginning of treatment, and plasma or urinary estriol levels should be measured after 15-20 weeks of gestation. 80% of patients receive effective treatment. Although numerous studies have not found toxic side effects of DEX for prenatal treatment of 21-hydroxylase deficiency, the long-term effects of prenatal oral DEX treatment remain unclear to date. Drug therapy 1. glucocorticoids (GC) GC can inhibit the secretion of excessive adrenocorticotropic hormone releasing hormone (CRH) and adrenal hormone by hypothalamus and pituitary gland, and inhibit the production of excessive sex hormones by adrenal gland. The classical standard drug regimen for 21-hydroxylase deficiency includes lifelong use of GC. hydrocortisone (HC) is the drug of choice. High doses of GC should be given at the start of treatment to suppress markedly elevated adrenal hormone levels, usually with HC 50 mg/(m2.d) [25 mg/(m2.d) in infancy]. The dose during the maintenance phase of treatment is 10-20 mg/(m2.d), all divided into 3 doses. Doses of up to 100 mg/(m2.d) of HC are used in the presence of adrenal crisis or other life-threatening conditions. Long-acting glucocorticoids may be used in patients who have stopped or almost stopped their growth. DEX 0.250-0.375 mg/(m2.d) once/d. Clinical studies have found that HC has less effect on growth than prednisolone and that children who are diagnosed and treated correctly with HC eventually approach normal height. Cushing-like features. The dose of GC should be maintained at the lowest dose that adequately suppresses androgens, controls symptoms of masculinization, and maintains normal growth. The dose should be adjusted in time for pediatric treatment based on hormone levels, and usually 17-hydroxyprogesterone should be controlled at partially suppressed levels of 100-1000 ng/L (3-30 nmol/L). . Excessive GC may lead to the development of medical Cushing’s syndrome, although 17-hydroxyprogesterone can be kept at normal levels. Levels of androstenedione and testosterone should be maintained at levels appropriate for age and gender. Other indicators of efficacy include assessment of bone age and monitoring of growth curves. Asymptomatic infants or children with atypical 21-hydroxylase deficiency often do not require treatment. Infants with atypical CAH found during neonatal screening should be closely tested for signs of androgen overload and treated promptly. 2. Mineralocorticoids (MC) MC can synergize with GC to further reduce ACTH secretion in children with CAH. In addition to GC treatment, MC treatment should be given to infants with salt loss, usually fludrocortisone 0.1-0.2 mg/d. At the same time, sodium should be supplemented to correct water and electrolyte disorders, with 1-2 g of sodium chloride or 17-34 mmol of sodium per day. 3. Growth hormone (GH) and gonadotropin-releasing hormone analog (GnRHa) GC replacement therapy. GnRHa) GC replacement therapy has been used as the basic treatment for CAH, but its growth-inhibiting effect together with the long-term hyperandrogenism limits the height growth of children with CAH. Although children are often taller than normal at the beginning of the disease, most children end up short due to precocious puberty and accelerated epiphyseal healing. Recent studies have shown that GH is effective in increasing the growth rate of children receiving long-term GC therapy, and that the combination of GC and GnRHa improves the final height of children with central precocious puberty. Lin-Su et al. combined GH [0.3 mg/(kg.week) in 7 injections] with luteinizing hormone-releasing hormone analogue (LHRHa, 300 μg/kg intramuscularly every 4 weeks) in children with CAH puberty and found that this regimen significantly improved the final height of the children. counteract the growth rate decrease induced by LHRHa and GC treatment. In this study, central puberty was defined as peak LH/FSH greater than 1 after a 2-h intramuscular LHRH stimulation test, and cessation of GH treatment was defined as a growth rate of less than 1.5 cm/year for more than 6 months and a bone age greater than 15 years (female) or greater than 17 years (male). The time of cessation of LHRHa treatment is defined as the actual age of the child at which the predicted height reaches or exceeds the target height or the growth rate is less than 3 cm/year for more than 6 months and the bone age is greater than 13 years (female) or greater than 14 years (male). Human insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP3), glycated hemoglobin level and thyroid function should be monitored during treatment. Early treatment and surgical correction of deformities are important for the physical and psychological health of the child. The best time for surgery is currently considered to be 2-6 months, when the child’s tissues are highly plastic and the psychological damage to the child is minimal. the preoperative or preanesthetic management plan for classic CAH patients is shown in Table 1.