| disease | Bilateral Congenital Adrenal Hyperplasia |
Congenital defects in certain adrenal enzymes lead to abnormal steroid production. In females, this causes pseudohermaphroditism, while in males, it results in enlarged genitalia. The enzyme deficiency is accompanied by excessive androgen production in the fetal uterus. In females, the Müllerian duct structures (i.e., ovaries, uterus, and vagina) develop normally, but the excess androgens exert their masculinizing effects on the urogenital system and genital tubercle, causing the vagina and urethra to connect and the clitoris to become hypertrophied, low, and open. The labia are often enlarged as well, and severe cases may present with hypospadias and cryptorchidism. The adrenal cortex, due to the predominant secretion of anabolic androgenic steroids, leads to varying degrees of cortisol deficiency.
bubble_chart Clinical Manifestations
Increased secretion of ACTH leads to bilateral adrenal cortical hyperplasia. The hyperplastic cortex continuously synthesizes large amounts of androgens and hypertensive mineralocorticoids.
Deficiency of the 20–22 carbon chain enzyme results in rare congenital lipoid adrenal hyperplasia, often accompanied by complete impairment of steroid hormone production. Without adequate replacement therapy, infants will die early.
Deficiency of 3β-hydroxysteroid dehydrogenase isomerase impairs the synthesis of progesterone, aldosterone, and cortisol, while dehydroepiandrosterone is overproduced. This unusual syndrome is characterized by hypotension, hypoglycemia, and male pseudohermaphroditism. In females, it manifests as uncommon hirsutism with variable melanin deposition.
Deficiency or absence of 21-hydroxylase prevents the conversion of 17-hydroxyprogesterone to cortisol. The deficiency commonly presents in two forms: (1) varied sodium loss, with low or absent aldosterone; (2) more commonly, the non-salt-losing type, featuring hirsutism, masculinization, hypotension, and pigmentation.
17α-hydroxylase deficiency is most frequently seen in female patients, some of whom exhibit low cortisol levels and compensatory increases in ACTH by adulthood. Primary amenorrhea and sexual infantilism are common, with rare cases of male pseudohermaphroditism. Excessive secretion of mineralocorticoids, primarily 11-deoxycorticosterone, leads to hypertension.11β-hydroxylase deficiency blocks the formation of cortisol and corticosterone, resulting in excessive ACTH release, profound melanin deposition, and hypertension due to overproduction of 11-deoxycorticosterone, without significant sexual abnormalities.
18-hydroxysteroid dehydrogenase deficiency is a rare condition caused by a specific blockade in the final step of aldosterone biosynthesis. Patients experience excessive urinary sodium loss, leading to dehydration and hypotension.
Post-puberty, hirsutism and amenorrhea, among other masculinizing manifestations, are rarely observed. Occasionally, masculinization may occur in middle age. This acquired adrenal grade I enzyme abnormality is termed benign adrenal cortical masculinization.
Newborn female infants may exhibit external genitalia resembling severe hypospadias and cryptorchidism, while male infants are usually normal at birth. Excessive androgen exposure in utero already causes significant abnormalities.
Untreated patients develop hirsutism, muscular build, amenorrhea, and breast development. Male patients may have unusually large genitalia. Excessive androgens suppress gonadotropin secretion, leading to testicular atrophy. In extremely rare cases, hyperplastic adrenal cortical remnants within the testes cause enlargement and hardening. Most patients experience aspermia after puberty. Due to adrenal cortical hyperplasia, patients experience a sudden growth spurt at ages 3–8, making them significantly taller than their peers. Around ages 9–10, excessive androgens lead to early epiphyseal fusion, halting growth and resulting in short stature in adulthood. Both genders may exhibit aggressive behavior and increased libido, leading to social and disciplinary issues, particularly in some boys.
The urinary 17-ketosteroid levels are higher than normal for individuals of the same sex and age. Early elevation in urinary progesterone levels (which is more sensitive than 17-KS levels, as progesterone is a precursor to androgens), and elevated blood 17-hydroxyprogesterone levels are the most sensitive indicators, suitable for children with normal chromosomal tests. X-ray examination may reveal advanced bone age. Lateral urethrocystography will show the vagina, urethra, and bladder. CT scans can detect significantly enlarged adrenal glands. Urethroscopy can visualize the vagina opening on the posterior urethral wall and also allow entry into the vagina to observe the uterus.
bubble_chart Treatment Measures
Early diagnosis is absolutely essential. The appropriate treatment involves administering glucocorticoids, specifically taking 0.5–1.5 mg of dexamethasone orally at 11 p.m. daily to correct the deficiency and suppress ACTH secretion. For patients with severe salt-losing syndrome, fludrocortisone can help maintain blood pressure and body weight, with a dosage of 0.05–0.3 mg depending on the severity of the condition and the patient’s age.
After development, surgery can be performed to separate the vagina from the urethra and position the vaginal opening in the normal perineal location. If the clitoris frequently becomes erect, clitoral resection may be considered. Cautious administration of estrogen or early postnatal hormonal therapy can help maintain a female appearance and improve the psychological state of patients with pseudohermaphroditism.
If diagnosed early, even before surgical correction of severe organ malformations, suppression of ACTH secretion can begin. The appearance can then be normal, and development will be excellent. Delayed treatment inevitably leads to growth retardation, and if complicated by coronary heart disease, early death from myocardial infarction may occur. In some cases of female pseudohermaphroditism, menstruation may occur after treatment. If the malformation is not severe or has been surgically corrected, the patient may become pregnant and give birth.
Many congenital malformations affecting the development of external genitalia resemble adrenogenital syndrome, including: (1) severe hypospadias and cryptorchidism; (2) non-adrenal female pseudohermaphroditism (due to excessive androgen or progestin medication during pregnancy); (3) male pseudohermaphroditism; (4) true hermaphroditism. These children show no hormonal abnormalities, and their bone age and maturation are not advanced.
