| 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 masculinizing effects on the urogenital system and genital tubercle, causing the vagina and urethra to fuse and the clitoris to become hypertrophied, low-set, and open. The labia are often hypertrophied 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 20-22 carbon chainase 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 leads to impaired synthesis of progesterone, aldosterone, and cortisol, while dehydroepiandrosterone is overproduced. This unusual syndrome is characterized by hypotension, hypoglycemia, and male pseudohermaphroditism. Females exhibit uncommon hirsutism with variable melanin deposition.
Insufficiency or deficiency of 21-hydroxylase prevents the conversion of 17-hydroxyprogesterone to cortisol. The more common insufficiency manifests in two forms: (1) varied sodium loss with low or absent aldosterone; (2) more frequently, the non-salt-losing type, featuring hirsutism, masculinization, hypotension, and pigmentation.
17α-hydroxylase deficiency, most commonly seen in female patients, may present in adulthood with low cortisol levels and compensatory elevated ACTH. Primary amenorrhea, sexual infantilism, and rare male pseudohermaphroditism occur. Excessive mineralocorticoid secretion causes hypertension, primarily due to elevated 11-deoxycorticosterone.11β-hydroxylase deficiency blocks the formation of cortisol and corticosterone, leading to excessive ACTH release, profound melanin deposition, and hypertension due to excessive 11-deoxycorticosterone secretion, without significant sexual abnormalities.
18-hydroxysteroid dehydrogenase deficiency is a rare condition caused by a specific blockade in the final step of aldosterone biosynthesis, resulting in excessive urinary sodium loss, dehydration, and hypotension.
Post-puberty, hirsutism and amenorrhea—signs of masculinization—are rarely observed. Occasionally, masculinization may appear in middle age. This acquired adrenal grade I enzyme abnormality is termed benign adrenal cortical masculinization.
Newborn female genitalia may resemble severe hypospadias and cryptorchidism, while male infants are usually normal at birth, though excessive androgen exposure in utero may already cause significant abnormalities.
Untreated patients develop hirsutism, muscular build, amenorrhea, and breast development. Male patients exhibit abnormally large genitalia. Excessive androgens suppress gonadotropin secretion, leading to testicular atrophy. In extremely rare cases, hyperplastic adrenal cortical remnants in the testes cause enlargement and hardening. Most patients experience aspermia post-puberty due to adrenal cortical hyperplasia. Between ages 3–8, rapid height increase makes these children significantly taller than peers. Around ages 9–10, excessive androgens cause early epiphyseal fusion, halting growth and resulting in short stature in adulthood. Both genders display aggressive behavior and heightened 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 of urinary progesterone levels (this is more sensitive than 17-KS levels, as progesterone is a precursor to androgens), and increased 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 reveal significantly enlarged adrenal glands. Urethroscopy can visualize the vagina opening on the posterior urethral wall and also enter the vagina to observe the uterus.
bubble_chart Treatment Measures
Early diagnosis is absolutely essential. The appropriate treatment involves administering glucocorticoids, specifically oral dexamethasone at 0.5–1.5 mg taken at 11 p.m. daily to correct deficiencies and suppress ACTH secretion. For patients with severe salt-losing syndrome, fludrocortisone helps maintain blood pressure and body weight, with a dosage of 0.05–0.3 mg depending on the severity of the condition and 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 clitoral erection is frequent, clitoral resection may be considered. Cautious administration of estrogen or early postnatal hormonal regulation can help maintain a female appearance and improve psychological well-being in patients with pseudohermaphroditism.
If diagnosed early, even before surgical correction of severe organ malformations, suppression of ACTH secretion can begin. Then, the appearance can be normal, and development can 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 conceive and give birth.
Many congenital malformations affecting the development of the external genitalia resemble adrenogenital syndrome, including:
- severe hypospadias and cryptorchidism;
- non-adrenal female pseudohermaphroditism (due to excessive androgen or progestin medication during pregnancy);
- male pseudohermaphroditism;
- true hermaphroditism.
