Congenital adrenal hyperplasia

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Congenital adrenal hyperplasia
File:Steroidogenesis.svg
Synonyms	CAH
Pronounce	N/A
Specialty	N/A
Symptoms	Ambiguous genitalia, early puberty, infertility, hirsutism, acne
Complications	Adrenal crisis, hypertension, infertility
Onset	Birth
Duration	Lifelong
Types	N/A
Causes	Genetic mutation in steroidogenesis
Risks	Family history
Diagnosis	Newborn screening, blood test for 17-hydroxyprogesterone
Differential diagnosis	Androgen insensitivity syndrome, 5-alpha-reductase deficiency
Prevention	Genetic counseling
Treatment	Glucocorticoid replacement, mineralocorticoid replacement
Medication	Hydrocortisone, fludrocortisone
Prognosis	Variable, depends on treatment adherence
Frequency	1 in 10,000 to 1 in 15,000 live births
Deaths	Rare with treatment

Congenital Adrenal Hyperplasia

File:Steroidogenesis.svg

Diagram of steroidogenesis, showing the pathways involved in the synthesis of steroid hormones.

Congenital adrenal hyperplasia (CAH) is a group of inherited genetic disorders that affect the adrenal glands, which are responsible for producing vital hormones such as cortisol, aldosterone, and androgens. CAH is characterized by a deficiency in one of the enzymes needed for the synthesis of these hormones, leading to an overproduction of androgenic steroids and a variety of clinical manifestations.

Pathophysiology

The most common form of CAH is due to a deficiency in the enzyme 21-hydroxylase, which is crucial in the steroidogenesis pathway. This enzyme deficiency leads to impaired synthesis of cortisol and aldosterone, resulting in an accumulation of precursor steroids that are shunted into the androgen synthesis pathway, causing an overproduction of androgens.

Steroidogenesis

File:Steroidogenesis.svg

Steroidogenesis pathway showing enzyme deficiencies in CAH.

Steroidogenesis is the biological process by which steroids are generated from cholesterol and transformed into other steroids. In CAH, the disruption of this pathway due to enzyme deficiencies leads to hormonal imbalances. The diagram illustrates the steroidogenesis pathway, highlighting the role of 21-hydroxylase and other enzymes involved in the synthesis of adrenal steroids.

Clinical Manifestations

The clinical presentation of CAH varies depending on the specific enzyme deficiency and the severity of the enzyme defect. Common symptoms include:

• Virilization: Excess androgen production can lead to virilization in females, resulting in ambiguous genitalia at birth.
• Salt-wasting crisis: In severe cases, the lack of aldosterone can lead to a life-threatening salt-wasting crisis, characterized by hyponatremia, hyperkalemia, and dehydration.
• Precocious puberty: In both males and females, early exposure to high levels of androgens can cause early onset of puberty.

Diagnosis

Diagnosis of CAH is typically made through newborn screening programs that measure levels of 17-hydroxyprogesterone, a precursor that accumulates in 21-hydroxylase deficiency. Confirmatory tests include genetic testing and hormone assays.

Treatment

The primary treatment for CAH involves hormone replacement therapy to correct the deficiencies in cortisol and aldosterone. Glucocorticoids are used to replace cortisol, while mineralocorticoids are used to replace aldosterone in salt-wasting forms of CAH. Additionally, surgical intervention may be necessary to correct ambiguous genitalia in affected females.

See Also

• Adrenal gland
• Endocrinology
• Genetic disorder
• Hormone replacement therapy