Causes, Symptoms & Signs of Congenital Adrenal Hyperplasia

What are the Causes of Congenital Adrenal Hyperplasia (CAH)?

Congenital Adrenal Hyperplasia (CAH) is caused by the deficiency of steroid hormone synthesizing enzymes, which occur due to mutations in their corresponding genes. For example, the most common form of CAH, accounting for 90-95% of cases, occurs due to 21-hydroxylase deficiency, which results from mutations in the CYP21A2 gene.

Other types of CAH are caused by their corresponding enzyme deficiencies. These enzyme deficiencies with their corresponding gene mutations and type of CAH (Classic i.e. severe form or Non-classic i.e. mild form) are tabulated below:

Type of CAH	Deficient Enzyme	Mutated Gene
Classic	21-hydroxylase	CYP21A2
Non-classic	3-beta-hydroxysteroid dehydrogenase	HSD3B2
Classic and Non-classic	11-beta-hydroxylase	CYP11B1
Non-classic	Cytochrome P450 oxidoreductase	POR
Non-classic	17-hydroxylase	CYP17A1

Mutations in the genes lead to deficiency in the enzymes, which lowers the levels of hormones like cortisol and/or aldosterone and over-production of androgens such as testosterone.

Cortisol regulates energy levels in the body, blood sugar levels, blood pressure, as well as the body’s response to injury, stress, and illness. Aldosterone helps to maintain optimal levels of sodium and water, which in turn, regulates blood pressure. Any fluctuations in these hormones can give rise to symptoms and signs of CAH.

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What are the Symptoms & Signs of Congenital Adrenal Hyperplasia (CAH)?

The symptoms and signs of CAH depend on the type of CAH, which include the following:

• Classic CAH: This is the more severe form of CAH.
• Non-classic CAH: This is the milder form of CAH.

Symptoms also depend on the age of diagnosis and the sex of the patient. Some of the common symptoms in different categories of patients include the following:

Symptoms Exclusively in Males

• Undescended testes (cryptorchidism)
• Small testes
• Absent scrotum
• Cleft in the scrotum or bifid scrotum
• Enlarged male breast (gynecomastia)

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Symptoms Exclusively in Females

• Excessive facial / body hair
• Irregular menstrual pattern
• Acne
• Enlarged clitoris (clitoral hypertrophy)
• Small uterus
• Underdeveloped vagina
• Female pseudo-hermaphroditism – where a female genitalia looks like a male due to enlarged clitoris as this resembles the male phallus

Symptoms in Both Males and Females

• Enlarged adrenal glands (adrenal hyperplasia)
• Early onset of puberty
• Accelerated bone maturation
• Short stature
• Ambiguous genitalia

Symptoms in Infants

• Failure to thrive or live
• Feeding difficulties

What is Adrenal Crisis?

The consequences depend on the type of Congenital Adrenal Hyperplasia (CAH) and its severity. A major consequence of classic CAH is the occurrence of adrenal crisis, which is caused by extremely low levels of blood cortisol. Adrenal crisis is life-threatening and is a medical emergency that requires prompt treatment. The symptoms include -

• Low blood sugar
• Diarrhea
• Vomiting
• Dehydration
• Shock

Aldosterone production may be impaired, resulting in low sodium and high potassium levels in the blood.  Adrenal crisis doesn’t occur in non-classic form of CAH.

Another consequence is the occurrence of fertility problems, both in males and in females. This can occur in case of classic as well as non-classic forms of CAH.