Question

Congenital adrenal hyperplasia (CAH) occurs because of a deficiency in CYP21A2, a 21-hydroxylase of endoplasmic reticulum. The disease results in decreased cortisol, increased ACTH, increased androgenic hormones, and problems related to salt balance. Explain why these should be so.

Short answer

Question: Explain the main effects of Congenital Adrenal Hyperplasia (CAH) due to a deficiency in the enzyme 21-hydroxylase. Answer: The main effects of CAH due to a deficiency in 21-hydroxylase include decreased cortisol levels, leading to fatigue and poor stress response; increased ACTH levels due to the body trying to compensate for low cortisol levels; increased androgenic hormones, causing virilization and early puberty; and problems related to salt balance, potentially resulting in dehydration, low blood pressure, and electrolyte imbalances.

Step-by-step solution

Understanding Congenital Adrenal Hyperplasia (CAH)

CAH is an autosomal recessive disorder that occurs due to a deficiency in the CYP21A2 gene encoding for the enzyme 21-hydroxylase. This enzyme plays an important role in the biosynthesis of steroid hormones, particularly cortisol and aldosterone, in the adrenal cortex. Therefore, when 21-hydroxylase is deficient, the adrenal cortex cannot properly synthesize these hormones, leading to the clinical manifestations of the disease.

Decreased cortisol levels

Cortisol is a steroid hormone produced by the adrenal cortex that helps regulate the body's stress response and maintains glucose levels. In the absence of sufficient 21-hydroxylase, cortisol production is impaired, resulting in decreased levels of cortisol. This can lead to symptoms such as fatigue, low blood sugar, and poor stress response.

Increased ACTH levels

Adrenocorticotropic hormone (ACTH) is a hormone produced by the pituitary gland to stimulate the synthesis of cortisol in the adrenal cortex. When cortisol levels are low due to deficient 21-hydroxylase, the body tries to compensate by increasing ACTH secretion. This is a result of the negative feedback loop between cortisol levels and ACTH production. The pituitary gland senses the low cortisol levels and responds by secreting more ACTH to stimulate cortisol production.

Increased androgenic hormones

Since 21-hydroxylase is involved in the synthesis of cortisol and aldosterone, its deficiency causes a buildup of precursors that are shunted into the production of androgenic hormones, such as testosterone and androstenedione. This excess production of androgenic hormones can lead to virilization (masculinization) in females, early puberty in both males and females, and other clinical manifestations of excess androgens.

Problems related to salt balance

Aldosterone is a mineralocorticoid hormone produced by the adrenal cortex that plays an important role in regulating salt (sodium) and potassium balance in the body. It does this by increasing the reabsorption of sodium and the secretion of potassium in the kidneys. Since the synthesis of aldosterone is impaired due to the deficiency of 21-hydroxylase, affected individuals can experience problems related to salt balance. This may manifest as salt-wasting, which can cause dehydration, low blood pressure, and potentially life-threatening electrolyte imbalances if not properly managed. In summary, the deficiency of the enzyme 21-hydroxylase in CAH leads to decreased cortisol and aldosterone production, increased ACTH and androgenic hormones, and problems related to salt balance in the body.