Congenital adrenal hyperplasia

Epidemiology

Etiology

Pathophysiology

There are three subtypes of CAH:
- 21β-hydroxylase (∼ 95% of CAH)
- 11β-hydroxylase (∼ 5% of CAH)
- 17α-hydroxylase (rare)
Foa all 3 subtypes, cortisol production is defected.
Low levels of cortisol → lack of negative feedback to the pituitary → increased ACTH → adrenal hyperplasia and increased synthesis of adrenal precursor steroids

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ENZYME DEFICIENCY	MINERALOCORTICOIDS	$[K^{+}]$	BP	CORTISOL	SEX HORMONES	LABS	PRESENTATION
17 $α$ -hydroxylase $^{a}$	$↓$ aldosterone $↑$ 11-deoxycorticosterone $^{b}$	$↓$	$↑$	$↓$	$↓$	$↓$ androstenedione	XY: atypical genitalia, undescended testes XX: lacks 2 $^{\circ}$ sexual development
21-hydroxylase $^{a}$	$↓$	$↑$	$↓$	$↓$	$↑$	$↑$ renin activity $↑$ 17-hydroxyprogesterone	Most common Presents in infancy (salt wasting) or childhood (precocious puberty) XX: virilization
11 $β$ -hydroxylase $^{a}$	$↓$ aldosterone $↑$ 11-deoxycorticosterone $^{b}$	$↓$	$↑$	$↓$	$↑$	$↓$ renin activity	Presents in infancy (severe hypertension) or childhood (precocious puberty) XX: virilization

$^{a}$ All congenital adrenal enzyme deficiencies are autosomal recessive disorders and most are characterized by skin hyperpigmentation (due to $↑$ MSH production, which is coproduced and secreted with ACTH) and bilateral adrenal gland enlargement (due to $↑$ ACTH stimulation).
$^{b}$ Results in $↑$ BP.

Tip

DOC (11-Deoxycorticosterone) has aldosterone-like activity, and in high levels, it causes hypertension and kaluresis and inhibits the production of renin and consequently aldosterone.

Mnemonic

“1 DOC:” If the deficient enzyme starts with 1 (11β-, 17‑), there is increased DOC.
“AND 1:” If the deficient enzyme ends with 1 (21-, 11β‑), androgens are increased.

Clinical features

Diagnostics

Treatment

Glucocorticoid replacement therapy is indicated in all forms of CAH.
Specific treatment
- 21β-hydroxylase deficiency
  - Lifelong fludrocortisone therapy (aldosterone substitution)
  - Sodium chloride (salt) supplements, especially during infancy and childhood
- 11β-hydroxylase deficiency
  - Spironolactone to block mineralocorticoid receptors
  - Reduced dietary sodium intake
- 17α-hydroxylase deficiency
  - Spironolactone to block mineralocorticoid receptors
  - Estrogen replacement therapy for female genotype; may be started in early puberty
  - Reduced dietary sodium intake