Epidemiology

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Etiology

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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

ENZYME DEFICIENCY	MINERALOCORTICOIDS	$[K^{+}]$	BP	CORTISOL	SEX HORMONES	LABS	PRESENTATION
17$\alpha$-hydroxylase${}^a$	$\downarrow$ aldosterone $\uparrow$ 11-deoxycorticosterone${}^b$	$\downarrow$	$\uparrow$	$\downarrow$	$\downarrow$	$\downarrow$ androstenedione	XY: atypical genitalia, undescended testes XX: lacks 2${}^{\circ }$ sexual development
21-hydroxylase${}^a$	$\downarrow$	$\uparrow$	$\downarrow$	$\downarrow$	$\uparrow$	$\uparrow$ renin activity $\uparrow$ 17-hydroxyprogesterone	Most common Presents in infancy (salt wasting) or childhood (precocious puberty) XX: virilization
11$\beta$-hydroxylase${}^a$	$\downarrow$ aldosterone $\uparrow$ 11-deoxycorticosterone${}^b$	$\downarrow$	$\uparrow$	$\downarrow$	$\uparrow$	$\downarrow$ 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 $\uparrow$ MSH production, which is coproduced and secreted with ACTH) and bilateral adrenal gland enlargement (due to $\uparrow$ ACTH stimulation). ${}^b$Results in $\uparrow$ 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.

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Clinical features

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Diagnostics

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Treatment

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• 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