Congenital adrenal hyperplasia

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

Feature	21-Hydroxylase Deficiency	11β-Hydroxylase Deficiency	17α-Hydroxylase Deficiency
Prevalence	Most Common (>90%)	~5%	Rare
Mineralocorticoids	↓ Aldosterone	↑ 11-deoxycorticosterone (weak activity)	↑ Corticosterone (weak activity)
Blood Pressure	Hypotension (Salt-wasting)	Hypertension	Hypertension
Potassium (K+)	Hyperkalemia (↑)	Hypokalemia (↓)	Hypokalemia (↓)
Sex Steroids	↑ Androgens	↑ Androgens	↓↓ Androgens & Estrogens
Genitalia (XX)	Virilization (Ambiguous)	Virilization (Ambiguous)	Female (Sexual Infantilism)
Genitalia (XY)	Normal	Normal	Ambiguous or Female
Key Lab	↑ 17-hydroxyprogesterone	↑ 11-deoxycorticosterone	↑ Corticosterone, ↓ DHEA
Buzzword Triad	Hypotension + Virilization + ↑ K+	Hypertension + Virilization + ↓ K+	Hypertension + Sexual Infantilism + ↓ K+

Tip

For both 21- AND11- hydroxylase deficiencies: ↑ 17-OH substrates (i.e., 17-OH-progesterone and 17-OH-pregnenolone)

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