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Congenital adrenal hyperplasia

Properties2
tagst1
aliasesCongenital adrenal hyperplasias, CAH, Adrenal hyperplasia

2 min read

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

Feature21-Hydroxylase Deficiency11β-Hydroxylase Deficiency17α-Hydroxylase Deficiency
PrevalenceMost Common (>90%)~5%Rare
Mineralocorticoids↓ Aldosterone↑ 11-deoxycorticosterone (weak activity)↑ Corticosterone (weak activity)
Blood PressureHypotension (Salt-wasting)HypertensionHypertension
Potassium (K+)Hyperkalemia (↑)Hypokalemia (↓)Hypokalemia (↓)
Sex Steroids↑ Androgens↑ Androgens↓↓ Androgens & Estrogens
Genitalia (XX)Virilization (Ambiguous)Virilization (Ambiguous)Female (Sexual Infantilism)
Genitalia (XY)NormalNormalAmbiguous or Female
Key Lab↑ 17-hydroxyprogesterone↑ 11-deoxycorticosterone↑ Corticosterone, ↓ DHEA
Buzzword TriadHypotension + 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) c

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

  • 21-OH deficiency:
    • Classic salt-wasting (severe): Presents at 1-2 weeks of life with failure to thrive, vomiting, dehydration, and hypotension/shock. Females present with atypical/ambiguous genitalia (virilization/clitoromegaly) at birth. Males have normal genitalia but may have scrotal hyperpigmentation.
    • Classic simple virilizing (moderate): No salt-wasting. Females have ambiguous genitalia at birth. Males present in early childhood with premature pubarche, accelerated growth velocity, but short adult stature due to premature epiphyseal plate closure.
    • Non-classic/Late-onset (mild): Normal electrolytes. Presents in childhood/adolescence. Females present with signs of androgen excess (e.g., severe acne, hirsutism, irregular menses, infertility). Males present with premature pubarche, acne, and advanced bone age. c

Diagnostics

Differential diagnostics

  • Polycystic Ovary Syndrome (PCOS):
    • Diff vs. Non-classic CAH: PCOS presents with bilateral polycystic ovaries on US and normal or only mildly elevated 17-OHP. CAH has significantly elevated 17-OHP and diagnostic CYP21A2 mutations.

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

Graph View

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