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Clinical Subject Page

Congenital Adrenal Hyperplasia (CAH)

Cushing Syndrome is a clinical disorder caused by prolonged exposure to excessive glucocorticoids, either from exogenous corticosteroid therapy or endogenous overproduction of cortisol

Also called

21-Hydroxylase Deficiency

ICD-10

E25.0

Specialty

Endocrine

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

–Congenital Adrenal Hyperplasia (CAH) results from impaired adrenal steroid production.

  • Approximately 90–95% of CAH cases are caused by 21-hydroxylase deficiency.

–Depending on the severity of enzyme deficiency, patients may develop:

      • Cortisol deficiency
      • Aldosterone deficiency
      • Androgen excess
      • Salt-wasting adrenal crisis
      • Virilization
      • Precocious puberty

Etiology & Risk Factors

-Etiology:

–Congenital Adrenal Hyperplasia (CAH) is caused by inherited defects in enzymes involved in adrenal steroidogenesis.

 

-The most common defect is:

21-Hydroxylase Deficiency

Caused by pathogenic variants in the CYP21A2 gene.

 

-This leads to:

↓ cortisol synthesis → ↑ ACTH → adrenal hyperplasia → accumulation of steroid precursors → ↑ androgen production

 

-Other, less common forms include deficiencies of:

  • 11β-hydroxylase
  • 17α-hydroxylase/17,20-lyase
  • 3β-hydroxysteroid dehydrogenase

 

-Risk Factors:

  • Family history of Congenital Adrenal Hyperplasia (CAH)
  • Previous child with Congenital Adrenal Hyperplasia (CAH)
  • Parents who are carriers
  • Consanguinity

Pathophysiology

-21-Hydroxylase Deficiency

21-hydroxylase deficiency → ↓ cortisol ± ↓ aldosterone → ↓ negative feedback → ↑ ACTH → adrenal hyperplasia → accumulation of steroid precursors → ↑ adrenal androgen production → virilization/precocious puberty

↓ aldosterone → ↓ renal sodium reabsorption → sodium loss + water loss → dehydration + hypotension → hyperkalemia → salt-wasting adrenal crisis

Clinical Presentation

-Symptoms:

–Classic Congenital Adrenal Hyperplasia (CAH)

  • Poor feeding
  • Vomiting
  • Dehydration
  • Weakness
  • Salt craving

 

-Androgen Excess

  • Early pubic hair
  • Precocious puberty
  • Hirsutism in females
  • Infertility

 

–Nonclassic Congenital Adrenal Hyperplasia (CAH)

    • Hirsutism
    • Infertility
    • Premature pubarche

-Signs:

  • Central obesity
  • Rounded “moon face”
  • Facial plethora
  • Dorsocervical fat accumulation (buffalo hump)
  • Easy bruising
  • Acne
  • Hirsutism

History Taking

-Ask about:

  • Family history of Congenital Adrenal Hyperplasia (CAH)
  • Previous affected siblings
  • Consanguinity
  • Prenatal genetic testing
  • Abnormal newborn screening
  • Feeding difficulties
  • Vomiting
  • Weight loss
  • Dehydration
  • Salt craving
  • Episodes of adrenal crisis
  • Early pubic hair
  • Rapid growth
  • Acne
  • Hirsutism

Physical Examination

-General Examination

    • Height
    • Weight
    • Growth velocity
    • Blood pressure
    • Hydration status

       

      -Look for:

      • Dehydration
      • Hypotension
      • Poor growth or abnormal growth pattern
      • Signs of androgen excess

-System-Specific Examination:

–Genital Examination

-In affected females:

  • Clitoromegaly
  • Labial fusion
  • Virilization

 

-In males:

  • Penile enlargement
  • Testicular size
  • Signs of precocious puberty

 

–Skin

  • Acne
  • Hirsutism
  • Excess terminal hair
  • Virilization

Investigations

-Biochemistry / Specific Tests

Important tests include:

  • 17-hydroxyprogesterone (17-OHP)
  • Serum cortisol
  • ACTH
  • Serum electrolytes
  • Plasma renin activity or renin concentration
  • Aldosterone
  • Androgen levels
  • Androstenedione
  • Testosterone

 

-Typical Salt-Wasting CAH Findings

  • ↓ cortisol
  • ↑ ACTH
  • ↑ 17-OHP
  • ↑ adrenal androgens
  • ↓ aldosterone
  • ↑ renin
  • Hyponatremia
  • Hyperkalemia
  • Possible hypoglycemia

 

-Special / Confirmatory Tests

17-Hydroxyprogesterone

Markedly elevated 17-OHP strongly suggests 21-hydroxylase deficiency

 

-Genetic Testing

CYP21A2 genetic testing can help confirm the diagnosis and is useful for:

  • Genetic counseling
  • Family studies

Diagnosis

-Diagnosis of Congenital Adrenal Hyperplasia (CAH) is based on :

↑ 17-hydroxyprogesterone + evidence of cortisol deficiency/androgen excess ± aldosterone deficiency → diagnosis of CAH

-Further assessment determines whether the patient has:

  • Classic salt-wasting Congenital Adrenal Hyperplasia (CAH)
  • Classic simple-virilizing Congenital Adrenal Hyperplasia (CAH)
  • Nonclassic Congenital Adrenal Hyperplasia (CAH)
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Management

1. First-Line / Emergency Management

-Adrenal Crisis

Immediate treatment includes:

  • IV hydrocortisone
  • Rapid IV isotonic fluid replacement
  • Correction of hypoglycemia
  • Correction of significant electrolyte abnormalities
  • Treatment of the precipitating illness

Treatment should not be delayed while awaiting laboratory confirmation.

2. Definitive Treatment

Long-term treatment aims to:

  • Replace deficient cortisol
  • Replace mineralocorticoid when necessary
  • Suppress excessive ACTH
  • Reduce excessive androgen production
  • Prevent adrenal crisis
  • Support normal growth and puberty

3. Medical Treatment

Glucocorticoid Replacement

-Common options include:

  • Hydrocortisone
  • Prednisolone
  • Dexamethasone in selected older patients

Hydrocortisone is commonly preferred in children because of its shorter duration of action and greater flexibility for physiological replacement.

-Mineralocorticoid Replacement

Fludrocortisone is used in patients with mineralocorticoid deficiency, particularly classic salt-wasting CAH.

Complications

  • Adrenal crisis
  • Severe dehydration
  • Hypotension
  • Hyperkalemia
  • Hyponatremia
  • Hypoglycemia
  • Virilization
  • Precocious puberty
  • Advanced bone age
  • Reduced final adult height
  • Menstrual irregularities

Prognosis

-With early diagnosis and appropriate lifelong treatment, most Congenital Adrenal Hyperplasia (CAH) patients can lead healthy lives.

-Prognosis depends on:

  • Severity of enzyme deficiency
  • Early recognition
  • Prevention of adrenal crisis
  • Adequacy of hormone replacement
  • Growth and pubertal control

Key Points / Clinical Pearls

  • Congenital Adrenal Hyperplasia (CAH) is an inherited disorder of adrenal steroid synthesis.
  • Most cases are caused by 21-hydroxylase deficiency.
  • CAH is usually inherited in an autosomal recessive pattern.
  • 21-hydroxylase deficiency causes ↓ cortisol ± ↓ aldosterone + ↑ adrenal androgens.
  • Reduced cortisol causes ↑ ACTH → adrenal hyperplasia.
  • Excess androgen production causes virilization and precocious puberty.
  • Severe disease can cause salt wasting, dehydration, hyperkalemia, and adrenal crisis.
  • 17-hydroxyprogesterone is the key biochemical marker for 21-hydroxylase deficiency.
  • Newborn screening can identify affected infants before a potentially fatal adrenal crisis develops.
  • Classic CAH includes salt-wasting and simple-virilizing forms.