What is the recommended treatment for Congenital Adrenal Hyperplasia (CAH)?

Treatment of Congenital Adrenal Hyperplasia (CAH)

Patients with CAH require lifelong glucocorticoid replacement with hydrocortisone as the first-line agent at 15-25 mg daily in divided doses, combined with mineralocorticoid replacement using fludrocortisone 0.1-0.2 mg daily for salt-losing forms. 1, 2

Glucocorticoid Replacement

First-Line Therapy

• Hydrocortisone (HC) is the preferred glucocorticoid for CAH treatment in both children and adults 1, 3
• Standard adult dosing: 15-25 mg per day in 2-3 divided doses 1
• Dosing schedule: First dose upon awakening, last dose 4-6 hours before bedtime 1
• Available tablet strengths: 20 mg, 10 mg, and 2.5 mg 1

Alternative Glucocorticoid Options

• Cortisone acetate (CA) can be used as an alternative to HC, though it has delayed onset requiring hepatic activation 1
• CA dosing: 25 mg and 5 mg tablets, taken in divided doses 1
• Dexamethasone may be used in adults with doses ranging from 0.0625 to 0.875 mg/day (mean 0.4 mg/day), though this is considerably lower than traditionally recommended 4
• Prednisone is FDA-approved for CAH but is not preferred over HC in children 5

Critical Dosing Principle

Avoid dexamethasone in routine pediatric CAH management as hydrocortisone better mimics physiologic cortisol replacement and allows more precise dose titration 3, 6

Mineralocorticoid Replacement

Standard Fludrocortisone Dosing

• Recommended dose: 0.1-0.2 mg daily as a single morning dose for salt-losing CAH 7, 2
• FDA-approved dosing for salt-losing adrenogenital syndrome: 0.1-0.2 mg daily 2
• Children and younger adults may require higher doses (up to 500 μg daily) 8

Dose Adjustment Algorithm

Increase fludrocortisone when: 8, 7

• Hyponatremia (low sodium) is present
• Hyperkalemia (high potassium) develops
• Orthostatic hypotension occurs despite adequate sodium intake
• Persistent salt cravings continue

Decrease fludrocortisone (but never stop completely) when: 8, 7

• Hypertension develops
• Peripheral edema appears
• Supine hypertension is documented

Monitoring Parameters

• Blood pressure in supine and standing positions 8, 7
• Serum sodium and potassium levels 8, 7
• Body weight and clinical symptoms (salt cravings, lightheadedness, edema) 8
• Annual review minimum, with electrolytes checked at each visit 8, 7

Stress Dosing and Acute Management

Illness and Fever

• Double the oral glucocorticoid dose for 24 hours during febrile illness, then return to normal dose 1
• This recommendation is supported even with low-quality evidence due to life-threatening consequences of under-treatment 1

Adrenal Crisis Management

Immediate treatment protocol: 1

• Hydrocortisone 100 mg IV bolus immediately
• Follow with 100-300 mg/day as continuous infusion or 100 mg IV/IM every 6 hours
• Rapid isotonic saline infusion: 1 L over first hour, then 3-4 L total over 24-48 hours 1
• Do not delay treatment for diagnostic testing 1

Surgical Stress Dosing

• Major surgery: 100 mg hydrocortisone IM just before procedure, continue stress dosing until oral intake resumes 1, 7
• Minor procedures: Usually not required, but give extra 20 mg HC if symptoms develop 1
• Dental procedures: Extra morning dose 1 hour prior 1

Monitoring Treatment Adequacy

Clinical Assessment (Primary Method)

Plasma ACTH and serum cortisol are NOT useful for dose adjustment 1

Signs of over-replacement: 1

• Weight gain
• Insomnia
• Peripheral edema

Signs of under-replacement: 1

• Lethargy and fatigue
• Nausea and poor appetite
• Weight loss
• Increased or uneven pigmentation
• Salt cravings 8

Biochemical Monitoring

• Target 17-hydroxyprogesterone normalization in adults 4
• Serum electrolytes (sodium, potassium) for mineralocorticoid adequacy 8, 7
• Growth velocity and bone age in children 6, 9

Critical Safety Measures

Patient Education Requirements

• All patients must wear medical alert identification and carry a steroid emergency card 1, 8
• Training in intramuscular HC self-administration for emergencies 1
• Education on stress dose increases during illness, injury, or surgery 1

Common Pitfalls to Avoid

• Never stop fludrocortisone abruptly - can trigger life-threatening adrenal crisis with hypotension, hyponatremia, and hyperkalemia 8
• Never completely discontinue fludrocortisone for hypertension - reduce dose instead 8, 7
• Under-replacement with fludrocortisone is common and predisposes to recurrent adrenal crises 8
• Delays in emergency HC administration can be fatal 1

Drug Interactions Requiring Attention

• CYP3A4 inducers/inhibitors affect HC clearance and may require dose adjustment 1
• Avoid: Diuretics, acetazolamide, NSAIDs, potassium-containing salt substitutes, licorice, and grapefruit juice 8, 7
• Drospirenone-containing contraceptives may require higher fludrocortisone doses 8, 7

Dietary Recommendations

• Liberal salt and salty food intake encouraged 8, 7
• Avoid "healthy" potassium-containing salt substitutes 8

Special Populations

Pregnancy

• Small fludrocortisone dose adjustments may be needed, particularly in third trimester due to progesterone's anti-mineralocorticoid effects 8, 7

Non-Classical CAH

• Glucocorticoid therapy recommended only for: 9
  • Inappropriately early or rapidly progressing pubarche
  • Accelerated bone age progression in children
  • Overt virilization in adolescents
• Stress doses of HC recommended for major surgery, trauma, or childbirth only if suboptimal cortisol response to ACTH stimulation test 9