How should adrenal insufficiency be treated, including glucocorticoid and mineralocorticoid replacement, acute crisis management, stress dosing, and follow‑up monitoring?

Treatment of Adrenal Insufficiency

All patients with adrenal insufficiency require daily glucocorticoid replacement with hydrocortisone 15-25 mg/day (or prednisone 3-5 mg/day), and those with primary adrenal insufficiency additionally need mineralocorticoid replacement with fludrocortisone 0.05-0.3 mg daily. 1

Chronic Maintenance Therapy

Glucocorticoid Replacement

Adults:

• Hydrocortisone 15-25 mg/day divided into 2-3 doses (preferred agent due to short half-life mimicking physiological cortisol rhythm) 1
• Alternative: Prednisone 3-5 mg/day in 1-2 divided doses 1
• Hydrocortisone remains the gold standard for glucocorticoid replacement 2

Children:

• Dosing based on body surface area: typically 8-15 mg/m²/day divided into multiple doses 3
• Doses exceeding 15-17 mg/m²/day in adolescents or 20 mg/m²/day in infants can cause growth suppression and shorter adult stature 3
• Monitor growth velocity, weight gain, and clinical well-being closely for dose adjustments 3

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Adults:

• Fludrocortisone 0.05-0.3 mg once daily in the morning 1
• Target: normotension, normokalemia, and plasma renin activity in the upper normal range 4

Children:

• Fludrocortisone 100 mcg (0.1 mg) daily 3
• Dose does NOT require adjustment by body surface area and often remains constant throughout life 3
• Infants (especially first 6 months): require additional sodium chloride supplementation of 1-2 g/day (17-34 mmol/day) divided across feedings due to mineralocorticoid resistance in immature kidneys 3

Monitoring Parameters

Glucocorticoid adequacy:

• Signs of under-replacement: inadequate weight gain, fatigue, anorexia, hyperpigmentation, salt craving 3
• Signs of over-replacement: weight gain, hypertension, growth suppression in children 3

Mineralocorticoid adequacy:

• Monitor blood pressure routinely 3
• Check plasma renin activity periodically, especially with clinical status changes 3
• Assess electrolytes (sodium, potassium) regularly 5
• Under-replacement: poor weight gain, salt craving, dehydration, hyponatremia with hyperkalemia, elevated plasma renin 3
• Over-replacement: hypertension and suppressed plasma renin 3

Pediatric follow-up:

• Infants require evaluation every 3-4 months minimum to assess growth, blood pressure, and general well-being 3
• Monitor blood pressure especially closely during the first year of life as mineralocorticoid sensitivity increases 3

Acute Adrenal Crisis Management

Adrenal crisis is a life-threatening emergency requiring immediate treatment without waiting for laboratory confirmation. 3

Immediate Treatment (First Hour)

Adults:

• Hydrocortisone 100 mg IV bolus immediately 3, 2
• Rapid infusion of 1000 mL isotonic saline (0.9% NaCl) within the first hour, or 5% glucose in isotonic saline 3
• Continue with hydrocortisone 200 mg/24 hours as continuous IV infusion (preferred) or 50 mg IV every 6 hours 3, 5

Children:

• Hydrocortisone 50-100 mg/m² IV or IM bolus immediately 3, 2
  • Weight-based dosing: <15 kg (0-2 years): 25 mg; 15-25 kg (2-6 years): 50 mg; >25 kg (>6 years): 100 mg 2
• Rapid bolus of 0.9% NaCl 20 mL/kg (can repeat up to total of 60 mL/kg if shocked) 3, 2
• Maintenance: Hydrocortisone 50-100 mg/m²/24 hours divided every 6 hours or as continuous infusion at 2-3 mg/m²/hour 2

Alternative Glucocorticoids (if hydrocortisone unavailable)

• Prednisolone is the preferred alternative 3
• Dexamethasone is the least-preferred option and should only be used if no other glucocorticoid is available 3

Supportive Care

• Check blood glucose hourly; if <3.5 mmol/L (63 mg/dL), give 2-5 mL/kg of 10% glucose in children 2
• Monitor and correct hyponatremia and hyperkalemia 3, 2
• Monitor blood pressure and cardiac function 2
• Fludrocortisone is NOT required acutely when high-dose hydrocortisone is given (hydrocortisone has mineralocorticoid activity at high doses) 2

Transition to Oral Therapy

• Continue IV hydrocortisone until patient is hemodynamically stable and able to tolerate oral intake 5
• Reduce to hydrocortisone 100 mg/day on the following day, then gradually taper 3
• In children, start oral regimen with hydrocortisone 30-50 mg/m²/24 hours, then gradually reduce to maintenance level 2
• Resume fludrocortisone 0.05-0.1 mg daily once oral intake established (primary adrenal insufficiency only) 2

Stress Dosing (Sick Day Rules)

Home Management of Illness

Fever requiring bed rest:

• Double oral hydrocortisone dose for temperature 38°C 3, 2
• Triple oral hydrocortisone dose for temperature ≥39°C 3, 2
• Continue increased dose until recovery (usually 2-3 days) 3
• Increase consumption of electrolyte-containing fluids 3

Vomiting/diarrhea or inability to take oral medication:

• Adults: Hydrocortisone 100 mg IM or SC immediately 3, 2
• Children: Hydrocortisone 50 mg/m² IM (infants 25 mg, school-age 50 mg, adolescents 100 mg) 3
• Go to hospital and consult endocrinologist 2

Surgical Stress Dosing

Major surgery with general anesthesia:

• Hydrocortisone 100 mg IV bolus at induction 3, 2, 5
• Continuous IV infusion of 200 mg/24 hours (or 50 mg IV every 6 hours) 3, 2, 5
• Continue IV therapy while nil-by-mouth or experiencing postoperative nausea/vomiting 2
• In children: hydrocortisone 50-100 mg/m²/day divided every 6 hours 3

Minor to moderate surgical stress:

• Hydrocortisone 25-75 mg/24 hours (usually 1-2 days) 3
• In children: hydrocortisone 50 mg/m² IM or double/triple replacement doses 3

Cesarean section:

• Hydrocortisone 100 mg IV at start of procedure 2
• Double enteral hydrocortisone dose for 48 hours to 1 week postoperatively (24 hours if rapid recovery) 2

Labor and vaginal delivery:

• Hydrocortisone 100 mg IV at onset of labor 2
• Double oral hydrocortisone doses for 24 hours after delivery 2

Dental procedures:

• Extra morning dose 1 hour before surgery (10 mg hydrocortisone) 2
• Double oral dose for 24 hours, then return to normal dose 2

Duration and Tapering of Stress Dosing

• After >48-72 hours of high-dose therapy, taper gradually rather than stopping abruptly 5
• After >14 days of glucocorticoid exposure, a gradual taper is mandatory to prevent adrenal crisis 5
• Typical course in septic shock: 7-14 days 5

Patient Education and Emergency Preparedness

All patients with adrenal insufficiency must be equipped with:

• Emergency card (European steroid emergency card or equivalent) carried at all times 2
• Emergency injection kit with hydrocortisone 100 mg for IM self-injection 2, 6
• Medical alert bracelet or necklace indicating diagnosis and need for hydrocortisone 6
• Adequate supply of medication at all times 2

Patients and families must be trained on:

• Recognizing signs of adrenal crisis (hypotension, severe fatigue, nausea/vomiting, altered mental status, hyponatremia, hypoglycemia) 2, 6
• When and how to increase glucocorticoid doses during stress 6
• How to perform IM self-injection of hydrocortisone 6
• Conditions that increase cortisol requirements (fever, infection, trauma, surgery) 6

Common Pitfalls and Caveats

• Never delay treatment of suspected adrenal crisis while waiting for laboratory confirmation—give hydrocortisone immediately 3
• Continuous IV infusion of hydrocortisone is preferred over intermittent boluses during major stress, as it maintains more consistent cortisol levels in the physiological stress range 7
• Do not use corticosteroids in sepsis without shock—no mortality benefit has been demonstrated 5
• Avoid corticosteroids in influenza infection—observational data suggest increased mortality (OR ≈3.1) and higher risk of superinfection 5
• Glucocorticoid-induced adrenal insufficiency is common and underdiagnosed—suspect in any patient who has recently tapered or discontinued supraphysiological glucocorticoid doses 1, 8
• Mineralocorticoid replacement is often inadequate—many patients with primary adrenal insufficiency remain symptomatic with salt craving and postural dizziness despite treatment, suggesting under-replacement 4
• Growth monitoring is critical in children—doses exceeding physiological range can cause permanent height loss 3