Why are corticosteroids (cortisol replacement therapy) prescribed for adrenal insufficiency, and do I have this condition?

Understanding Corticosteroid Replacement in Adrenal Insufficiency

Corticosteroids are prescribed for adrenal insufficiency because your adrenal glands cannot produce adequate cortisol—a hormone essential for life—and without replacement therapy, you risk life-threatening adrenal crisis. 1

Why Corticosteroids Are Necessary

Your body requires cortisol for fundamental survival functions including blood pressure regulation, immune response modulation, glucose metabolism, and stress response. 2 When the adrenal glands fail to produce sufficient cortisol (adrenal insufficiency), external replacement becomes medically necessary to prevent:

• Adrenal crisis: A life-threatening emergency causing severe hypotension, shock, altered mental status, and death if untreated 3
• Chronic symptoms: Debilitating fatigue (50-95% of patients), nausea and vomiting (20-62%), weight loss (43-73%), and inability to respond to physical stress 3
• Metabolic collapse: Inability to maintain blood pressure, blood sugar, and electrolyte balance during illness or stress 1

Important distinction: "Adrenal fatigue" is not a recognized medical diagnosis. 3 The correct term is adrenal insufficiency, which is a serious, objectively diagnosed endocrine disorder—not a vague syndrome of tiredness.

Do You Have Adrenal Insufficiency?

Adrenal insufficiency requires specific diagnostic testing and cannot be self-diagnosed. Here's the algorithmic approach:

Step 1: Assess Your Risk Factors

High-risk scenarios requiring immediate evaluation: 4, 3

• Currently taking or recently stopped ≥20 mg prednisone daily (or equivalent) for ≥3 weeks 4
• Taking 5-20 mg prednisone daily for extended periods (30-50% develop adrenal insufficiency) 4
• Using high-dose inhaled corticosteroids like fluticasone (can cause adrenal insufficiency even at standard doses) 5
• History of pituitary tumor, surgery, or radiation 1, 4
• Autoimmune conditions (thyroid disease, type 1 diabetes, vitiligo) 1
• Unexplained hypotension requiring vasopressors 4

Step 2: Recognize Diagnostic Symptoms

Classic presentation includes: 3, 4

• Persistent fatigue unrelieved by rest
• Unexplained weight loss with poor appetite
• Nausea, especially in the morning 4
• Salt cravings (suggests primary adrenal insufficiency) 4
• Orthostatic hypotension (dizziness when standing) 1
• Hyperpigmentation of skin (primary adrenal insufficiency only) 4

Critical warning: These symptoms are nonspecific and overlap with many conditions. 3 Testing is mandatory for diagnosis.

Step 3: Obtain Diagnostic Testing

Initial laboratory workup: 4, 3

• Morning (8 AM) serum cortisol and ACTH: First-line test 4, 3

  • Cortisol <5 µg/dL (<140 nmol/L) with high ACTH = primary adrenal insufficiency 3, 4
  • Cortisol 5-10 µg/dL (140-275 nmol/L) with low/normal ACTH = secondary adrenal insufficiency 3, 4
  • Cortisol >18-20 µg/dL (>500-550 nmol/L) = adrenal insufficiency excluded 4

• Electrolytes: Check sodium and potassium 4

  • Hyponatremia present in 90% of new diagnoses 4
  • Hyperkalemia only in ~50% of primary cases 4

Confirmatory testing when morning cortisol is indeterminate (5-18 µg/dL): 4, 3

• ACTH stimulation test (cosyntropin test): Gold standard 4, 3
  • Administer 250 mcg cosyntropin IV or IM 4
  • Measure cortisol at baseline, 30, and 60 minutes 4
  • Peak cortisol <18 µg/dL (<500 nmol/L) = adrenal insufficiency confirmed 4, 3
  • Peak cortisol >18-20 µg/dL (>500-550 nmol/L) = normal response 4

Step 4: Determine the Type and Cause

Primary adrenal insufficiency (Addison's disease): 4, 3

• Low cortisol + high ACTH + low DHEAS 3
• Measure 21-hydroxylase autoantibodies (positive in ~85% of autoimmune cases) 4
• If antibodies negative, obtain adrenal CT to evaluate for hemorrhage, tuberculosis, metastases 4

Secondary adrenal insufficiency: 4, 3

• Low cortisol + low/normal ACTH + low DHEAS 3
• Consider pituitary MRI if multiple hormone deficiencies or headaches/vision changes 1

Glucocorticoid-induced adrenal insufficiency: 3, 6

• Most common form of adrenal insufficiency 3
• Caused by exogenous steroid suppression of the HPA axis 6
• Diagnosis requires stopping steroids and retesting after 3 months, or empiric treatment with reassessment 4

Treatment: Why and How Corticosteroids Are Used

Maintenance Replacement Therapy

For confirmed adrenal insufficiency, lifelong glucocorticoid replacement is mandatory: 1, 3

Glucocorticoid options: 1, 3

• Hydrocortisone 15-25 mg daily in divided doses (preferred): 10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM 1
• Prednisone 3-5 mg daily as single morning dose (alternative) 3, 4
• Cortisone acetate 25-37.5 mg daily in divided doses (alternative) 1

For primary adrenal insufficiency, add mineralocorticoid replacement: 1, 3

• Fludrocortisone 0.05-0.2 mg daily (typical range 50-200 mcg, may need up to 500 mcg in young adults) 1, 4
• Monitor for adequacy by assessing salt cravings, orthostatic blood pressure, and peripheral edema 1

Stress Dosing: Critical for Survival

All patients must learn to increase doses during illness, injury, or stress: 1

• Minor stress (mild cold, dental work): Double usual daily dose for 1-2 days 4
• Moderate stress (fever, gastroenteritis): Hydrocortisone 50-75 mg daily or prednisone 20 mg daily 4
• Major stress (surgery, severe illness): Hydrocortisone 100-150 mg daily IV/IM 1, 4

Emergency Management of Adrenal Crisis

If suspected adrenal crisis (severe hypotension, vomiting, altered mental status), treatment must NEVER be delayed for testing: 1, 4, 7

1. Hydrocortisone 100 mg IV bolus immediately 7
2. Rapid IV saline infusion: 1 L over first hour, then 2-3 L additional 7
3. Continue hydrocortisone 50-100 mg IV every 6-8 hours for first 24 hours 7
4. Taper over 5-7 days to oral maintenance once stable 7

Mandatory Patient Education

Every patient with adrenal insufficiency requires: 1, 4

• Medical alert bracelet or necklace stating "adrenal insufficiency" 1, 4
• Emergency injectable hydrocortisone 100 mg IM kit with self-injection training 4, 7
• Written stress-dosing instructions for sick days 1, 4
• Endocrinology consultation for ongoing management 1, 4

Critical Pitfalls to Avoid

Never assume you have adrenal insufficiency without proper testing—symptoms are nonspecific and many conditions cause similar complaints. 3

Never stop corticosteroids abruptly if you've been taking them long-term—this can precipitate life-threatening adrenal crisis. 4, 6

Never delay emergency treatment for suspected adrenal crisis to obtain diagnostic tests—mortality is high if untreated. 1, 4, 7

Do not rely on electrolyte abnormalities alone—10-20% of patients have normal electrolytes at presentation. 4

Recognize that "adrenal fatigue" is not adrenal insufficiency—the former is not a recognized medical diagnosis, while the latter is a serious, life-threatening condition requiring objective testing and lifelong treatment. 3

If you suspect you have adrenal insufficiency based on symptoms or risk factors, seek immediate evaluation with morning cortisol and ACTH testing from an endocrinologist or your primary care physician. 4, 3