How to manage adrenal insufficiency in a patient with a history of chronic steroid use, such as asthma or rheumatoid arthritis?

Managing Adrenal Insufficiency in Patients with Chronic Steroid Use

For patients with asthma or rheumatoid arthritis on chronic steroids, immediately assess clinical severity and initiate physiologic hydrocortisone replacement at 15-25 mg daily in divided doses, combined with comprehensive stress-dosing education and emergency management protocols. 1

Immediate Assessment and Risk Stratification

Recognize High-Risk Scenarios

• Any patient taking ≥20 mg/day prednisone or equivalent for ≥3 weeks who develops unexplained hypotension should be presumed to have adrenal insufficiency until proven otherwise. 2
• HPA axis suppression should be anticipated in patients receiving >7.5 mg prednisolone equivalent daily for >3 weeks, with approximately 39-48% developing adrenal insufficiency. 3
• Even doses as low as 5 mg prednisolone daily for >1 month can cause adrenal suppression in a significant proportion of adults. 3
• Inhaled corticosteroids at commonly prescribed doses can suppress the adrenal response to ACTH in a dose-dependent manner, placing these patients at risk for adrenal crisis. 4

Clinical Presentation to Recognize

• Unexplained collapse, hypotension, and gastrointestinal symptoms (vomiting or diarrhea) should immediately raise suspicion for adrenal crisis. 2
• Morning nausea, lack of appetite, lethargy, poor appetite, weight loss, and fatigue are common symptoms representing glucocorticoid under-replacement. 2
• Do not rely on electrolyte abnormalities alone—hyponatremia is present in 90% of cases, but hyperkalemia occurs in only ~50% of cases. 2

Treatment Based on Clinical Severity

Severe/Life-Threatening Adrenal Crisis

Treatment should NEVER be delayed for diagnostic procedures. 2, 1

• Give IV hydrocortisone 100 mg bolus immediately, followed by 100-300 mg/day as continuous infusion or 100 mg every 6-8 hours. 1
• Aggressive fluid resuscitation with 3-4 L isotonic saline at initial rate of 1 L/hour with frequent hemodynamic monitoring. 1
• Hospitalization is required immediately. 1
• Taper parenteral steroids over 1-3 days to oral maintenance once stabilized. 1

Moderate Symptoms

• Start hydrocortisone at 2-3 times maintenance dose (approximately 30-50 mg daily). 1
• Taper to physiologic maintenance (15-25 mg daily) over 5-10 days as symptoms improve. 1

Mild Symptoms or Stable Patients

• Begin physiologic replacement with hydrocortisone 15-25 mg daily in split doses. 1
• Optimal dosing schedule: 10 mg at 7:00 AM, 5 mg at 12:00 PM, and 2.5-5 mg at 4:00 PM to approximate physiological cortisol secretion. 2
• First dose should be taken immediately upon waking, and last dose at least 6 hours before bedtime to mimic natural cortisol rhythm. 1
• Alternative effective regimens include 15+5 mg, 10+10 mg, or 10+5+5 mg depending on individual response. 2

Critical Patient Education Requirements

All patients must receive comprehensive education on the following: 1

Stress-Dosing Protocol

• Double or triple the dose during illness, fever, or physical stress. 2
• For minor stress: double the usual daily dose for 1-2 days. 2
• For moderate stress: hydrocortisone 50-75 mg daily. 2
• For major stress/surgery: hydrocortisone 100-150 mg daily. 2

Emergency Supplies and Identification

• Prescribe hydrocortisone 100 mg IM injection kit with self-injection training. 2
• Patient must wear medical alert bracelet or necklace indicating adrenal insufficiency to trigger stress-dose corticosteroids by emergency personnel. 2, 1
• Carry adequate supply of medication for emergencies. 4

Warning Signs of Adrenal Crisis

• Severe weakness, confusion, abdominal pain, hypotension, severe vomiting and/or diarrhea. 2, 1

Surgical and Procedural Management

Major Surgery

• 100 mg hydrocortisone IM just before anesthesia. 1
• Continue stress-dose coverage perioperatively. 4

Minor Surgery or Major Dental Procedures

• 100 mg hydrocortisone IM before procedure. 1
• Double the oral dose for 24 hours. 1

Minor Procedures Requiring General Anesthesia

• Hydrocortisone 2 mg/kg IV or IM at induction of anesthesia. 4
• Double normal hydrocortisone doses once enteral feeding established, continue on double doses for 24 hours. 4

Minor Procedures NOT Requiring General Anesthesia

• Double morning dose of hydrocortisone given pre-operatively. 4

Diagnostic Testing Considerations

When to Test

Laboratory confirmation of adrenal insufficiency cannot be performed during active corticosteroid treatment. 1

• Wait 48 hours after stopping prednisolone before performing cosyntropin stimulation test to allow accurate cortisol measurement. 3
• For patients on chronic prednisolone who cannot safely stop for 48 hours, consider empiric glucocorticoid replacement and defer definitive testing for 3 months after switching to physiologic hydrocortisone. 3

Testing Protocol

• Standard cosyntropin stimulation test: 0.25 mg (250 mcg) IV or IM with cortisol measured at 30 and/or 60 minutes. 2
• Peak cortisol <500 nmol/L (<18 mcg/dL) confirms adrenal insufficiency. 2, 3
• Peak cortisol >550 nmol/L (>18-20 mcg/dL) excludes adrenal insufficiency. 2

Important Testing Pitfalls

• Never attempt diagnostic testing while patient is actively taking prednisolone—morning cortisol will be falsely low due to iatrogenic secondary adrenal insufficiency. 3
• If patient is acutely ill or unstable, immediately treat with IV hydrocortisone 100 mg without waiting for testing. 3
• Exogenous steroids, including dexamethasone, can suppress the HPA axis and confound adrenal testing. 2

Special Considerations for Primary vs. Secondary Adrenal Insufficiency

Primary Adrenal Insufficiency (Addison's Disease)

• Requires both glucocorticoid AND mineralocorticoid replacement. 2
• Add fludrocortisone 0.05-0.1 mg daily (typical range 50-200 µg daily, up to 500 µg in younger adults). 2, 1
• Monitor for adequacy by assessing salt cravings, orthostatic blood pressure, and peripheral edema. 2
• Unrestricted sodium salt intake is essential. 2

Secondary Adrenal Insufficiency (from Chronic Steroid Use)

• Only requires glucocorticoid replacement since renin-angiotensin-aldosterone system remains intact. 2
• Characterized by low cortisol with low or inappropriately normal ACTH. 2

Monitoring and Follow-Up

Regular Monitoring

• Assess weight, blood pressure, and serum electrolytes at least annually. 1
• Monitor for clinical improvement of fatigue, nausea, abdominal pain, and hypotension. 1
• Schedule follow-up in 2-4 weeks to reassess symptoms and adjust medication. 1

Annual Screening for Associated Conditions

• Thyroid function, diabetes, vitamin B12 deficiency. 2
• Patients with frequent or episodic diarrhea should be screened for celiac disease. 2

Critical Pitfalls to Avoid

• Never delay treatment of suspected acute adrenal crisis for diagnostic procedures—mortality is high if untreated. 2
• Do not rely solely on electrolyte abnormalities for diagnosis. 2
• When treating concurrent hypothyroidism and adrenal insufficiency, start corticosteroids several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis. 2, 1
• Avoid abrupt discontinuation of corticosteroids—taper gradually to minimize withdrawal symptoms and adrenal insufficiency. 5, 6
• Be aware of drug interactions: amphotericin B, potassium-depleting diuretics, digitalis glycosides, and macrolide antibiotics can interact adversely with corticosteroids. 5, 6

Assessing Recovery of HPA Axis Function

• After 3 months on stable hydrocortisone maintenance therapy, perform ACTH stimulation testing to assess HPA axis recovery. 3
• Recovery of adrenal function varies greatly amongst individuals and may take up to 12 months after discontinuation of therapy. 6, 7
• Endocrinology consultation is recommended for establishing a recovery and weaning protocol. 1