What tests can be drawn to check for adrenal stress response in a patient with a history of chronic diseases such as diabetes, hypertension, or chronic obstructive pulmonary disease (COPD) and currently taking medications like steroids?

Testing for Adrenal Stress Response

In patients with chronic diseases taking steroids, measure an 8 AM cortisol level first—if below 500 nmol/L (approximately 18 μg/dL), proceed with a low-dose (1 μg) ACTH stimulation test to assess adrenocortical reserve, as this is more sensitive than the standard 250 μg test for detecting central adrenal insufficiency. 1

Initial Screening Approach

Morning Cortisol Level

• Draw blood at 8:00 AM after the patient has been out of bed for at least 2 hours to capture the physiologic cortisol peak 2
• A cortisol level below 200 nmol/L (7.2 μg/dL) strongly suggests adrenal insufficiency, while levels above 500 nmol/L (18 μg/dL) generally indicate adequate adrenal function 3
• Values between 200-500 nmol/L require further testing with ACTH stimulation 3

Critical Consideration for Steroid Users

• If the patient is currently taking exogenous corticosteroids (prednisone, dexamethasone, etc.), the morning cortisol will be suppressed and cannot be used to assess endogenous adrenal function 4
• Hydrocortisone must be held for 24 hours before testing, while other synthetic steroids require longer washout periods 4
• Consider using dexamethasone temporarily if testing is needed urgently, as it does not interfere with cortisol assays 5

ACTH Stimulation Testing

Low-Dose vs Standard-Dose Test

• The 1 μg ACTH stimulation test is significantly more sensitive than the conventional 250 μg test for detecting central (secondary) adrenal insufficiency, with better performance compared to the gold standard insulin tolerance test 1
• The 250 μg dose is supraphysiological and can transiently stimulate adrenal cortex even in patients with documented central adrenal insufficiency, leading to false-negative results 1
• However, the high-dose (250 μg) test remains preferred in clinical practice because the low-dose test has not been fully validated and is not commercially available in 1 μg vials 5

Test Interpretation

• A peak cortisol level below 500 nmol/L (18 μg/dL) at 30 minutes after ACTH administration indicates impaired adrenocortical reserve 1, 3
• Some protocols also require an incremental rise of at least 200 nmol/L (7.2 μg/dL) from baseline 3
• The test should not be used if recent pituitary injury is suspected, as adrenal reserve declines slowly after loss of pituitary stimulation 4

Additional Laboratory Tests

Plasma ACTH and Renin-Aldosterone

• Measure plasma ACTH simultaneously with morning cortisol to distinguish primary from secondary adrenal insufficiency 6
• In primary adrenal insufficiency, ACTH is markedly elevated (>100 pg/mL) with low cortisol 6
• In secondary adrenal insufficiency (from chronic steroid use or pituitary disease), both ACTH and cortisol are low 4
• Plasma renin activity (PRA) and aldosterone should be measured if primary adrenal insufficiency is suspected, as these are elevated in 100% of primary cases 6

Electrolytes

• Check serum sodium and potassium, as hyponatremia and hyperkalemia are important diagnostic clues for adrenal insufficiency 5
• These findings are refractory to standard treatment and suggest mineralocorticoid deficiency 5

Special Populations

Critically Ill Patients

• In critically ill patients with septic shock requiring vasopressors, measure a random cortisol level rather than waiting for morning 7, 5
• A random cortisol below 10 μg/dL in patients with low cortisol-binding proteins, or below 15 μg/dL in those with near-normal binding proteins, suggests adrenal insufficiency 7
• Free cortisol levels (>1.8 μg/dL is normal) offer advantages over total cortisol in critically ill patients with low binding proteins 7
• Consider empiric hydrocortisone 200-300 mg/day in divided doses for septic shock patients who are pressor-dependent, regardless of cortisol levels 5

Patients on Chronic Steroids

• Patients receiving corticosteroids for other conditions (COPD, autoimmune diseases) are at high risk for HPA axis suppression 4
• The HPA axis should be tested for recovery after 3 months of maintenance hydrocortisone therapy in patients with isolated central adrenal insufficiency from prior steroid use 4
• All patients need education on stress dosing (doubling or tripling maintenance dose during illness), use of emergency injectable steroids, and when to seek medical attention for impending adrenal crisis 4

Common Pitfalls to Avoid

• Do not rely solely on the presence or absence of symptoms, as manifestations are nonspecific (fatigue, weakness, hypotension) 5
• Do not attempt laboratory confirmation in patients currently on high-dose corticosteroids for other conditions until treatment is ready to be discontinued 4
• Do not use the ACTH stimulation test immediately after acute pituitary injury, as it can give false-negative results early in the course 4
• Ensure potassium repletion before testing, as hypokalemia can suppress cortisol production 2