What is the fasting cortisol level that indicates adrenal insufficiency?

Fasting Cortisol Levels for Diagnosing Adrenal Insufficiency

A morning serum cortisol level <5 µg/dL (<138 nmol/L) is diagnostic of adrenal insufficiency, while a level >13 µg/dL (>358 nmol/L) reliably rules it out. 1, 2

Diagnostic Approach to Adrenal Insufficiency

Morning Cortisol Cutoffs

• <5 µg/dL (<138 nmol/L): Diagnostic of adrenal insufficiency 1
• 5-10 µg/dL (138-276 nmol/L): Intermediate values requiring further testing 1
• >13 µg/dL (>358 nmol/L): Reliably rules out adrenal insufficiency 2

Interpreting Intermediate Values

For patients with morning cortisol in the intermediate range (5-10 µg/dL), further testing is required:

• Cosyntropin Stimulation Test (CST): Gold standard confirmatory test
  • Standard dose: 250 μg IV/IM cosyntropin
  • Measure cortisol before and 60 minutes after administration
  • Normal response: Peak cortisol >18 μg/dL (>500 nmol/L) 1

Special Considerations

Critically Ill Patients

In critically ill patients, the American College of Critical Care Medicine recommends:

• Random total cortisol <276 nmol/L (10 µg/dL) suggests adrenal insufficiency 3
• Delta total serum cortisol <250 nmol/L (9 µg/dL) after ACTH administration indicates relative adrenal insufficiency 3

Patients with Cirrhosis

Patients with cirrhosis require special consideration due to altered protein binding:

• Standard cortisol measurements may overestimate adrenal insufficiency due to reduced cortisol binding globulin (CBG) and albumin 3
• Free cortisol measurements are more accurate but not routinely available:
  • Baseline free cortisol <50 nmol/L suggests adrenal insufficiency
  • Free cortisol <86 nmol/L after ACTH stimulation suggests adrenal insufficiency 3
• Salivary cortisol can be used as an alternative:
  • Baseline salivary cortisol <1.8 ng/ml (<0.18 µg/dl) suggests adrenal insufficiency
  • Increment <3 ng/ml (0.3 µg/dl) after ACTH stimulation suggests adrenal insufficiency 3

Differentiating Primary vs. Secondary Adrenal Insufficiency

Type	ACTH Level	Cortisol Level	Electrolytes	Hyperpigmentation
Primary	High	Low	↓Na, ↑K	Present
Secondary	Low	Low	Generally normal	Absent

4

Common Pitfalls and Caveats

1. Time of testing matters: Cortisol follows a diurnal rhythm, so samples should be collected in the early morning (approximately 8 AM) 1

2. Recent glucocorticoid use: Can suppress the HPA axis and lead to false results 1

3. Protein binding alterations: Conditions that affect cortisol binding proteins (cirrhosis, nephrotic syndrome, pregnancy) may affect total cortisol measurements 3

4. Medications that interfere with cortisol metabolism:

   • Anti-epilepsy medications, barbiturates, antituberculosis drugs may increase steroid metabolism
   • Grapefruit juice and licorice may decrease steroid metabolism 4

5. Acute stress: Can transiently elevate cortisol levels and mask underlying insufficiency

Remember that adrenal insufficiency is a potentially life-threatening condition, and patients with confirmed diagnosis require lifelong glucocorticoid replacement therapy (typically hydrocortisone 15-25 mg daily in divided doses) and education about stress dosing to prevent adrenal crisis 1.