What cortisol level indicates adrenal insufficiency?

Cortisol Levels Indicating Adrenal Insufficiency

A morning serum cortisol level <250 nmol/L (9 μg/dL) with elevated ACTH is diagnostic of primary adrenal insufficiency, while a level <400 nmol/L (14.5 μg/dL) with elevated ACTH raises strong suspicion requiring further evaluation. 1

Diagnostic Approach to Adrenal Insufficiency

Initial Laboratory Assessment

• Morning cortisol measurement: Ideally collected around 8 AM

  • <250 nmol/L (<9 μg/dL) with elevated ACTH: Diagnostic of primary adrenal insufficiency 1
  • <400 nmol/L (<14.5 μg/dL) with elevated ACTH: Strong suspicion of primary adrenal insufficiency 1
  • <83 nmol/L (<3 μg/dL): Previously thought to be diagnostic, but recent evidence shows this is not reliable in hospitalized patients 2

• ACTH level: Critical to differentiate primary from secondary adrenal insufficiency

  • High ACTH + low cortisol = Primary adrenal insufficiency 1
  • Low/normal ACTH + low cortisol = Secondary adrenal insufficiency 1

• Basic metabolic panel: Look for:

  • Hyponatremia (present in 90% of new cases) 1
  • Hyperkalemia (present in ~50% of cases) 1
  • Hypoglycemia (more common in children) 1

Confirmatory Testing

• ACTH stimulation test: Gold standard for equivocal cases
  • Administer 0.25 mg synthetic ACTH (cosyntropin) IV or IM
  • Measure cortisol at baseline and 30-60 minutes post-administration
  • Peak cortisol <500 nmol/L (<18 μg/dL) confirms adrenal insufficiency 1
  • Using newer cortisol assays, a cutoff of <405 nmol/L (<14.7 μg/dL) may be more appropriate 2

Clinical Pearls and Pitfalls

Important Considerations

1. Never delay treatment of suspected acute adrenal insufficiency for diagnostic testing 1

   • If adrenal crisis is suspected, administer hydrocortisone 100 mg IV immediately

2. Cortisol levels can be misleading in certain situations:

   • Approximately 10% of patients with primary adrenal insufficiency may present with normal cortisol levels 3
   • Stress, acute illness, or sepsis can elevate cortisol, masking underlying insufficiency 1
   • Exogenous steroid use (including inhaled steroids) can affect interpretation 1

3. Morning cortisol thresholds:

   • 375 nmol/L (>13.6 μg/dL): Likely rules out adrenal insufficiency with 95% specificity 4

   • <236 nmol/L (<8.5 μg/dL): Suggests adrenal insufficiency with 84% sensitivity and 71% specificity 4
   • For patients with known pituitary disease, a threshold of >330 nmol/L (>12 μg/dL) gives 95% specificity 4

Additional Laboratory Findings in Primary Adrenal Insufficiency

• Increased plasma renin activity
• Low aldosterone levels
• Low DHEAS (dehydroepiandrosterone sulfate) levels 5
• TSH may be mildly elevated (4-10 IU/L) due to lack of cortisol's inhibitory effect 1

Management Implications of Diagnosis

Once adrenal insufficiency is confirmed, treatment should be initiated promptly:

• Primary adrenal insufficiency:

  • Glucocorticoid replacement: Hydrocortisone 15-25 mg daily in divided doses 5
  • Mineralocorticoid replacement: Fludrocortisone 50-200 μg daily 1

• Secondary adrenal insufficiency:

  • Glucocorticoid replacement only (mineralocorticoid not needed)
  • Address underlying pituitary condition 1

• All patients need:

  • Education on stress dosing
  • Medical alert identification
  • Emergency injectable hydrocortisone 1, 5

Remember that early diagnosis and proper management are critical to prevent life-threatening adrenal crisis, which carries significant morbidity and mortality.