At what cortisol level is concern warranted for adrenal insufficiency?

Diagnosing Adrenal Insufficiency: Cortisol Level Thresholds

A random plasma cortisol level below 10 μg/dL (276 nmol/L) or a delta cortisol less than 9 μg/dL after cosyntropin stimulation warrants concern for adrenal insufficiency in critically ill patients. 1

Diagnostic Thresholds for Adrenal Insufficiency

Random Cortisol Measurements

• A random total cortisol level below 10 μg/dL (276 nmol/L) is suggestive of adrenal insufficiency in critically ill patients 1
• Morning cortisol levels below 5 μg/dL (138 nmol/L) strongly indicate adrenal insufficiency and further testing may not be necessary 2
• Morning cortisol levels above 10 μg/dL (276 nmol/L) make adrenal insufficiency unlikely (only 1.2% of patients with levels ≥10 μg/dL have confirmed adrenal insufficiency) 2

Cosyntropin Stimulation Testing

• A delta cortisol (change from baseline) less than 9 μg/dL after 250 μg cosyntropin administration suggests adrenal insufficiency 1
• Peak cortisol below 18 μg/dL (500 nmol/L) after stimulation is diagnostic of primary adrenal insufficiency according to Endocrine Society guidelines 1, 3
• With newer, more specific cortisol assays, the threshold may need to be adjusted to approximately 13 μg/dL (368 nmol/L) 4

Special Considerations for Different Patient Populations

Critically Ill Patients

• The American College of Critical Care Medicine recommends using either a random total cortisol <10 μg/dL or a delta cortisol <9 μg/dL after ACTH stimulation to diagnose Critical Illness-Related Corticosteroid Insufficiency (CIRCI) 1
• In patients with cirrhosis, these same thresholds apply, though free cortisol measurements may be more accurate due to reduced binding protein levels 1

Patients with Hyponatremia

• Adrenal insufficiency must be excluded in patients with hypo-osmolar hyponatremia as it can mimic SIADH 3
• The standard 0.25 mg cosyntropin stimulation test with cortisol measurements at baseline and 30 minutes post-administration is necessary in these cases 3

Non-critically Ill Patients

• Morning cortisol <3.5 μg/dL (98 nmol/L) is highly specific for adrenal insufficiency 5
• Morning cortisol >10.3 μg/dL (285 nmol/L) has 100% sensitivity for ruling out adrenal insufficiency 5
• For intermediate values, stimulation testing is recommended 5

Combined Testing Approaches

• Using both baseline cortisol and DHEAS measurements can improve diagnostic accuracy 2
• Among patients with baseline cortisol between 5-9.9 μg/dL, only 1.3% had adrenal insufficiency if DHEAS was ≥60 μg/dL 2
• The majority (72.2%) of patients with both baseline cortisol <5 μg/dL and DHEAS <25 μg/dL were found to have adrenal insufficiency 2

Pitfalls and Caveats

• Assay variability significantly impacts cortisol measurements - newer assays tend to report lower values than older ones 4
• Patients on exogenous steroids may have falsely low cortisol levels due to suppression of the HPA axis 3
• Low serum binding proteins (as seen in cirrhosis or critical illness) may lead to falsely low total cortisol measurements despite adequate free cortisol levels 1
• Treatment should never be delayed for diagnostic procedures if adrenal crisis is suspected clinically 1, 3
• Time of day affects cortisol levels, with morning levels typically being higher, though this effect is less pronounced in critically ill patients 2