Timing of Cortisol Draw for Adrenal Insufficiency
Cortisol should be drawn in the early morning, ideally between 8 AM and 12 PM, with the optimal time being around 8 AM when cortisol levels are physiologically at their peak. 1, 2
Rationale for Morning Timing
The morning timing is critical because cortisol follows a circadian rhythm with peak levels occurring in the early morning hours. 1 This physiological pattern makes morning samples the most reliable for diagnostic purposes:
- Morning cortisol (8 AM-12 PM) provides the highest diagnostic sensitivity for detecting adrenal insufficiency, as this is when cortisol levels should be at their maximum in healthy individuals 3
- A morning serum cortisol level serves as the first-line screening test before proceeding to dynamic testing 2, 4
Diagnostic Thresholds
When interpreting morning cortisol levels drawn between 8 AM and 12 PM:
- Cortisol <275 nmol/L (<10 μg/dL or <100 nmol/L in some studies) strongly suggests adrenal insufficiency and warrants further evaluation with ACTH stimulation testing 3, 5
- Cortisol >375 nmol/L (>13 μg/dL) reliably rules out adrenal insufficiency in most clinical contexts, making dynamic testing unnecessary 4, 5
- Intermediate values (275-375 nmol/L or 5-10 μg/dL) require ACTH stimulation testing for definitive diagnosis 2, 3
Complete Diagnostic Panel
When drawing morning cortisol, simultaneously obtain:
- ACTH level (also drawn in the morning) to distinguish primary from secondary adrenal insufficiency 1, 2
- Basic metabolic panel to assess for hyponatremia and hyperkalemia 1
- DHEAS level to support the diagnosis (low in primary adrenal insufficiency, low or low-normal in secondary) 2
Afternoon Sampling (When Morning Not Feasible)
If morning sampling is not possible in the outpatient setting:
- Afternoon samples (12 PM-6 PM) can be used with a lower threshold of <250 nmol/L to maintain 96% sensitivity for detecting adrenal insufficiency 3
- However, afternoon samples are less reliable for ruling out adrenal insufficiency due to the normal physiological decline in cortisol throughout the day 3
Critical Pitfall to Avoid
Do not draw cortisol levels in patients currently taking exogenous glucocorticoids (prednisone, hydrocortisone, dexamethasone) for other conditions, as these will suppress endogenous cortisol production and create iatrogenic secondary adrenal insufficiency, making interpretation impossible. 1 Laboratory confirmation should be deferred until glucocorticoid therapy can be safely discontinued with endocrine consultation. 1