What is a normal cortisol level in the afternoon?

Normal Afternoon Cortisol Levels

Normal afternoon cortisol levels typically range from less than 1 to 11 μg/dL (approximately 28-303 nmol/L), with values progressively declining throughout the day from morning peaks. 1, 2

Physiological Context

Cortisol follows a distinct circadian rhythm with critical implications for interpretation:

• Morning levels peak between 6:00-8:00 AM at 3-19 μg/dL in healthy individuals 2
• Midday levels (11:00 AM-12:00 PM) drop to <1-11 μg/dL 2
• Afternoon levels (4:00-6:00 PM) further decline to <1-6 μg/dL 2
• Evening levels (7:00-8:00 PM) reach <1-4.5 μg/dL 2
• Late evening levels (10:00 PM) reach nadir at <1-2.9 μg/dL 2

The loss of this circadian rhythm is pathognomonic for Cushing's syndrome, where cortisol remains inappropriately elevated throughout the day and night. 2

Clinical Interpretation Pitfalls

A critical error in clinical practice is assuming cortisol is "normal" simply because it falls within the broad reference range for 8:00 AM or 5:00 PM samples. 3 This approach misses pathological elevations that occur during specific times in the 24-hour cycle, particularly in conditions with cyclic hypercortisolism. 3

Time-Dependent Reference Ranges

The afternoon cortisol must be interpreted based on the specific time of collection:

• A level of 10 μg/dL at 12:00 PM may be normal (upper limit ~11 μg/dL) 2
• The same 10 μg/dL at 6:00 PM is clearly elevated (normal upper limit ~6 μg/dL) 2
• Any level >6 μg/dL at 10:00 PM in adults warrants investigation for hypercortisolism 2

Factors Affecting Afternoon Cortisol

Several variables can alter afternoon cortisol measurements:

• Acute stress or illness temporarily elevates cortisol at any time of day 1
• Disrupted sleep patterns can shift the circadian rhythm 1
• CYP3A4-inducing medications (anticonvulsants, rifampin) increase cortisol clearance and may lower measured levels 4, 1
• Estrogen therapy increases cortisol-binding globulin (CBG), raising total cortisol but not free (biologically active) cortisol 5

When Afternoon Cortisol Testing Is Insufficient

Afternoon cortisol alone has limited diagnostic utility. Additional testing is warranted when:

• Clinical features of Cushing's syndrome are present despite normal afternoon cortisol—proceed to late-night salivary cortisol or 1 mg dexamethasone suppression test 1, 6
• Symptoms of adrenal insufficiency exist with borderline afternoon values—perform ACTH stimulation testing (morning cortisol >14 μg/dL rules out adrenal insufficiency, but lower values require dynamic testing) 1, 4
• Cyclic Cushing's syndrome is suspected—single measurements may miss hypercortisolemic phases; serial measurements over weeks are necessary 1, 4

Practical Algorithm for Afternoon Cortisol Interpretation

1. Document exact collection time (not just "afternoon")
2. Compare to time-specific reference ranges (not generic 8 AM/5 PM ranges) 2
3. If elevated for time of day: Measure late-night salivary cortisol or perform overnight dexamethasone suppression test 6, 2
4. If low with symptoms: Check morning cortisol and ACTH; consider ACTH stimulation test if morning cortisol <14 μg/dL 4, 1
5. If normal but high clinical suspicion: Repeat testing or measure 24-hour urinary free cortisol 4

The key principle: afternoon cortisol must never be interpreted in isolation but always in the context of time of collection, clinical presentation, and the patient's circadian rhythm pattern. 3, 2