The Healthy Diurnal Cortisol Curve
Cortisol normally peaks at waking and falls to a low midnight trough.
- ~18 µg/dL: Morning peak (~8 AM) (shortly after waking)
- ~2 µg/dL: Midnight trough (lowest point of the day)
- ~9:1: Peak-to-trough ratio (strong diurnal swing)
- SCN clock: Rhythm driver (entrained by light exposure)
Why cortisol rises and falls each day
Central clock sets a rising, then declining, cortisol pattern.
Clinical relevance of the normal baseline
This healthy curve is the reference standard for screening.
Autonomous Overproduction Erases the Rhythm
Excess, poorly-regulated cortisol secretion flattens the daily pattern.
- 3: Cause categories (pituitary, adrenal, ectopic)
- Elevated: Midnight cortisol (loses expected nocturnal dip)
- Impaired: Feedback control (source is often autonomous)
- Reduced: Daily amplitude (curve becomes flattened)
Sources of autonomous cortisol excess
Pituitary, adrenal, or ectopic tumors drive unregulated secretion.
Why the rhythm collapses first
Loss of nocturnal suppression often precedes overt symptoms.
The Midnight Cortisol Testing Window
Late-night salivary or serum cortisol maximizes diagnostic separation.
- Salivary / serum: Test type (late-night ~23:00–24:00)
- Very low: Normal expectation (near circadian trough)
- Inappropriately high: Cushing's expectation (no nocturnal suppression)
- High sensitivity: Diagnostic value (early, non-invasive screen)
Why midnight is the ideal sampling point
Curves diverge most at the normal nadir, near midnight.
Practical sampling considerations
Salivary sampling avoids the stress of venipuncture at night.
Overlaying Both 24-Hour Curves
Side-by-side curves show peak-trough rhythm vs. flattened elevation.
- Peak + trough: Normal pattern (clear diurnal variation)
- Flattened & high: Cushing's pattern (elevated through the night)
- ~Midnight: Best separation time (maximal curve divergence)
- Common: Daytime overlap (levels can look similar midday)
Reading the two overlaid curves
Daytime values overlap; nighttime values clearly separate.
Why single random draws mislead
A daytime-only sample can miss the diagnostic signal entirely.
A Simple, Sensitive Early Screening Clue
Elevated late-night cortisol flags Cushing's before further testing.
- First-line clue: Screening role (often precedes imaging/labs)
- Saliva or serum: Sample options (late-night collection)
- High specificity: Loss-of-rhythm sign (when trough is absent)
- Confirmatory testing: Next steps (dexamethasone suppression, imaging)
From rhythm loss to diagnosis
An elevated midnight value prompts confirmatory workup.
Value as an early, low-burden test
Simple sampling can precede more invasive procedures.
Loss of the midnight cortisol trough is one of the earliest, most accessible clues pointing toward Cushing's syndrome.