Biomarker
Cortisol (4-Point Salivary)
Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
Observational— Cohort-validated diurnal slope predicts mortality
What the 4-point test captures
- Cortisol awakening response (CAR): the surge 30–45 min after waking; absent or blunted CAR associates with chronic stress, burnout, depression, and post-trauma states.
- Diurnal slope: how steeply cortisol falls from morning peak to evening trough; flat slope predicts mortality in multiple cohorts.
- Bedtime cortisol: elevation suggests stress, sleep disturbance, or Cushing’s.
Why salivary vs. serum
Saliva measures free (unbound) cortisol — the biologically active fraction. It avoids needle-stick stress affecting the measurement. Useful for at-home collection across the day.
When to consider
- Suspected adrenal insufficiency (with morning serum cortisol).
- Cushing’s evaluation (bedtime salivary is screening test).
- Burnout, chronic fatigue, persistent insomnia evaluation.
- Functional medicine / longevity practice context.
Cautions
- Cortisol is highly modifiable — recent stress, illness, exercise, meals, caffeine, alcohol all affect it.
- "Adrenal fatigue" is not a clinically validated diagnosis; flat slopes reflect dysregulation but the term itself lacks endocrine standing.
- Single tests have high variability; repeat over multiple days for baseline.
Related entries
References
- Adam, E. K. et al. Diurnal cortisol slopes and mental and physical health outcomes: a systematic review and meta-analysis. Psychoneuroendocrinology 83, 25–41 (2017).