Cortisol

Overview

Cortisol is a glucocorticoid hormone produced by the adrenal cortex that helps regulate metabolism, immune responses, blood pressure, and the body’s stress response. It is secreted in a diurnal pattern, with peak levels in the early morning and a nadir around midnight. Elevated levels may indicate Cushing syndrome, chronic stress, depression, or exogenous glucocorticoid use, whereas low levels suggest adrenal insufficiency or hypopituitarism. Measuring cortisol is clinically useful for diagnosing disorders of the hypothalamic–pituitary–adrenal (HPA) axis and monitoring glucocorticoid therapy.

Clinical Use Cases

  • Diagnosing adrenal insufficiency (e.g., Addison disease, secondary adrenal insufficiency).
  • Evaluating hypercortisolism (Cushing syndrome) using serum, urine, or salivary tests.
  • Monitoring response to glucocorticoid replacement or suppression therapy.
  • Assessing HPA axis function with dynamic tests (ACTH stimulation, dexamethasone suppression).

Specimen Types

  • Serum (total cortisol).
  • Plasma.
  • Saliva (late-night salivary cortisol).
  • 24-hour urine (urinary free cortisol).

Measurement Methods

  • Immunoassays (chemiluminescent, radioimmunoassay) for total cortisol.
  • Liquid chromatography–tandem mass spectrometry (LC‑MS/MS) for total or free cortisol.
  • Enzyme-linked immunoassays for salivary cortisol.

Test Preparation and Influencing Factors

  • Timing is critical: standard measurements usually at 8 a.m. (for suspected adrenal insufficiency) and late evening (for hypercortisolism).
  • Stress, acute illness, surgery, or hospitalization can transiently elevate levels.
  • Oral estrogens increase cortisol-binding globulin and total cortisol; certain drugs (e.g., anticonvulsants, rifampin) alter metabolism.
  • Sleep schedule, shift work, and pregnancy modify diurnal rhythm and reference ranges.
  • Recent glucocorticoid use (systemic, inhaled, topical) can suppress endogenous cortisol.

Synonyms

  • Hydrocortisone (pharmacologic name).
  • Serum cortisol.
  • Plasma cortisol.

Further Reading