Cortisol

Cortisol is the principal glucocorticoid stress hormone produced by the adrenal cortex, regulating glucose metabolism, immune function, and the body's response to physiological and psychological stress.

Cortisol is a glucocorticoid hormone synthesised in the adrenal cortex under stimulation from pituitary adrenocorticotropic hormone (ACTH). It governs glucose mobilisation, immune modulation, blood pressure regulation, and the body's adaptive response to stress. Cortisol follows a strong diurnal rhythm — highest within 30 minutes of waking, lowest around midnight.

Regulation

The hypothalamic-pituitary-adrenal (HPA) axis controls cortisol release. The hypothalamus secretes corticotropin-releasing hormone (CRH), which stimulates pituitary ACTH release, which in turn drives adrenal cortisol synthesis.

Cortisol feeds back negatively on both the hypothalamus and pituitary, completing the loop. Chronic stress can dysregulate this feedback, producing flattened diurnal rhythms or persistently elevated baseline cortisol.

Clinical measurement

Morning (8am) serum cortisol is the standard first-line screen. Reference range typically 138-690 nmol/L. Below this range suggests adrenal insufficiency (Addison's); above suggests Cushing's syndrome or acute stress response.

Diurnal cortisol assessment (4-point salivary or serial serum) is used when the rhythm itself is in question — e.g. suspected chronic stress dysregulation or atypical Cushing's presentations.

Clinical significance

Hypercortisolism: Cushing's syndrome (rare, requires investigation), exogenous corticosteroid use, severe chronic stress, sleep deprivation.

Hypocortisolism: primary adrenal insufficiency (Addison's disease), pituitary failure, long-term suppression from exogenous steroids.

Chronic mild elevation is implicated in insulin resistance, visceral fat accumulation, suppression of the HPG axis (and therefore testosterone), and impaired immune function.

References

Related concepts

Testosterone — Testosterone is the primary male sex hormone, an androgen produced mainly in the testes that regulates libido, muscle mass, bone density, red blood cell production, and mood.
Sex Hormone-Binding Globulin (SHBG) — SHBG is a liver-produced glycoprotein that binds sex hormones (primarily testosterone and oestradiol) in the bloodstream, regulating their bioavailability.