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Cortisol Test

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About Our Cortisol Test

Cortisol, the main adrenal glucocorticoid, is produced and secreted by the adrenal glands in response to pituitary adrenocorticotropic hormone (ACTH), which itself is regulated by hypothalamic corticotropin-releasing hormone (CRH) via a classic negative-feedback loop. Cortisol circulates bound to cortisol-binding globulin (CBG) and albumin, with less than 5% circulating in a free, unbound state. Free cortisol is the physiologically active form and has a half-life of 80 to 100 minutes. Cortisol functions to maintain homeostasis, regulate metabolism, and participates in the immune inflammatory response. 

Serum cortisol levels are used primarily to diagnose hypercortisolism (Cushing syndrome) or hypocortisolism (Addison disease). Serum cortisol levels fluctuate rapidly in response to a variety of stimuli (eg, sepsis, time of day, exogenous glucocorticoid use, surgical procedures) making interpretation of a single value difficult. Provocative testing is required to accurately evaluate cortisol excess or insufficiency.


Decreased levels of cortisol:

  • Hypothalamic insufficiency
  • Pituitary insufficiency
  • Adrenal dysfunction (ie, Addison disease)
  • Hypothyroidism
  • Corticosteroid long-term use (suppresses endogenous cortisol production)
  • Certain medications (eg, androgens, phenytoin)
  • Sepsis (by decreasing cortisol binding globulin concentration)

Increased levels of cortisol:

  • Excess pituitary production of ACTH due to a pituitary adenoma (ie, Cushing Disease, most common)
  • Adrenal gland overproduction (eg, solitary adrenal adenoma, nodular hyperplasia, rarely adrenal carcinoma)
  • Ectopic ACTH-secreting tumor (eg, pancreas, lung, thyroid, thymus)
  • Concurrent trauma, surgery, sepsis
  • Depression
  • Alcoholism
  • Obesity
  • Pregnancy or hormone therapy (due to increased cortisol binding globulin)
  • Recent hydrocortisone (cortisol) or cortisone use

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