Cortisol, Serum


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Subject: Cortisol, Serum

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  • Cortisol (hydrocortisone) is the major glucocorticoid produced and secreted by the adrenal cortex. It affects the metabolism of protein, fat, and carbohydrates; maintenance of muscle and myocardial integrity; and the suppression of inflammatory and allergic activities.

  • Normal range:

    • am cortisol: 8.7–22.4 μg/dL

    • pm cortisol: <10 μg/dL


  • Discrimination between primary and secondary adrenal insufficiency

  • Differential diagnosis of Cushing syndrome


  • The most common cause of increased plasma cortisol levels in women is a high circulating concentration of estrogen (e.g., estrogen therapy, pregnancy), resulting in increased concentration of cortisol-binding globulin.

  • Patients with severe illness and sepsis have reduced cortisol-binding globulin and albumin levels, resulting in lowered cortisol levels.


  • Bound cortisol circulates in an available but temporarily inactive state. The physiologic activity of cortisol depends on levels of the small fraction of circulating unbound cortisol.

  • Acute stress (including hospitalization and surgery), alcoholism, depression, and many drugs (e.g., exogenous cortisones, anticonvulsants) can obliterate normal diurnal variation, affect response to suppression/stimulation tests, and cause elevated baseline levels.

  • Patients taking prednisone may have falsely increased cortisol levels because prednisone is converted to prednisolone after ingestion, and prednisolone has a 41% cross-reactivity.

  • Cortisol levels may be increased in pregnancy and with exogenous estrogens.

  • Some patients with depressive disorders have a hyperactive hypothalamic–pituitary–adrenal axis, similar to Cushing syndrome.