What is the role of random plasma cortisol testing in the workup of Addison disease?

Updated: Mar 11, 2020
  • Author: George T Griffing, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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In acute adrenal crisis, where treatment should not be delayed in order to do the tests, a blood sample for a random plasma cortisol level should be drawn prior to starting hydrocortisone replacement.

  • A random plasma cortisol value of 25 mcg/dL or greater effectively excludes adrenal insufficiency of any kind. However, a random cortisol value in patients who are acutely ill should be interpreted with caution and in correlation with the circumstances of each individual patient. Random cortisol levels should also be interpreted cautiously in critically ill patients with hypoproteinemia (serum albumin < 2.5 g/dL). Approximately 40% of these patients will have baseline and cosyntropin-stimulated cortisol levels below the reference range even though the patients have normal adrenal function (as evidenced by the measurement of free cortisol levels). This phenomenon is because more than 90% of circulating cortisol in human serum is protein bound.

  • Cortisol is known to be elevated by stress, but exactly how high it should rise to constitute a normal response in times of severe stress is not known.

  • An abnormal test result should prompt a proper evaluation of the hypothalamic pituitary adrenal axis after the patient's condition improves before committing a patient to lifelong steroid replacement.

  • In order to perform the ACTH stimulation test in this situation, the patient should be switched to dexamethasone and then tested 24-36 hours later. Dexamethasone does not interfere with the cortisol assay, as does hydrocortisone or prednisone. However, dexamethasone may interfere with interpretation of the random cortisol value drawn after dexamethasone already has been initiated. Dexamethasone also does not have any mineralocorticoid activity, which may be needed in patients with Addison disease.

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