Cortisol, Free, Equilibrium Dialysis and LC/MS-MS

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Turnaround Time: 6 - 10 days
CPT Code:


Test Type: 1.6 mL Serum, frozen
Stability Time:

Freeze. Stable at room temperature or refrigerated for seven days. Stable frozen for six months. Freeze/thaw cycles stable x6.


Cortisol is the primary glucocorticoid in humans, affecting glucose control, inflammation, and response to stress.

Results of this test are for investigational purposes only. The performance characteristics of this assay have been determined by LabCorp. The result should not be used as a diagnostic procedure without confirmation of the diagnosis by another medically established diagnostic product or procedure.

Cortisol stimulates gluconeogenesis in the liver and reduces insulin secretion while increasing glucagon release by the pancreas. This increases blood glucose levels. Cortisol is also involved in inhibiting inflammatory responses and maintaining blood pressure by potentiating effects on norepinephrine.

Most of circulating cortisol is bound to protein, primarily transcortin (corticosteroid-binding globulin [CBG]) and albumin. The free hormone hypothesis suggests that the unbound, or free, cortisol is the active fraction, and that this fraction is the most important clinically. Total serum cortisol may be an adequate measure of cortisol activity except when the levels of the binding proteins are abnormal such as in liver disease or acute illness.

A study published in the New England Journal of Medicine demonstrates the utility of measurements of free cortisol in critically ill patients. Patients with critical illness increase cortisol secretion; however, this is best observed when free cortisol levels are measured. In the study, 40% of patients with hypoproteinemia had low levels of total cortisol even though their adrenal function was adequate as demonstrated by robust response to ACTH. Similar results were obtained when salivary cortisol was used as a marker for adrenal sufficiency during illness.

A number of tests to determine free cortisol have been devised. The free fraction depends on the concentrations of the binding proteins and cortisol, and, thus, may be calculated based on these factors. Free cortisol is best measured by equilibrium dialysis. Structure-function observations favor a direct measure of free cortisol. There are polymorphic forms of transcortin that affect cortisol binding, and glycosylation affects cortisol binding to transcortin. The Cortisol, Free, Equilibrium Dialysis and LC/MS-MS assay provides a specific direct test.

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Lin HY, Underhill C, Lei JH, Helander-Claesson A, Lee HY, Gardill BR, Muller YA, Wang H, Hammond GL. High frequency of SERPINA6 polymorphisms that reduce plasma corticosteroid-binding globulin activity in Chinese subjects. J Clin Endocrinol Metab. 2012 Apr; 97(4): E678-686. PubMed 22337907

Collection Details:

Collection Instructions:

Red-top tube or gel-barrier tube.

Separate within two hours of venipuncture. Transfer specimen to a plastic transport tube before freezing.

Freeze. Stable at room temperature or refrigerated for seven days. Stable frozen for six months. Freeze/thaw cycles stable x6.