Cortisol

Cortisol is the primary glucocorticoid of the adrenal cortex. In the circulation, 80 to 90% of cortisol is bound to corticosteroid binding globulin (CBG) and 7% to albumin. The remaining 3% is unbound. Clinical laboratory measurement of cortisol includes all three forms.

Cortisol secretion has a pronounced diurnal variation. Concentrations are highest in the morning, around 08:00, and lowest at midnight. Random measurements of plasma cortisol are of little value in evaluating the patient with suspected adrenal cortical insufficiency because of the diurnal variation and the effects of stress. Obese patients tend to have increased cortisol production.

In patients with Cushing's syndrome, cortisol secretion is increased and the normal circadian rhythm is absent. If the 16:00 cortisol level is greater than 75% of the 08:00 level, cortisol secretion is considered to be abnormal. This criterion has a sensitivity and specificity for Cushing's syndrome of 70% and 82% respectively. If a cut off point for the 16:00 cortisol level of greater than 50% of the 08:00 level is used, then all patients with Cushing's syndrome will lack diurnal variation. However, approximately one third of obese patients will also not exhibit diurnal variation. 

During severe illness, many factors can impair the normal corticosteroid response. These factors include pituitary apoplexy, CNS disease, inflammatory cytokines, anti-infective drugs, hemorrhage, exogenous corticosteroids and HIV infection. Recognizing the clinical manifestations of adrenal insufficiency in a critically ill patient is extremely difficult. With the increasing use of steroid replacement therapy for critically ill patients, an important issue is the cross-reactivity of steroid medications with the cortisol assay performed. The following table summarizes the degree of cross-reactivity with cortisol measured on a Siemens Centaur analyzer. This type of study is accomplished by comparing cortisol levels in a serum that has been spiked with a particular steroid with the same sample that has not been spiked.

As demonstrated in the table, treatment of patients with dexamethasone, fludrocortisone or hydrocortisone does not significantly affect cortisol measurements. 

Cortisol reference ranges for adults vary by the time of day.

Specimen requirement is one SST tube containing a minimum of 2 mL of blood.

References

Loriaux DL, Diagnosis and Differential Diagnosis of Cushing’s Syndrome, New Engl J Med.2017;376:1451-1459.

Reincke M, Fleseriu M. Cushing Syndrome: A Review, JAMA 2023;330:170-181.