Interpretation

Cortisol is converted to cortisone in human kidneys and cortisone is less active toward the mineralocorticoid receptor. The conversion of cortisol to cortisone in the kidney is mediated by 11- beta-hydroxysteroid dehydrogenase isoform-2. Also, cortisol renal clearance will be reduced when there is a deficiency in the cytochrome P450 3A5 (CYP3A5) enzyme as well as a deficiency in P-glycoprotein.

Cortisol-binding globulin (CBG) has a low capacity and high affinity for cortisol, whereas albumin has a high capacity and low affinity for binding cortisol. Variations in CBG and serum albumin due to kidney or liver disease may have a major impact on free cortisol.

Based on the study by Bancos,(1) normal ranges of free cortisol found in patients without adrenal insufficiency were:

-Free cortisol at baseline: median 0.400 mcg/dL (interquartile range: IQR 2.5%-97.5%: 0.110-1.425 mcg/dL)

-Free cortisol at 30 minutes: median 1.355 mcg/dL (IQR 2.5%-97.5%: 0.885-2.440 mcg/dL)

-Free cortisol at 60 minutes: median 1.720 mcg/dL (IQR 2.5%-97.5%: 1.230-2.930 mcg/dL)

Based on the study by Bancos,(1) the following cutoffs were calculated for exclusion of adrenal insufficiency:

-Free cortisol at baseline*: greater than 0.271 mcg/dL (>271 ng/dL, area under the curve: AUC 0.81)

-Free cortisol at 30 minutes: greater than 0.873 mcg/dL (>873 ng/dL, AUC 0.99)

-Free cortisol at 60 minutes: greater than 1.190 mcg/dL (>1190 ng/dL, AUC 0.99)

(*note that baseline free cortisol should not be used to exclude adrenal insufficiency given low performance)

The use of free cortisol in the management of glucocorticoid levels in the stressed patient due to major surgery or trauma requires further studies to establish clinical dosing levels and efficacy.

Cortisol pediatric reference ranges are generally the same as adults as confirmed by peer-reviewed literature.(2)

In primary adrenal insufficiency, corticotropin (previously adrenocorticotropic hormone: ACTH) levels are increased and cortisol levels are decreased; in secondary adrenal insufficiency both ACTH and cortisol levels are decreased.

When symptoms of glucocorticoid deficiency are present and the 8 a.m. plasma cortisol value is less than 10 mcg/dL (or the 24-hour urinary free cortisol value is <50 mcg/24 hours), additional studies are needed to establish the diagnosis. The 3 most frequently used tests are the ACTH (cosyntropin) stimulation test, the metyrapone test, and insulin-induced hypoglycemia test. First, the basal plasma ACTH concentration should be measured and the short cosyntropin stimulation test performed.

Symptoms or signs of Cushing syndrome in a patient with low serum and urine cortisol levels suggest possible exogenous synthetic steroid effects.