What is the difference between blood, urine and saliva cortisol testing?

*This information is to be used for educational purposes only and is not intended to provide medical care or advice*

There are three forms of cortisol in the body:

1.Free cortisol

2.Bound cortisol

3.Cortisol metabolites

Bound Cortisol– Cortisol which is attached to a specific protein (CBG) is known as a bound cortisol. Metabolized cortisol evaluates how much cortisol is being made in total and cleared through the liver.

Free Cortisol- Cortisol which is not attached to any protein known as free cortisol. Free cortisol reveals how much cortisol is free to bind to receptors and allows for assessment of the circadian rhythm.

Cortisol metabolites– Metabolites of cortisol gives insight into the relative activity of 11b-HSD types I and II, which controls the activation and inactivation (to cortisone) of cortisol.

Approximately 90% of cortisol is bound to cortisol-binding globulin (CBG), also known as transcortin, and albumin.  Transcortin: corticosteroid-binding globulin (CBG) or serpin A6, is a protein encoded by the SERPINA6 gene and is an alpha-globulin. Albumin: main protein in your blood and carries substances such as hormones, vitamins, and enzymes throughout the body.

5% of circulating cortisol is free (unbound). Only free cortisol can access the enzyme transporters in the liver, kidney, and other tissues that mediate metabolic and excretory clearance.

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 renal or liver disease may have a major impact on free cortisol.

Standard Ranges for Cortisol:

A normal adult range for cortisol levels in urine is between 3.5 and 45 micrograms per 24 hours.

Reference ranges for salivary cortisol assay: <0.4–3.6 nmol/L at 2300 h & 4.7–32.0 nmol/L at 0700 h.

Standard 8 a.m. range for blood serum cortisol is between 6 and 23 micrograms per deciliter (mcg/dL)

Measuring both free and bound cortisol levels allows for insight into the rate of cortisol clearance/metabolism and clearance.

Urine and saliva cortisol testing are used to evaluate free cortisol levels. Morning saliva cortisol panels are done to measure the diurnal cortisol curve. Blood cortisol testing is used to evaluate total cortisol and also bound cortisol.

In patients with adrenal insufficiency, an evaluation of cortisol tested via blood, saliva and urine can all be beneficial in evaluating the efficacy of their cortisol replacement medication(s). Recommended protocols are a comparative assay of cortisol levels from urine, blood and saliva specimens. The patient’s quality of life, symptomatic complaints and also fatigue levels should also be used when evaluating a proper cortisol dosing regimen.

Sources:

Abraham, S. B., Rubino, D., Sinaii, N., Ramsey, S., & Nieman, L. K. (2013). Cortisol, obesity and the metabolic syndrome: A cross-sectional study of obese subjects and review of the literature. Obesity (Silver Spring), 21(1), 1-24. doi:10.1002/oby.20083

Dhillo WS, Kong WM, Le Roux CW, Alaghband-Zadeh J, Jones J, Carter G, Mendoza N, Meeran K and O’Shea D. Cortisol-binding globulin is important in the interpretation of dynamic tests of the hypothalamic-pituitary-adrenal axis. Euro J Endo. 2002;146

Hoshiro, M., Ohno, Y., Masaki, H., Iwase, H., & Aoki, N. (2006). Comprehensive Study of Urinary Cortisol Metabolites in Hyperthyroid and Hypothyroid Patients. Clinical Endocrinology, 64, 37-45. doi:10.1111/j.1365-2265.2005.02412.x

Taniyama, M., Honma, K., & Ban, Y. (1993). Urinary Cortisol Metabolites in the Assessment of peripheral Thyroid Hormone Action for Diagnosis of Resistance to Thyroid Hormone. Thyroid, 3, 229-233.

Tomlinson, J. W., Finney, J., Hughes, B. A., Hughes, S. V., & Stewart, P. M. (June 2008). Reducing Glucocorticoid Production Rate, Decreased 5alpha-Reductase Activity, and Adipose Tissue Insulin Sensitization After Weight Loss. Diabetes, 57, 1536-1543.

Bancos I, Erickson D, Bryant S, et al: Performance of free versus total cortisol following cosyntropin stimulation testing in an outpatient setting. Endocr Pract 2015 Dec;21(12):1353-1363 doi: 10.4158/EP15820

Petersen KE: ACTH in normal children and children with pituitary and adrenal diseases. I. Measurement in plasma by radioimmunoassay-basal values. Acta Paediatr Scand 1981;70:341-345

Hamrahian AH, Oseni TS, Arafah BM: Measurements of serum free cortisol in critically ill patients. N Engl J Med 2004;350;16:1629-1638

Ho JT, Al-Musalhi H, Chapman MJ, et al: Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab 2006;91:105-114

le Roux CW, Chapman GA, Kong WM, et al: Free cortisol index is better than serum total cortisol in determining hypothalamic-pituitary-adrenal status in patients undergoing surgery. J Clin Endocrinol Metab 2003;88:2045-2048

Huang W, Kalhorn TF, Baillie M, et al: Determination of free and total cortisol in plasma and urine by liquid chromatography-tandem mass spectrometry. Ther Drug Monit 2007;29(2):215-224

Mayo Clinic Laboratories-  https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/65484

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