FREE CORTISOL MEASUREMENT BY EQUILIBRIUM DIALYSIS FOLLOWED BY LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 26-40-Glucocorticoid Actions & Disease
Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-27
Irina Bancos*1, Ravinder Jit Singh1, Sandra c Bryant2, Kristi Mielke2, Jolaine Hines2, Neena Natt1, Todd B Nippoldt1 and Dana Z Erickson1
1Mayo Clinic, Rochester, MN, 2Mayo Clinic
Context: While 10% of total cortisol is free and considered biologically active, measurements of total cortisol levels after cosyntropin stimulation are used in current clinical practice in evaluation of adrenal insufficiency. Total cortisol comprises cortisol bound to proteins (such as CBG and albumin) and free cortisol. As there is a high inter- and intraindividual variability of binding proteins influenced by disease states or medications, measurement of free cortisol fraction can potentially improve diagnosis of adrenal insufficiency, especially in the borderline cases.

Aim: Our aim was to investigate the relationship between free cortisol and total cortisol levels in subjects undergoing 250 mcg Cosyntropin stimulation test for suspected or established adrenal insufficiency.

Methods: After signing the consent form, 296 consecutive subjects undergoing Cosyntropin stimulation testing at the outpatient Endocrine testing center underwent total and free cortisol measurements at baseline, 30 and 60 minutes.  Free cortisol levels were measured by equilibrium dialysis followed by liquid chromatography tandem mass spectrometry, an in-house developed assay. Adrenal insufficiency was defined as failure to reach a level of 18 mg/dl for total cortisol. ROC (receiver-operator characteristic) analysis was used to identify the most optimal cut-point of free cortisol values to distinguish between the group with confirmed adrenal insufficiency and the group without adrenal insufficiency.

Results: Of the 296 patients participating in this study (mean age of 48.8 ± 17.1, 77 males (26%)), 42 subjects (14%) were classified as adrenally insufficient. Causes of adrenal insufficiency included: steroid use (52%), Addison’s (12%),  adrenalectomy for a cortisol producing adenoma (7%), medications or sleep apnea (5%), idiopathic secondary ACTH deficiency (2%), pituitary lesion (4%), Cushing’s disease with pituitary adenoma resection (2%), Sheehan syndrome (2%), unknown (12%). ROC curves for free cortisol were derived with a 60 minute cutpoint at 1190 ng/dl (CI 95% 1030-1210) providing the best AUC of 0.99 (CI 95% 0.98-0.99), p<0.0001. Patients on oral estrogens (n=43, 15%) had higher baseline total cortisol levels but no difference in baseline free cortisol concentrations when compared to non-estrogen group. Both 30 min. and 60 min. free and total stimulated cortisol levels were similar across estrogen and non-estrogen groups. In the group receiving oral estrogen and classified as adrenally sufficient,  4 of 37 patients (10.8%)  would have been defined as  adrenally insufficient using the 60 min. free cortisol cut-off defined by only those patients not using estrogen replacement (1170 ng/dl) .

Conclusion: Free cortisol measurement is a potential useful tool for determination of adrenal insufficiency, especially in borderline cases.

Disclosure: DZE: Advisory Group Member, Ipsen. Nothing to Disclose: IB, RJS, SCB, KM, JH, NN, TBN

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm