Cortrosyn-stimulated Serum Free Cortisol in Healthy, Adrenally Insufficient, and Cirrhotic Populations

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 1-16-Adrenal Insufficiency
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-1
Mitra Lynn Rauschecker, Smita Baid Abraham, Brent Samuel Abel, Elizabeth Saverino, Robert Wesley and Lynnette Kaye Nieman*
NIH, Bethesda, MD
Background: Concentrations of serum proteins, including cortisol-binding globulin (CBG), may be decreased in abnormal protein states such as cirrhosis, so that total cortisol (TF) levels may not accurately reflect adrenal function. Serum free cortisol (SFF) is less affected by protein status and may provide a more accurate assessment of adrenal function. There are few normative data for SFF levels in any population. We evaluated the diagnostic utility of SFF during a 250 μg Cortrosyn stimulation test in healthy volunteers (HV) and patients (pts) with primary adrenal insufficiency (PAI), secondary adrenal insufficiency (SAI), and cirrhosis (CH).

Methods:  Adrenal insufficiency was highly suspected or documented previously in PAI and SAI pts and was confirmed in the current study. CH pts had known viral cirrhosis, Child-Pugh class A or B.  HV had stable chronic conditions (n=4) or no known medical problems. TF (competitive chemiluminescent enzyme immunoassay) and SFF (LC-MS/MS after equilibrium dialysis) were obtained at baseline (BL), 30, and 60 min after administration of 250 μg Cortrosyn intravenously. Plasma ACTH and CBG levels were measured at BL. Data are shown as mean + SD (range).

Results: We studied 28 HV (47±12.9y, 13 women [W]) and 49 pts (PAI, n=19, 47±17.7y, 12 W; SAI, n=24, 44±13.5y, 17 W; CH, n=6, 59±6.0y, 2 W).  All HV and CH pts had peak TF values >18 μg/dL; all PAI and most SAI pts had values < 18 μg/dL; one SAI pt had TF=20.6 μg/dL. Mean BL SFF in HV, CH, PAI, and SAI were: 0.38±0.40 (0.07-1.86), 0.43±0.15 (0.21-0.65), 0.06±0.03 (0.03-0.14), and 0.09±0.09 (0.03-0.36) µg/dL, respectively. Peak SFF in HV, CH, PAI and SAI were: 1.97±0.55 (0.91-2.89), 2.6±0.42 (1.99-2.93), 0.07±0.06 (0.03-0.26), and 0.27±0.33 (0.03-1.27) µg/dL, respectively.  Mean CBG levels in CH (3.0±0.41 mg/L) did not differ from those of the other groups. CH pts had significantly higher peak SFF than HV (2.6 vs. 1.9 μg/dL; P=0.01). When compared with PAI pts, SAI pts had significantly higher peak SFF and TF (0.27, 6.81 μg/dL vs. 0.07, 2.23 μg/dL; P<0.01 for both). The optimal peak SFF criterion to distinguish HV vs. AI pts was 0.9 μg/dL (sens=100%, spec=95%).

Conclusion: We provide a normative data range for Cortrosyn-stimulated SFF values in HV and pts with AI.  While limited by small numbers, pts with Child Pugh Class A or B cirrhosis did not appear to have total protein abnormalities, as assessed by CBG, that affected interpretation of the Cortrosyn stimulation test. 

1. Hamrahian AH, Oseni TS, Arafah BM.  Measurements of serum free cortisol in critically ill pts. N Engl J Med. 2004, 350:1629-38.

Nothing to Disclose: MLR, SBA, BSA, ES, RW, LKN

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Sources of Research Support: This work was supported in part by the intramural program of NICHD, NIH. 
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