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Total and free cortisol levels during 1 μg, 25 μg, and 250 μg cosyntropin stimulation tests compared to insulin tolerance test: results of a randomized, prospective, pilot study

  • Endocrine Methods and Techniques
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Abstract

Purpose

The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard.

Method

The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12). All tests were done in random order. Sensitivity and specificity were calculated for total cortisol and serum free cortisol cut-off levels during cosyntropin stimulation tests.

Results

The median (range) age and F/M sex ratios for patients and controls were 54 years (23–62), 2/8, and 33 years (21–51), 6/6, respectively. The best total cortisol cut-off during low dose cosyntropin test, medium dose cosyntropin test, 30 min and 60 min standard dose cosyntropin test were 14.6 μg/dL (100% sensitivity & specificity), 18.7 μg/dL (100% sensitivity, 88% specificity), 16.1 (100% sensitivity & specificity), and 19.5 μg/dL (100% sensitivity & specificity), respectively. There was no difference in the ROC curve for cortisol values between the cosyntropin stimulation tests (p  > 0.41). Using a cortisol cut-off of 18 μg/dL during cosyntropin stimulation tests, only cortisol level at 30 min during standard dose cosyntropin test provided discrimination similar to insulin tolerance test. The best peak free cortisol cut-off levels were 1 μg/dL for insulin tolerance test, 0.9 μg/dL for low dose cosyntropin test, 0.9 μg/dL for medium dose cosyntropin test, and 0.9 μg/dL and 1.3 μg/dL for 30 min and 60 min standard dose cosyntropin test, respectively.

Conclusion

All cosyntropin stimulation tests had excellent correlations with insulin tolerance test, when appropriate cut-offs were used. This pilot study does not suggest an advantage in using 25 μg cosyntropin dose during the cosyntropin stimulation test. A serum free cortisol cut-off of 0.9 μg/dL may be used as pass criterion during low dose cosyntropin test, standard dose cosyntropin test cosyntropin test, and 30 min standard dose cosyntropin test.

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Acknowledgements

We want to thank Linda Heil and Robert McCoy who served as research coordinators and the nursing staff at Clinical Research Unit at Cleveland Clinic for their help with performing the Insulin Tolerance Tests and Cosyntropin Stimulation Tests.

Funding

This study was partly funded by a grant from Endocrine Fellows Foundation awarded to Dr Seenia Peechakara and by the Research Program Committee at Cleveland Clinic Foundation awarded to Dr Amir Hamrahian. Quest Diagnostics Inc analyzed the samples for free.

Author information

Author notes

  1. Robert J. Weil

    Present address: National Clinical Enterprise, Catholic Health Initiatives, Englewood, CO, 80112, USA

Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA

    Seenia Peechakara, Laurence Kennedy & Amir H Hamrahian

  2. Quantitative Health Sciences, Lerner Research Institute, Cleveland, OH, 44195, USA

    James Bena

  3. Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, 92675, USA

    Nigel J. Clarke, Michael J. McPhaul & Richard E. Reitz

  4. Brain Tumor and Neuro-Oncology Center and Department of Neurosurgery, The Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA

    Robert J. Weil & Pablo Recinos

  5. Department of Endocrinology, Medical Subspecialty Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, PO Box 112412, Abu Dhabi, UAE

    Amir H Hamrahian

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  1. Seenia Peechakara
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Corresponding author

Correspondence to Seenia Peechakara.

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Conflict of interest

S.P., R.J.W., A.H.H., J.B., L.K., and P.R. report no conflicts of interests and have nothing to disclose. N.J.C., R.E.R., and M.J.M. are employees of Quest Diagnostics Inc and report no conflicts of interest. They were not involved in the trial design, data collection, and interpretation.

Ethical approval

All procedures performed in this study with human participants were in accordance with the ethical standards of the Cleveland Clinic institutional review board and with the 1964 Helsinki declaration and its later amendments. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Peechakara, S., Bena, J., Clarke, N.J. et al. Total and free cortisol levels during 1 μg, 25 μg, and 250 μg cosyntropin stimulation tests compared to insulin tolerance test: results of a randomized, prospective, pilot study. Endocrine 57, 388–393 (2017). https://doi.org/10.1007/s12020-017-1371-9

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