Advertisement

Endocrine

, Volume 55, Issue 1, pp 307–310 | Cite as

Dissociation of ACTH and cortisol in septic and non-septic ICU patients

  • Hershel RaffEmail author
  • Nebiyu Biru
  • Neil Reisinger
  • David J. Kramer
Research Letter

Introduction

The increase in circulating cortisol in septic intensive care unit (ICU) patients is not accompanied by increases in plasma adrenocorticotropic hormone (ACTH) [1]. This dissociation could be due to decreased metabolic clearance of cortisol and negative feedback inhibition of ACTH secretion [1]. The failure to maximally suppress ACTH secretion suggests an integration of activating central stress stimuli such as increased cytokines and inhibitory glucocorticoid negative feedback [2, 3, 4].

Another possible factor is the assay specificity for measuring plasma ACTH. Current human plasma ACTH assays use a two-site immunometric technology that is highly specific for human ACTH(1–39), and does not detect active or inactive pathophysiological concentrations of fragments or precursors of ACTH [5, 6]. It seems possible that other corticotrophic forms of ACTH might be increased during critical illness and detected by one-antibody competitive binding assays (e.g., radioimmunoassay...

Keywords

Hypothalamic-pituitary-adrenal axis Critical illness Adrenocorticotropin Cortisol 

Notes

Acknowledgments

ASLMC ICU supervisors, nurses, and staff; Anthony DeFranco MD, Richard Battiola MD, Catherine Warner, Ashley Gehrand, and Peter Homar. This study was funded in part by the Aurora Research Institute.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    E. Boonen, H. Vervenne, P. Meersseman, R. Andrew, L. Mortier, P.E. Declercq, Y.M. Vanwijngaerden, I. Spriet, P.J. Wouters, P.S. Vander, L. Langouche, I. Vanhorebeek, B.R. Walker, G. Van den Berghe, Reduced cortisol metabolism during critical illness. N. Engl. J. Med. 368(16), 1477–1488 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    H. Raff, J.W. Findling, A physiologic approach to diagnosis of the Cushing syndrome. Ann. Intern. Med. 138(12), 980–991 (2003)CrossRefPubMedGoogle Scholar
  3. 3.
    S. Melmed, Series introduction. The immuno-neuroendocrine interface. J. Clin. Invest. 108(11), 1563–1566 (2001). doi: 10.1172/JCI14604 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    N.R. Webster, H.F. Galley, Immunomodulation in the critically ill. Br. J. Anaesth. 103(1), 70–81 (2009). doi: 10.1093/bja/aep128 CrossRefPubMedGoogle Scholar
  5. 5.
    H. Raff, J.W. Findling, A new immunoradiometric assay for corticotropin evaluated in normal subjects and patients with Cushing’s syndrome. Clin. Chem. 35(4), 596–600 (1989)PubMedGoogle Scholar
  6. 6.
    C.W. Wilkinson, H. Raff, Comparative evaluation of a new immunoradiometric assay for corticotropin. Clin. Chem. Lab. Med. 44(5), 669–671 (2006). doi: 10.1515/CCLM.2006.113 CrossRefPubMedGoogle Scholar
  7. 7.
    W.A. Knaus, E.A. Draper, D.P. Wagner, J.E. Zimmerman, APACHE II: a severity of disease classification system. Crit. Care Med. 13(10), 818–829 (1985)CrossRefPubMedGoogle Scholar
  8. 8.
    J.I. Salluh, M. Soares, ICU severity of illness scores: APACHE, SAPS and MPM. Curr. Opin. Crit. Care 20(5), 557–565 (2014). doi: 10.1097/MCC.0000000000000135 CrossRefPubMedGoogle Scholar
  9. 9.
    R.P. Dellinger, M.M. Levy, A. Rhodes, D. Annane, H. Gerlach, S.M. Opal, J.E. Sevransky, C.L. Sprung, I.S. Douglas, R. Jaeschke, T.M. Osborn, M.E. Nunnally, S.R. Townsend, K. Reinhart, R.M. Kleinpell, D.C. Angus, C.S. Deutschman, F.R. Machado, G.D. Rubenfeld, S. Webb, R.J. Beale, J.L. Vincent, R. Moreno, Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 39(2), 165–228 (2013)CrossRefPubMedGoogle Scholar
  10. 10.
    M. Wade, S. Baid, K. Calis, H. Raff, N. Sinaii, L. Nieman, Technical details influence the diagnostic accuracy of the 1 microg ACTH stimulation test. Eur. J. Endocrinol. 162(1), 109–113 (2010). doi: 10.1530/EJE-09-0746 CrossRefPubMedGoogle Scholar
  11. 11.
    H. Raff, H. Trivedi, Circadian rhythm of salivary cortisol, plasma cortisol, and plasma ACTH in end-stage renal disease. Endocr. Connect. 2(1), 23–31 (2013). doi: 10.1530/EC-12-0058 CrossRefPubMedGoogle Scholar
  12. 12.
    H. Raff, P.J. Homar, D.P. Skoner, New enzyme immunoassay for salivary cortisol. Clin. Chem. 49(1), 203–204 (2003)CrossRefPubMedGoogle Scholar
  13. 13.
    B.M. Arafah, F.J. Nishiyama, H. Tlaygeh, R. Hejal, Measurement of salivary cortisol concentration in the assessment of adrenal function in critically ill subjects: a surrogate marker of the circulating free cortisol. J. Clin. Endocrinol. Metab. 92(8), 2965–2971 (2007). doi: 10.1210/jc.2007-0181 CrossRefPubMedGoogle Scholar
  14. 14.
    H. Raff, S. Brock, J.W. Findling, Cosyntropin-stimulated salivary cortisol in hospitalized patients with hypoproteinemia. Endocrine 34(1-3), 68–74 (2008)CrossRefPubMedGoogle Scholar
  15. 15.
    A.H. Hamrahian, T.S. Oseni, B.M. Arafah, Measurements of serum free cortisol in critically ill patients. N. Engl. J. Med. 350(16), 1629–1638 (2004)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Endocrine Research Laboratory, Aurora St. Luke’s Medical CenterAurora Research InstituteMilwaukeeUSA
  2. 2.Department of Medicine, Surgery, and PhysiologyMedical College of WisconsinMilwaukeeUSA
  3. 3.Internal MedicineAurora St. Luke’s Medical CenterMilwaukeeUSA
  4. 4.Aurora Critical Care ServiceAurora St. Luke’s Medical CenterMilwaukeeUSA
  5. 5.Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA

Personalised recommendations