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Free Cortisol Is a More Accurate Marker for Adrenal Function and Does Not Correlate with Renal Function in Cirrhosis

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Abstract

Background

The accuracy of diagnosis and clinical implications of the hepatoadrenal syndrome, as currently diagnosed using total cortisol, remain to be validated.

Aim

The aim of this study was to assess adrenal function using free cortisol in stable cirrhosis and study the potential implications of any abnormalities for renal and/or cardiac function.

Methods

Sixty-one stable consecutively enrolled patients with cirrhosis underwent assessment of adrenal function using the low-dose short Synacthen test, renal function by 51Cr-EDTA glomerular filtration rate (GFR), and cardiac function by two-dimensional echocardiography.

Results

Eleven patients (18%) had total peak cortisol (PC) < 500 nmol/L, but no patient had free PC < 33 nmol/L indicating that diagnosis of AI using total cortisol is not confirmed using free cortisol. Free cortisol did not correlate with GFR or parameters of cardiac function. Patients with higher Child–Pugh class had progressively lower free cortisol. Patients with low GFR < 60 mL/min (N = 22) had more frequently grade II–III diastolic dysfunction (66.7% vs. 17.6%; p = 0.005) and had higher Child–Pugh and MELD score compared to those with normal GFR.

Conclusions

Diagnosis of AI using total cortisol is not confirmed using free cortisol and is thus considered unreliable in cirrhosis. Free cortisol is not associated with renal or cardiac dysfunction. Lower free cortisol in more advanced stages of liver disease might be secondary to decreased synthesis due to lower cholesterol levels. Irrespective of free cortisol, parameters of cardiac dysfunction are associated with renal impairment supporting the cardio–renal hypothesis.

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References

  1. Fede G, Spadaro L, Tomaselli T, et al. Adrenocortical dysfunction in liver disease: a systematic review. Hepatology (Baltimore, Md.). 2015;55:1282–1291.

    Article  CAS  Google Scholar 

  2. Arlt W, Allolio B. Adrenal insufficiency. Lancet (London, England). 2003;361:1881–1893.

    Article  CAS  Google Scholar 

  3. Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008;36:1937–1949.

    Article  CAS  PubMed  Google Scholar 

  4. Fede G, Spadaro L, Tomaselli T, et al. Assessment of adrenocortical reserve in stable patients with cirrhosis. J Hepatol. 2011;54:243–250.

    Article  PubMed  Google Scholar 

  5. Trifan A, Chiriac S, Stanciu C. Update on adrenal insufficiency in patients with liver cirrhosis. World J Gastroenterol. 2013;19:445–456.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Thevenot T, Borot S, Remy-Martin A, et al. Assessing adrenal function in cirrhotic patients: Is there a reliable test? Gastroenterol Clin Biol. 2009;33:584–588.

    Article  CAS  PubMed  Google Scholar 

  7. Fernandez J, Escorsell A, Zabalza M, et al. Adrenal insufficiency in patients with cirrhosis and septic shock: effect of treatment with hydrocortisone on survival. Hepatology (Baltimore, Md.). 2006;44:1288–1295.

    Article  CAS  Google Scholar 

  8. Acevedo J, Fernandez J, Prado V, et al. Relative adrenal insufficiency in decompensated cirrhosis: Relationship to short-term risk of severe sepsis, hepatorenal syndrome, and death. Hepatology (Baltimore, Md.). 2013;58:1757–1765.

    Article  CAS  Google Scholar 

  9. Theocharidou E, Krag A, Bendtsen F, Moller S, Burroughs AK. Cardiac dysfunction in cirrhosis: does adrenal function play a role? A hypothesis. Liver Int. 2012;32:1327–1332.

    Article  PubMed  Google Scholar 

  10. Alqahtani SA, Fouad TR, Lee SS. Cirrhotic cardiomyopathy. Semin Liver Dis. 2008;28:59–69.

    Article  CAS  PubMed  Google Scholar 

  11. Zambruni A, Trevisani F, Di Micoli A, et al. Effect of chronic beta-blockade on QT interval in patients with liver cirrhosis. J Hepatol. 2008;48:415–421.

    Article  PubMed  Google Scholar 

  12. Tan T, Chang L, Woodward A, et al. Characterising adrenal function using directly measured plasma free cortisol in stable severe liver disease. J Hepatol. 2010;53:841–848.

    Article  CAS  PubMed  Google Scholar 

  13. Vincent RP, Etogo-Asse FE, Dew T, Bernal W, Alaghband-Zadeh J, le Roux CW. Serum total cortisol and free cortisol index give different information regarding the hypothalamus-pituitary-adrenal axis reserve in patients with liver impairment. Ann Clin Biochem. 2009;46:505–507.

    Article  CAS  PubMed  Google Scholar 

  14. Davenport A, Cholongitas E, Xirouchakis E, Burroughs AK. Pitfalls in assessing renal function in patients with cirrhosis–potential inequity for access to treatment of hepatorenal failure and liver transplantation. Nephrol Dial Transpl. 2011;26:2735–2742.

    Article  Google Scholar 

  15. Cholongitas E, Shusang V, Marelli L, et al. Review article: renal function assessment in cirrhosis: difficulties and alternative measurements. Aliment Pharm Ther. 2007;26:969–978.

    Article  CAS  Google Scholar 

  16. Sterner G, Frennby B, Mansson S, Nyman U, Van Westen D, Almen T. Determining ‘true’ glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations. Scand J Urol Nephrol. 2008;42:278–285.

    Article  CAS  PubMed  Google Scholar 

  17. Galbois A, Rudler M, Massard J, et al. Assessment of adrenal function in cirrhotic patients: salivary cortisol should be preferred. J Hepatol. 2010;52:839–845.

    Article  CAS  PubMed  Google Scholar 

  18. Davenport A. Difficulties in assessing renal function in patients with cirrhosis: potential impact on patient treatment. Intensive Care Med. 2011;37:930–932.

    Article  PubMed  Google Scholar 

  19. O’Beirne J, Holmes M, Agarwal B, et al. Adrenal insufficiency in liver disease: What is the evidence? J Hepatol. 2007;47:418–423.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

Professor Andrew K. Burroughs contributed to the conception of this study prior to his premature death.

Funding

The studied was funded by the Hellenic Society for the Study of the Liver.

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Correspondence to Christos S. Mantzoros.

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Theocharidou, E., Giouleme, O., Anastasiadis, S. et al. Free Cortisol Is a More Accurate Marker for Adrenal Function and Does Not Correlate with Renal Function in Cirrhosis. Dig Dis Sci 64, 1686–1694 (2019). https://doi.org/10.1007/s10620-019-5460-x

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