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

  • Eleni Theocharidou
  • Olga Giouleme
  • Sotirios Anastasiadis
  • Aikaterini Markopoulou
  • Efstathios Pagourelias
  • Themistoklis Vassiliadis
  • Athanasios Fotoglidis
  • Polyxeni Agorastou
  • Aristeidis Slavakis
  • Aikaterini Balaska
  • Maria G. Kouskoura
  • Thomas D. Gossios
  • Asterios Karagiannis
  • Christos S. MantzorosEmail author
Original Article
  • 26 Downloads

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.

Keywords

Adrenal insufficiency Cirrhotic cardiomyopathy Hepatoadrenal syndrome Hepatorenal syndrome 

Notes

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.

Compliance with ethical standards

Conflict of interest

No conflicts of interest.

Supplementary material

10620_2019_5460_MOESM1_ESM.docx (26 kb)
Supplementary material 1 (DOCX 25 kb)

References

  1. 1.
    Fede G, Spadaro L, Tomaselli T, et al. Adrenocortical dysfunction in liver disease: a systematic review. Hepatology (Baltimore, Md.). 2015;55:1282–1291.CrossRefGoogle Scholar
  2. 2.
    Arlt W, Allolio B. Adrenal insufficiency. Lancet (London, England). 2003;361:1881–1893.CrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. 4.
    Fede G, Spadaro L, Tomaselli T, et al. Assessment of adrenocortical reserve in stable patients with cirrhosis. J Hepatol. 2011;54:243–250.PubMedCrossRefGoogle Scholar
  5. 5.
    Trifan A, Chiriac S, Stanciu C. Update on adrenal insufficiency in patients with liver cirrhosis. World J Gastroenterol. 2013;19:445–456.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 10.
    Alqahtani SA, Fouad TR, Lee SS. Cirrhotic cardiomyopathy. Semin Liver Dis. 2008;28:59–69.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 18.
    Davenport A. Difficulties in assessing renal function in patients with cirrhosis: potential impact on patient treatment. Intensive Care Med. 2011;37:930–932.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Eleni Theocharidou
    • 1
  • Olga Giouleme
    • 2
  • Sotirios Anastasiadis
    • 2
  • Aikaterini Markopoulou
    • 3
  • Efstathios Pagourelias
    • 4
  • Themistoklis Vassiliadis
    • 5
  • Athanasios Fotoglidis
    • 4
  • Polyxeni Agorastou
    • 2
  • Aristeidis Slavakis
    • 6
  • Aikaterini Balaska
    • 7
  • Maria G. Kouskoura
    • 3
  • Thomas D. Gossios
    • 2
  • Asterios Karagiannis
    • 2
  • Christos S. Mantzoros
    • 8
    Email author
  1. 1.Institute of Liver StudiesKing’s College HospitalLondonUK
  2. 2.2nd Propaedeutic Department of Internal Medicine, Hippokration General HospitalAristotle University of ThessalonikiThessaloníkiGreece
  3. 3.School of Pharmacy, Laboratory of Pharmaceutical AnalysisAristotle University of ThessalonikiThessaloníkiGreece
  4. 4.3rd Department of Cardiology, Hippokration General HospitalAristotle University of ThessalonikiThessaloníkiGreece
  5. 5.3rd Department of Internal Medicine, Papageorgiou General HospitalAristotle University of ThessalonikiThessaloníkiGreece
  6. 6.Department of BiochemistryHippokration General HospitalThessaloníkiGreece
  7. 7.Laboratory of the 2nd Propaedeutic Department of Internal Medicine, Hippokration General HospitalAristotle University of ThessalonikiThessaloníkiGreece
  8. 8.Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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