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



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


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.


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.


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.


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.


Adrenal insufficiency Cirrhotic cardiomyopathy Hepatoadrenal syndrome Hepatorenal syndrome 



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


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)


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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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