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Urinary free cortisol is a reliable index of adrenal cortisol production in patients with liver cirrhosis

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Abstract

Background

The measurement of total and free cortisol has been studied as a clinical index of adrenal cortisol production in patients with liver cirrhosis. Correlations between free plasma and salivary cortisol have previously been reported in stable cirrhotic patients. Urinary free cortisol constitutes an index of adrenal cortisol production; however, it has never been used in assessing adrenal function in patients with liver cirrhosis.

Aims

The aim of this observational study was to determine associations between urinary free cortisol, serum total, salivary, measured and calculated plasma free cortisol levels in cirrhotics, determining which of them can be used as an indirect index of free cortisol levels. Moreover, we investigated the potential use of 24 h urinary free cortisol as a prognostic factor for mortality.

Methods

Seventy-eight outpatients with liver cirrhosis were included. Serum, salivary and urinary free cortisol were measured using the electrochemiluminenscence immunoassay. Plasma free cortisol determination was conducted using a single quadrupole mass spectrometer. The quantification of free cortisol was achieved by determining the signal response on negative ESI-MS mode.

Results

Twenty-four hour urinary free cortisol levels correlated with free cortisol determined by mass spectrometer, total cortisol and calculated free cortisol levels. Patients with low levels of urinary free cortisol presented a significantly higher mortality rate compared to those with high levels. The factors associated with death risk were determined by Cox regression. In the multivariate analysis, two models were applied; in the first model, CP score, PVT and urinary free cortisol were found to be significantly related to patients’ survival, whereas in the second, MELD score, ascites and urinary free cortisol were independently related to survival.

Conclusions

This study suggests that 24 h urinary free cortisol could be considered as a potential index of adrenal cortisol production in patients with liver cirrhosis and it potentially detects patients with a high mortality risk.

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Funding

This work has been supported by “Hellenic Association for the Study of the Liver”.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras, Greece

    Maria Michailidou, Ioanna Aggeletopoulou, Konstantinos Zisimopoulos, Efthymios P. Tsounis, Katerina Karaivazoglou, Evanthia Tourkochristou, Georgia Diamantopoulou, Konstantinos Thomopoulos & Christos Triantos

  2. Laboratory of Pharmaceutical Analysis, Department of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Maria Kouskoura, Nikolaos Koutras & Catherine K. Markopoulou

  3. Department of Biochemistry, University Hospital of Patras, Patras, Greece

    Martha Mandellou

  4. Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Internal Medicine, University of Patras, Patras, Greece

    Marina Michalaki

  5. Department of Internal Medicine, University Hospital of Patras, Patras, Greece

    Charalampos Gogos & Dimitrios Velissaris

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  1. Maria Michailidou
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Contributions

M. Michailidou: acquisition of data and analysis and interpretation of data; I.A.: acquisition of data, analysis and interpretation of data, and drafting of the manuscript; M.K. and K.Z.: acquisition of data and analysis and interpretation of data; E.P.T. and K.K.: analysis and interpretation of data, statistical analysis; E.T.: analysis and interpretation of data; M. Mandellou and G.D.: acquisition of data; N.K.: analysis of data; M. Michalaki, C.G., D.V., C.K.M., and K.T.: analysis and interpretation of data, critical revision of the manuscript for important intellectual content; C.T.: study concept and design, drafting of the manuscript, critical revision of the manuscript for important intellectual content, final approval of the version to be published. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed.

Corresponding author

Correspondence to Christos Triantos.

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The authors declare no competing interests.

Ethical approval

All study participants, or their legal guardian, provided informed written consent prior to study enrollment. The study protocol was reviewed and approved by the Ethics committee of the University Hospital of Patras. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki for medical research involving human subjects. All the experiments were performed in accordance with relevant guidelines and regulations of the concerned Ethics committee.

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Michailidou, M., Aggeletopoulou, I., Kouskoura, M. et al. Urinary free cortisol is a reliable index of adrenal cortisol production in patients with liver cirrhosis. Endocrine 76, 697–708 (2022). https://doi.org/10.1007/s12020-022-03055-2

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