Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients?

December 8, 2021 updated by: Zachary Henry, MD, University of Virginia

The hepatoadrenal syndrome has been well described in the literature and is known to be associated with poorer outcomes in both stable and critically ill cirrhotic patients. In chronic liver disease, adrenal (and more specifically cortisol) insufficiency is thought to be a byproduct of altered lipid metabolism that results in decreased HDL production and thus decreased delivery of cholesterol to the adrenal for subsequent corticosteroid production. Studies to date have implicated lecithin-cholesterol acetyltransferase (LCAT) as the key enzyme which is deficient in some cirrhotic patients, leading to an impaired ability to esterify cholesterol and thus a loss of normal cellular functioning and membrane stability. The investigators seek to quantify this LCAT deficiency in a cohort of cirrhotic patients and demonstrate its association with various abnormal physiologies associated with chronic liver disease, including spur cell anemia, low HDL levels, and adrenal insufficiency.

Hospitalized cirrhotic patients at UVA that meet study eligibility criteria will be approached by a member of the study team to obtain consent for participation. If a patient agrees to become a study subject, they will have an approximate total of 35ml of blood drawn the following morning. Lab tests to be performed include: peripheral blood smear, lipid panel, free cortisol, cortisol binding globulin, serum cholesterol esters (surrogate for LCAT enzyme activity), and a standard-dose cortisol stimulation test. The latter involves blood drawn with the initial collection, administration of an intravenous 250mcg dose of synthetic ACTH, and then repeat small-volume blood draws at 30 minutes and 60 minutes later.

Subjects will be classified as adrenally sufficient or insufficient on the basis of as standard-dose cortisol stimulation test. Variables of interest for comparison between the groups include MELD score, Child-Turcotte-Pugh (CTP) classification, high-density lipoprotein (HDL) levels, presence of spur cell anemia, serum cholesterol ester percentage (surrogate for LCAT enzymatic activity), cortisol binding globulin levels, and free cortisol levels. Student's t-test and Chi Square tests will be utilized to determine significance; a p <0.05 value will be used as our threshold for significance. If multiple factors are found to be significantly different in a univariate fashion between classification groups, a multivariate logistic regression analysis will be performed for adjusted analysis. The investigators will also seek to define any correlations between variables. Furthermore, the investigators will assess correlation between MELD score and serum cholesterol ester percentage, spur cell anemia, HDL levels, cortisol binding globulin levels, and free cortisol levels; similar correlate analysis will be done using CTP classification instead of MELD score.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 110 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age >=18 years
  • Diagnosis of cirrhosis
  • Admission to hospital

Exclusion Criteria:

  • Age < 18 years
  • Prior enrollment in study (i.e. readmission)
  • Prisoner
  • Pregnancy
  • Prednisone or Hydrocortisone use in last 24 hours

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hospitalized cirrhosis patients
Administration of cortisol stimulation test to assess for presence or absence of adrenal insufficiency
Drug: Cosyntropin
Administer 250mcg cosyntropin to hospitalized cirrhosis patients to assess for the presence of adrenal insufficiency

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Cholesterol Esterification Deficiency
Time Frame: 24 hours
A percent quantification of serum cholesterol esterification will be measured via blood draw. Low values represent deficiency in esterification, which is a surrogate measure of lecthicin-cholesterol acetyltransferase (LCAT) enzymatic deficiency.
24 hours
Number of Participants With Spur Cell Anemia
Time Frame: 24 hours
A peripheral blood smear will be obtained and assessed for presence of acanthocytes (spur cells). Spur cell anemia is defined as a serum hemoglobin < 10g/dL and the presence of >= 5% spur cells on blood smear.
24 hours
Participant Transplant-Free Survival
Time Frame: 6 months
Transplant and Death are considered equivalent outcomes
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Relative Adrenal Insufficiency (RAI)
Time Frame: 24 hours
A baseline total cortisol level will be obtained and then patients will receive a standard-dose synthetic ACTH (250mcg of Cosyntropin) stimulation test to assess for the presence of adrenal insufficiency. RAI is defined as a change in the total cortisol level in response to the stimulation test of <9mcg/dL when measured 60 minutes after the Cosyntropin is administered.
24 hours
Number of Participants With Low Free Cortisol
Time Frame: 24 hours
Patients will have their free cortisol levels measured to assess for deficiency.
24 hours
Number of Participants Who Received Liver Transplantation at 90 Days
Time Frame: 90 days
Patients who received a liver transplant within 90 days of enrollment
90 days
Number of Participants Who Received Liver Transplantation at 6 Months
Time Frame: 6 months
Patients who received a liver transplant within 6 months of enrollment
6 months
Number of Participants Who Died Within Index Hospitalization
Time Frame: Within Hospitalization
Patients who died within the same hospitalization as enrollment
Within Hospitalization
Number of Participants Who Died at 30 Days
Time Frame: 30 days
Patients who died within 30 days of enrollment
30 days
Number of Participants Who Died at 90 Days
Time Frame: 90 days
Patients who died within 90 days of enrollment
90 days
Number of Participants Who Died at 6 Months
Time Frame: 6 months
Patients who died within 6 months of enrollment
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Virginia

Investigators

  • Principal Investigator: Zachary Henry, MD, University of Virginia School of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 29, 2018

Primary Completion (Actual)

March 12, 2019

Study Completion (Actual)

March 12, 2019

Study Registration Dates

First Submitted

November 20, 2017

First Submitted That Met QC Criteria

December 8, 2017

First Posted (Actual)

December 11, 2017

Study Record Updates

Last Update Posted (Actual)

December 9, 2021

Last Update Submitted That Met QC Criteria

December 8, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20212

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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