Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients?

Phase 3

Completed

Conditions: Cirrhosis
Adrenal Insufficiency
Spur Cell Anemia
Lecithin Acyltransferase Deficiency

Interventions: Drug: Cosyntropin

Registration Number: NCT03368066

Lead Sponsor: University of Virginia

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hospitalized cirrhosis patients	Cosyntropin	Administration of cortisol stimulation test to assess for presence or absence of adrenal insufficiency

Primary Outcome Measures

Name	Time	Method
Number of Participants With Cholesterol Esterification Deficiency	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.
Number of Participants With Spur Cell Anemia	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.
Participant Transplant-Free Survival	6 months	Transplant and Death are considered equivalent outcomes

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Relative Adrenal Insufficiency (RAI)	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.
Number of Participants Who Received Liver Transplantation at 6 Months	6 months	Patients who received a liver transplant within 6 months of enrollment
Number of Participants Who Died at 6 Months	6 months	Patients who died within 6 months of enrollment
Number of Participants With Low Free Cortisol	24 hours	Patients will have their free cortisol levels measured to assess for deficiency.
Number of Participants Who Received Liver Transplantation at 90 Days	90 days	Patients who received a liver transplant within 90 days of enrollment
Number of Participants Who Died Within Index Hospitalization	Within Hospitalization	Patients who died within the same hospitalization as enrollment
Number of Participants Who Died at 30 Days	30 days	Patients who died within 30 days of enrollment
Number of Participants Who Died at 90 Days	90 days	Patients who died within 90 days of enrollment