Defining the Mechanisms Underlying Adrenal Insufficiency in Cirrhosis

Study Overview
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Brief Summary
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This study aims to define the prevalence and potential pathophysiologic mechanisms underlying relative adrenal insufficiency (RAI) in outpatients with decompensated cirrhosis. Patients will be followed prospectively for up to two years to determine incidence of RAI, whether RAI represents a permanent or dynamic physiologic state in cirrhosis, and to determine whether RAI in this setting is associated with important clinical outcomes.

Official Title
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Defining the Mechanisms Underlying Adrenal Dysfunction in Cirrhosis and Its Prognostic Significance

Conditions
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Cirrhosis, Adrenal Insufficiency

Intervention / Treatment
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* Drug: Cosyntropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18y Diagnosis of cirrhosis by biopsy or compatible clinical picture Experienced at least one portal decompensating event in the past and currently have a Child-Pugh B or C classification Exclusion Criteria: Pregnant women Prisoners Not been treated with medication known to affect the adrenal axis within the past 4 weeks (oral or IV steroids, ketoconazole, etomidate) Hospitalized at time of enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RAI<br>Subjects will be diagnosed with relative adrenal insufficiency as determined by administration of a standard-dose ACTH stimulation test (0.25mg Cosyntropin) and an increase in serum total cortisol <9mcg/dL. | Drug: Cosyntropin<br>* Administer 0.25mg Cosyntropin to determine adrenal sufficiency vs. insufficiency in patients with decompensated cirrhosis<br>|
| Non-RAI<br>Subjects will have not have relative adrenal insufficiency as determined by administration of a standard-dose ACTH stimulation test (0.25mg Cosyntropin) and an increase in serum total cortisol >= 9mcg/dL. | Drug: Cosyntropin<br>* Administer 0.25mg Cosyntropin to determine adrenal sufficiency vs. insufficiency in patients with decompensated cirrhosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RAI prevalence |  | 1 year | 
| Baseline Cholesterol Esterification Percentage |  | baseline | 
| 6 month Cholesterol Esterification Percentage |  | 6 months | 
| 12 month Cholesterol Esterification Percentage |  | 12 months | 
| 18 month Cholesterol Esterification Percentage |  | 18 months | 
| 24 month Cholesterol Esterification Percentage |  | 24 months | 
| Baseline 17-OH Progesterone Level |  | baseline | 
| 6 month 17-OH Progesterone Level |  | 6 month | 
| 12 month 17-OH Progesterone Level |  | 12 months | 
| 18 month 17-OH Progesterone Level |  | 18 months | 
| 24 month 17-OH Progesterone Level |  | 24 months | 
| Baseline ACTH level |  | baseline | 
| 6 month ACTH level |  | 6 months | 
| 12 month ACTH level |  | 12 months | 
| 18 month ACTH level |  | 18 months | 
| 24 month ACTH level |  | 24 months | 
| Baseline IL-1 Level |  | baseline | 
| 6 month IL-1 Level |  | 6 months | 
| 12 month IL-1 Level |  | 12 months | 
| 18 month IL-1 Level |  | 18 months | 
| 24 month IL-1 Level |  | 24 months | 
| Baseline Plasma Renin Activity |  | baseline | 
| 6 month Plasma Renin Activity |  | 6 month | 
| 12 month Plasma Renin Activity |  | 12 month | 
| 18 month Plasma Renin Activity |  | 18 month | 
| 24 month Plasma Renin Activity |  | 24 month | 
| Baseline serum normetanephrine level |  | baseline | 
| 6 month serum normetanephrine level |  | 6 month | 
| 12 month serum normetanephrine level |  | 12 month | 
| 18 month serum normetanephrine level |  | 18 month | 
| 24 month serum normetanephrine level |  | 24 month | 
| Baseline 11-deoxycortisol level |  | baseline | 
| 6 month 11-deoxycortisol level |  | 6 months | 
| 12 month 11-deoxycortisol level |  | 12 months | 
| 18 month 11-deoxycortisol level |  | 18 months | 
| 24 month 11-deoxycortisol level |  | 24 months | 
| Baseline HDL level |  | baseline | 
| 6 month HDL level |  | 6 months | 
| 12 month HDL level |  | 12 months | 
| 18 month HDL level |  | 18 months | 
| 24 month HDL level |  | 24 months | 
| Baseline IL-6 level |  | baseline | 
| 6 month IL-6 level |  | 6 months | 
| 12 month IL-6 level |  | 12 months | 
| 18 month IL-6 level |  | 18 months | 
| 24 month IL-6 level |  | 24 months | 
| Baseline IL-10 level |  | baseline | 
| 6 month IL-10 level |  | 6 months | 
| 12 month IL-10 level |  | 12 months | 
| 18 month IL-10 level |  | 18 months | 
| 24 month IL-10 level |  | 24 months | 
| Baseline TNFa level |  | baseline | 
| 6 month TNFa level |  | 6 months | 
| 12 month TNFa level |  | 12 months | 
| 18 month TNFa level |  | 18 months | 
| 24 month TNFa level |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Incidence of RAI |  | over two years | 
| 30-day transplant-free survival |  | 30 days | 
| 90-day transplant-free survival |  | 90 days | 
| 6-month transplant-free survival |  | 6 months | 
| 1 year transplant-free survival |  | 1 year | 
| 2 year transplant-free survival |  | 2 years | 
| 30 day new or worsened portal hypertensive decompensation |  | 30 days | 
| 90 day new or worsened portal hypertensive decompensation |  | 90 days | 
| 6 month new or worsened portal hypertensive decompensation |  | 6 months | 
| 1 year new or worsened portal hypertensive decompensation |  | 1 year | 
| 2 year new or worsened portal hypertensive decompensation |  | 2 years | 
| 30 day unplanned hospitalization |  | 30 days | 
| 90 day unplanned hospitalization |  | 90 days | 
| 6 month unplanned hospitalization |  | 6 month | 
| 1 year unplanned hospitalization |  | 1 year | 
| 2 year unplanned hospitalization |  | 2 year |