Introduction
Relative adrenal insufficiency (RAI) is a syndrome characterized by decreased production of cortisol with respect to peripheral demands.1
Cortisol is a steroid hormone that regulates metabolism and immune system, maintenance of vascular tone and inhibition of production of proinflammatory cytokines and adhesion molecule expressions.2
Over 90% of circulating cortisol is bound to Corticosteroid binding globulin (CBG) (also called transcortin) and albumin, with less than 10% in the free biologically active form.3
To assess the severity of the liver disease, scoring models have been used. The oldest model is the Child-Pugh classification.4
A recent model has been developed for the assessment of prognosis which is the Model of End-stage Liver Disease (MELD) score.5 In this model there are only objective parameters, bilirubin, prothrombin time and creatinine. It is used to calculate mortality risk for patients with end-stage live r disease.6,7
The percentage of AI in cirrhotic patients varies among different studies and depends on different methods and criteria used to evaluate adrenal function.8
With SD-SST, the prevalence of AI in terminally ill cirrhotic patients varied between 10%9 to 87%10
With LD-SST, the prevalence of AI in terminally ill cirrhotic patients varied between 33%11 and 60%.12
Adrenal insufficiency (AI) has been described in all stages of cirrhotic patients.13 However, the exact mechanism leading to AI in cirrhotic population is not yet known. It is known that cholesterol is an important substrate for steroid synthesis and adrenal glands synthesize cortisol whenever is necessary. In cirrhosis, the adrenal glands synthesize the reduced amount of cortisol especially under stress conditions leading to “adrenal exhaustion syndrome” ending to AI.14
The mechanism of action of ACTH is through binding to a seven-membrane-spanning G protein-coupled ACTH receptor.15
Upon ligand binding, the receptor undergoes conformational changes that stimulate adenylyl cyclase, which further leads to an increase in intracellular cAMP and subsequent activation of protein kinase A. It stimulates lipoprotein uptake into cortical cells. This stimulates transcription of the genes coding for P450scc, steroid 11β-hydroxylase, and their associated electron transfer proteins.16
Materials and Methods
Source of data
Patients admitted in medicine/gastroenterology ward of DMC&H
50 consecutive patients of cirrhosis were included in the study.
Inclusion criteria
Diagnosed patients of cirrhosis based on clinical/ biochemical / radiological/ endoscopy and or liver biopsy.
Exclusion criteria
HIV/Immunodeficiency
Severe chronic heart disease
Chronic obstructive lung disease
Chronic hemodialysis
Severe sepsis or septic shock.
Patients on steroid therapy
Depending upon the levels of cortisol, patients were divided into 3 groups:
Group I Patients having > 15 μg /dl cortisol (Baseline levels) n=31
Group II Patients having 3 -15 μg /dl cortisol (Baseline levels) n=11
Group III Patients having < 3 μg /dl cortisol (Baseline levels) n=8
In Group II, ACTH Stimulation (SD-SST) was done, then this Group was further divided into II a and II b
II a Patients having >18 μg /dl cortisol levels 30 minutes after ACTH stimulation (n=5)
II b Patients having <18 μg /dl cortisol levels 30 minutes after ACTH stimulation (n=6)
Diagnostic criteria for Adrenal Insufficiency
Levels of serum cortisol at 6-10 am <3µg/ dI confirms Adrenal Insufficiency.
Levels of serum cortisol at 6-10 am >15µg/ dI rules out Adrenal Insufficiency
Intermediate cortisol levels at 6-10 am are 3-15 µg/dl.
ACTH Stimulation were performed for intermediate cortisol levels. The diagnosis of adrenal insufficiency was considered if the serum cortisol level is <18µg/ dI, 30 minutes after stimulation.17
All the 50 patients were diagnosed on ultrasound findings.
Liver function tests were done in all the patients
Table 1
Child-Turcotte-Pugh scoring system
Group A- CTP Score (5-6)
MELD Score: Model for End-Stage Liver Disease.
3.8(loge serum bilirubin mg/dl) +11.2(loge INR) +9.6(loge serum creatinine mg/dl) +6.4.
Statistical analysis
The data was analyzed using Microsoft excel and SPSS version 20.0 (IBM SPSS, Chicago, Illinois). Mean and standard deviation were computed for the variables. The comparison between groups were done by Chi square and ANOVA. P value ≤ 0.005 was taken as significant.
Distribution of subjects according to adrenal function
Out of 50 patients included in this study, 14 (28%) patients had Adrenal Insufficiency
Table 2
Distribution of subjects according to BMI
Out of 50 patients enrolled, 37 patients had BMI > 23. All the Adrenal insufficient patients had BMI ≥ 23. All the patients with BMI< 23 were in Group I. A significant relationship was found between cortisol levels and BMI (p=0.007).
Discussion
The prevalence of AI in Cirrhosis was 28% in our study. Acevedo et al18 reported 26% AI. Galbois et al19 reported 33% AI prevalence whereas other studies reported higher prevalence of AI.20
Prevalence varies according to choice of subjects in different studies. Higher prevalence of AI was found in studies that included subjects with liver failure, liver transplant recipients and critically ill cirrhotic patients as compared to studies with stable cirrhotic patients. The percentage of AI in cirrhotic patients varies among different studies and depends on the different methods used to estimate adrenal function.
Out of 50 patients enrolled, 37 patients had BMI > 23. All the Adrenal insufficient patients had BMI ≥ 23. All the patients with BMI< 23 were in Group I. A significant relationship was found between cortisol levels and BMI (p=0.007).
Higher the BMI, lesser the value of serum cortisol. Therefore there was inverse relationship between serum cortisol levels and BMI.
A cause- effect relationship between obesity and cortisol levels is not clearly known, it may be either due to altered hypothalamic-pituitary-adrenal axis in obesity or due to enchanced metabolic clearance of cortisol in obesity.
