Post on 11-Jan-2016
description
Nonalcoholic fatty liver disease in Patients of Primary Hypothyroidism
Dr Madhukar Mittal MD, DM
Asst. Professor
Endocrine Unit, Department of Medicine
King George Medical University (earlier CSMMU)
Lucknow, India
Background
• Several endocrine disorders are known to have increased risk for Nonalcoholic fatty liver diseae (NAFLD)– Diabetes mellitus– Hypothyroidism– Adrenal insufficiency– GH deficiency– PCOS
NAFLD spectrum
• Simple steatosis• Inflammatory steatohepatitis (NASH)• Fibro-fatty Liver (Increasing levels of fibrosis)• Cirrhosis
NAFLD Prevalence
• NAFLD– 20% and 30% in Western adults1,2
– 90% in the morbidly obese3
• NASH (the more advanced form of NAFLD)– 2–3% in the general population4
– 16 and 37% in the morbidly obese3
1Browning JD et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:13872Bedogni G et al. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005;42:443Machado M et al. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol 2006;45:600–64Neuschwander-Tetri BA et al. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202
Aims and Objectives
• Study to see for prevalence of NAFLD in patients of primary hypothyroidism
• To evaluate metabolic parameters in this group of patients with NAFLD
Material and Methods
• Consecutive primary hypothyroid patients
• Tested for antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG)
• Insulin resistance assessed– Fasting insulin
– Homeostasis model assessment of insulin resistance (HOMA-IR)
– Quantitative insulin-sensitivity check index (QUICKI)
USG grading
• USG abdomen done by two radiologists to grade fatty liver
Jain KA et al. Spectrum of CT and sonographic appearance of fatty infiltration of the liver. Clin Imaging 1993;17:162Saadeh S et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 745
Tchelepi H et al. Sonography of diffuse liver disease. J Ultrasound Med 2002; 21: 1023Zwiebel WJ. Sonographic diagnosis of diffuse liver disease. Semin Ultrasound CT MR 1995;16:8
Feature at USG Score
Liver echogenicity exceeds that of renal cortex and spleen 1
Attenuation of the ultrasound wave 1
Loss of definition of the diaphragm 1
Poor delineation of the intrahepatic architecture 1
Total Maximum Score 4
NAFLD diagnosis
• NAFLD defined as– USG score >2– Fatty liver not resulting from
• Excessive alcohol consumption (>20 grams/day)• Drugs/Toxins (tamoxifen, methotrexate, amiodarone etc)• Infectious diseases (viral hepatitis etc)• Any other identifiable exogenous causes (Wilson disease,
Hemochromatosis, α-1 antitrypsin deficiency etc)
Statistical Analysis
• Data presented as mean + SD, median (interquartile range) or N (%)
• Distribution of continuous data tested for normality– Kolmogorov- Smirnov test
• Comparing between groups for continuous variable– Student T test
– Mann Whitney test for non-uniformly distributed data
• Comparing categorical data – Chi square test or Fisher exact test
• A two tailed p value <0.05 regarded as significant
• Statistical software SPSS15.0 (SPSS, Chicago, IL)
Results
Baseline Characteristics
Parameters ValuesN 71
Females, n (%) 64 (90.1)
Age (yr) 37.7 + 13.2
Age at diagnosis (yr) 35.4 + 13.1
BMI (Kg/m2) 26.6 + 6.1
TPO/TG positive, n (%) 60 (84.5)
TPO and TG, n (%) 39 (54.9)
Comaparison of thyroid antibody postive vs. antibody negative patients
Parameters TPO/TG +ve(N=60)
TPO/TG –ve(N=11)
P value
Age (yr) 36.2+13.0 46.0+14.1 0.024
Age at diagnosis (yr) 32.1+12.5 44.0+13.7 0.021
Fasting Insulin (μIU/ml) 12.47+7.11 6.27+2.92 0.014
HOMA-IR 2.90+1.72 1.30+0.77 0.010
QUICKI 0.345+0.045 0.393+0.077 0.033
BMI (Kg/m2) 26.1+5.4 25.4+6.4 0.738
FBS (mg/dl) 92.1+19.1 80.0+15.9 0.126
PPBS (mg/dl) 129.7+23.5 123.4+17.5 0.510
TG (mg/dl) 149.9+55.1 153.9+60.0 0.867
VLDL (mg/dl) 27.9+9.5 29.6+12.3 0.694
HDL (mg/dl) 40.9+12.2 48.3+12.3 0.154
NAFLD characteristics
Parameters N %No of patients 32 45.1
Females 32 100
Grade 1 17 53.1
Grade 2 14 43.8
Grade 3 1 3.1
NAFLD positive vs. NAFLD negative patientsParameters NAFLD Present
(N=32)NAFLD Absent
(N=39)P value
BMI (Kg/m2) 27.6+4.4 24.6+5.6 0.046
SBP (mm of Hg) 131.3+14.5 124.7+10.4 0.038
DBP (mm of Hg) 77.3+10.5 78.1+12.8 0.778
SGOT/AST (U/L) 42.2+15.8 36.2+13.3 0.104
SGPT/ALT (U/L) 41.0+17.3 37.4+17.0 0.629
TG (mg/dl) 174.5+74.4 146.4+79.5 0.146
VLDL (mg/dl) 30.6+10.7 25.9+7.9 0.043
HDL (mg/dl) 38.8+10.5 46.0+11.8 0.012
FBS (mg/dl) 98.2+26.6 87.2+16.4 0.041
PPBS (mg/dl) 147.4+58.1 124.7+20.2 0.029
Fasting Insulin (μIU/ml) 12.4+6.2 10.1+7.5 0.272
HOMA-IR 2.99+1.65 2.18+1.67 0.103
QUICKI 0.339+0.036 0.369+0.067 0.102
TPO or TG +ve, n (%) 28 32 0.743
Discussion
NAFLD
• Non-alcoholic fatty liver disease affects all ethnic groups
• Prevalence higher in Hispanic and European Americans compared with African-Americans
NAFLD prevalence in India
Setting N (M/F) Age Criteria Prevalence Risk Factors
Amarapurkar D et al. Annals of Hepatology 2007
Population 730 (341/389)
>20yr USG 18.9%(M/F 24.6%/13.6%)
Age>40MaleCentral ObesityBMI>25Increased FBS
Uchil D et al. JAPI 2009
Hospital 1003 (565/438)
18-60yr USG 22.6%(M/F 29%/13.9%)
waist circumference TG, Low HDL-c, Blood pressure, FBS
Singh SP et al. Trop Gastroenterol 2004
Population 159 USG 24.5% (M/F 26.9%/13.8%)
BMI
NAFLD was seen in around half of hypothyroid patients
Chung GE et al.
• 2324 cases of hypothyroidism (overt and subclinical)
• NAFLD based on USG• 62% female• NAFLD prevalence 30.2%
Non-alcoholic fatty liver disease across the spectrum of hypothyroidism.J Hepatol. 2012 Jul;57(1):150-6
Thyroid antibody positivity
Thyroid antibody positivity correlated with higher markers of insulin resistance
Parameters TPO/TG +ve(N=60)
TPO/TG –ve(N=11)
P value
Age (yr) 36.2+13.0 46.0+14.1 0.024
Age at diagnosis (yr) 32.1+12.5 44.0+13.7 0.021
Fasting Insulin 12.47+7.11 6.27+2.92 0.014
HOMA-IR 2.90+1.72 1.30+0.77 0.010
QUICKI 0.345+0.045 0.393+0.077 0.033
• Low normal FT4 levels were significantly
associated with increased insulin resistance
Roos A et al. J Clin Endocrinol Metab
2007;92(2):491
NAFLD in hypothyroidism and metabolic characteristics
Patients who had NAFLD had higher systolic blood pressure and deranged metabolic parameters (higher BMI, FBS, PPBS, VLDL and low
HDL)
Parameters NAFLD Present(N=32)
NAFLD Absent (N=39)
P value
BMI (Kg/m2) 27.6+4.4 24.6+5.6 0.046
SBP (mm of Hg) 131.3+14.5 124.7+10.4 0.038
VLDL 30.6+10.7 25.9+7.9 0.043
HDL 38.8+10.5 46.0+11.8 0.012
FBS 98.2+26.6 87.2+16.4 0.041
PPBS 147.4+58.1 124.7+20.2 0.029
Fasting Insulin 12.4+6.2 10.1+7.5 0.272
HOMA-IR 2.99+1.65 2.18+1.67 0.103
QUICKI 0.339+0.036 0.369+0.067 0.102
Health ABC study. Waring CA et al. Clin Endocrinol 2012;76(6):911
• 2119 patients• 684 initially identified with metabolic syndrome• Higher TSH levels and subclinical
hypothyroidism with TSH>10 mIU/L significantly associated with prevalent metabolic syndrome
• Each unit increase in TSH associated with 3% increase in odds of prevalent metabolic syndrome
Thyroid function and prevalent and incident metabolic syndrome in older adults: the health, ageing and body composition (Health ABC) study. Warin CA et al. Clin Endocrinol 2012;76(6):911
Conclusion
• NAFLD seen in nearly half of primary hypothyroid patients
• Insulin resistance higher in thyroid antibody positive patients
• NAFLD associated with increased clustering of parameters of metabolic syndrome
Limitations
• Histopathology (Liver Biopsy) not done– USG cannot differentiate between Simple Steatosis
and NASH
• Larger sample size needed
Future Course
• Ongoing study• Currently 142 patients included• Noninvasive markers for liver cirrhosis
– AST to platelet ratio index (APRI)– AST/ALT ratio (AAR)– BARD score
Acknowledgement
• Dr Neha Jain• Dr Anit Parihar• Dr Vivek Kumar• Dr Ravi Misra• Dr AK Vaish
Thank You
King George Medical University, Lucknow
S No Female (n=64) Male (n=7) P value
Age of patient 37.18+12.93 42.14+15.52 .352
Age at diagnosis 34.64+12.81 41.57+15.16 .191
BMI 27.23+6.04 21.75+4.28 .020
height 152.54+7.45 162+8.87 .001
weight 63.48+15.03 57.85+12.28 .346
Systolic BP 128.92+14.07 125.14+13.26 .502
Dystolic BP 78.21+10.88 81.71+24.21 .498
Initial TSH 33.66+48.06 22.03+20.98 .532
TPO 807.06+890.20 275.02+509.44 .163
TG 202.44+316.34 66.64+82.92 .060
S. bilirubin 1.06+2.00 1.01 +0.45 .945
SGOT 44.50+29.59 33.00+6.24 .313
SGPT 47.78+44.16 32.14+6.25 .357
SALP 194.17+101.14 190.85+58.94 .933
CHO 189.77+46.58 178.42+61.75 .563
TG 155.69+55.87 179.57+107.79 .353
LDL 108.69+42.30 103.50+22.48 .770
HDL 42.13+11.69 42.28+10.09 .970
VLDL 28.77+9.58 27.29+9.50 .702
Fasting insulin 12.78+7.93 8.37+3.13 .153
Fasting blood sugar 90.28+18.36 91.42+15.93 .876
Post prandial sugar 127.86+20.75 134.42+23.03 .441
Platelet count 1.66+0.68 1.58+0.75 .803
MCV 85.15+8.58 88.84+11.29
MCH 27.78+3.68 30.57+4.04
MCHC 31.79+2.21 33.71+2.14
MMSE 27.02+2.00 28.00+1.15 .211
HAMD 14.64+6.07 13.00+5.48 .499
SGOT/SGPT=AAR 1.11+0.39 1.05+0.24 .719
BARD 2.21+0.87 2.00+1.00 .555
AST/platelet=APRI 1.85+1.46 1.31+0.72 .335
HOMA 2.75+1.83 1.97+0.96 .278
33. QUICKI 1.52+0.32 1.40+0.16 .348
• NASH was first coined by Ludwig et al. in 1980• the prevalence of NAFLD has risen rapidly in
parallel with the dramatic rise in population levels of obesity and diabetes, resulting in NAFLD now representing the most common cause of liver disease in the Western world