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Prevalence of Hypothyroidism in Nonalcoholic Fatty Liver Disease

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Abstract

Background

A possible association between nonalcoholic fatty liver disease (NAFLD) and hypothyroidism has been suggested. The recognized link between hypothyroidism and elements of the metabolic syndrome may explain this association.

Aim

The purpose of this study was to determine the prevalence of hypothyroidism in a cohort of patients with NAFLD and analyze the potential factors associated with hypothyroidism in this patient population.

Methods

Two hundred forty-six patients with biopsy-proven NAFLD attending hepatology clinics at the Cleveland Clinic between October 2006 and June 2009, and 430 age-, gender-, race- and BMI-matched control subjects seen in the general internal medicine clinic were included. Patients with a clinical diagnosis of hypothyroidism who were on thyroid replacement therapy were considered to be hypothyroid.

Results

Hypothyroidism was more frequent among patients with NAFLD (21% vs. 9.5%; P < 0.01) compared to controls, and was higher in NASH patients than NAFLD patients without NASH (25% vs. 12.8%, P = 0.03). Subjects with hypothyroidism were 2.1 (95% CI 1.1–3.9, P = 0.02) and 3.8 (95% CI 2–6.9, P < 0.001) times more likely to have NAFLD and NASH, respectively. By multivariate analysis, female gender (P < 0.001) and increased BMI (P = 0.03) were associated with hypothyroidism. NAFLD subjects who reported mild alcohol consumption were less likely to have hypothyroidism compared to those who reported complete abstinence (OR 0.37, P = 0.008).

Conclusions

A higher prevalence of hypothyroidism was demonstrated in patients with NAFLD compared to controls. Among subjects with NALFD, female gender, increased BMI and history of abstinence from alcohol were associated with hypothyroidism. Patients with hypothyroidism were also more likely to have NASH.

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References

  1. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395.

    Article  PubMed  Google Scholar 

  2. Dimitriadis G, Mitrou P, Lambadiari V, et al. Insulin action in adipose tissue and muscle in hypothyroidism. J Clin Endocrinol Metab. 2006;91:4930–4937.

    Article  PubMed  CAS  Google Scholar 

  3. Rochon C, Tauveron I, Dejax C, et al. Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism. Clin Sci (Lond). 2003;104:7–15.

    Article  CAS  Google Scholar 

  4. Pucci E, Chiovato L, Pinchera A. Thyroid and lipid metabolism. Int J Obes Relat Metab Disord. 2000;24:S109–S112.

    PubMed  CAS  Google Scholar 

  5. O’Brien T, Dinneen SF, O’Brien PC, Palumbo PJ. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc. 1993;68:860–866.

    PubMed  Google Scholar 

  6. Michalaki MA, Vagenakis AG, Leonardou AS, et al. Thyroid function in humans with morbid obesity. Thyroid. 2006;16:73–78.

    Article  PubMed  CAS  Google Scholar 

  7. Raftopoulos Y, Gagne DJ, Papasavas P, et al. Improvement of hypothyroidism after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Obes Surg. 2004;14:509–513.

    Article  PubMed  Google Scholar 

  8. Liangpunsakul S, Chalasani N. Is hypothyroidism a risk factor for non-alcoholic steatohepatitis? J Clin Gastroenterol. 2003;37:340–343.

    Article  PubMed  Google Scholar 

  9. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321.

    Article  PubMed  Google Scholar 

  10. Aoki Y, Belin RM, Clickner R, Jeffries R, Phillips L, Mahaffey KR. Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999–2002). Thyroid. 2007;17:1211–1223.

    Article  PubMed  Google Scholar 

  11. Bindels AJ, Westendorp RG, Frolich M, Seidell JC, Blokstra A, Smelt AH. The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding? Clin Endocrinol (Oxf). 1999;50:217–220.

    Article  CAS  Google Scholar 

  12. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:526–534.

    Article  PubMed  CAS  Google Scholar 

  13. Bjoro T, Holmen J, Kruger O, et al. Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT). Eur J Endocrinol. 2000;143:639–647.

    Article  PubMed  CAS  Google Scholar 

  14. Ayala C, Cozar MV, Rodriguez JR, Silva H, Pereira JL, Garcia-Luna PP. Subclinical thyroid disease in institutionalised healthy geriatric population. Med Clin (Barc). 2001;117:534–535.

    CAS  Google Scholar 

  15. Silveira MG, Mendes FD, Diehl NN, Enders FT, Lindor KD. Thyroid dysfunction in primary biliary cirrhosis, primary sclerosing cholangitis and non-alcoholic fatty liver disease. Liver Int. 2009;29:1094–1100.

    Article  PubMed  CAS  Google Scholar 

  16. Kosovskii MI, Katkova SP, Mirakhmedov MM, Rakhimdzhanov RT. Insulin resistance in experimental hypo- and hyperthyroidism. Probl Endokrinol (Mosk). 1989;35:50–54.

    CAS  Google Scholar 

  17. Shantha GP, Kumar AA, Jeyachandran V, et al. Association between primary hypothyroidism and metabolic syndrome and the role of C reactive protein: a cross-sectional study from South India. Thyroid Res. 2009;2:2.

    Article  PubMed  Google Scholar 

  18. Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001;50:1844–1850.

    Article  PubMed  CAS  Google Scholar 

  19. Dimitriadis G, Parry-Billings M, Bevan S, et al. The effects of insulin on transport and metabolism of glucose in skeletal muscle from hyperthyroid and hypothyroid rats. Eur J Clin Invest. 1997;27:475–483.

    Article  PubMed  CAS  Google Scholar 

  20. Dimitriadis GD, Leighton B, Parry-Billings M, West D, Newsholme EA. Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat. Biochem J. 1989;257:369–373.

    PubMed  CAS  Google Scholar 

  21. Smithson MJ. Screening for thyroid dysfunction in a community population of diabetic patients. Diabet Med. 1998;15:148–150.

    Article  PubMed  CAS  Google Scholar 

  22. Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology. 2005;42:987–1000.

    Article  PubMed  CAS  Google Scholar 

  23. Krotkiewski M. Thyroid hormones and treatment of obesity. Int J Obes Relat Metab Disord. 2000;24:S116–S119.

    Article  PubMed  CAS  Google Scholar 

  24. Vettor R. The metabolic actions of thyroid hormone and leptin: a mandatory interplay or not? Diabetologia. 2005;48:621–623.

    Article  PubMed  CAS  Google Scholar 

  25. Leonhardt U, Ritzel U, Schafer G, Becker W, Ramadori G. Serum leptin levels in hypo- and hyperthyroidism. J Endocrinol. 1998;157:75–79.

    Article  PubMed  CAS  Google Scholar 

  26. Saxena NK, Ikeda K, Rockey DC, Friedman SL, Anania FA. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology. 2002;35:762–771.

    Article  PubMed  CAS  Google Scholar 

  27. Benomar Y, Wetzler S, Larue-Achagiotis C, Djiane J, Tome D, Taouis M. In vivo leptin infusion impairs insulin and leptin signalling in liver and hypothalamus. Mol Cell Endocrinol. 2005;242:59–66.

    Article  PubMed  CAS  Google Scholar 

  28. Luboshitzky R, Aviv A, Herer P, Lavie L. Risk factors for cardiovascular disease in women with subclinical hypothyroidism. Thyroid. 2002;12:421–425.

    Article  PubMed  Google Scholar 

  29. Obuobie K, Smith J, Evans LM, John R, Davies JS, Lazarus JH. Increased central arterial stiffness in hypothyroidism. J Clin Endocrinol Metab. 2002;87:4662–4666.

    Article  PubMed  CAS  Google Scholar 

  30. Villanova N, Moscatiello S, Ramilli S, et al. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005;42:473–480.

    Article  PubMed  Google Scholar 

  31. Pearce EN. Hypothyroidism and dyslipidemia: modern concepts and approaches. Curr Cardiol Rep. 2004;6:451–456.

    Article  PubMed  Google Scholar 

  32. Toledo FG, Sniderman AD, Kelley DE. Influence of hepatic steatosis (fatty liver) on severity and composition of dyslipidemia in type 2 diabetes. Diabetes Care. 2006;29:1845–1850.

    Article  PubMed  Google Scholar 

  33. Cable EE, Finn PD, Stebbins JW, et al. Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonist. Hepatology. 2009;49:407–417.

    Article  PubMed  CAS  Google Scholar 

  34. Hermann D, Heinz A, Mann K. Dysregulation of the hypothalamic-pituitary-thyroid axis in alcoholism. Addiction. 2002;97:1369–1381.

    Article  PubMed  Google Scholar 

  35. Hegedus L, Rasmussen N, Ravn V, Kastrup J, Krogsgaard K, Aldershvile J. Independent effects of liver disease and chronic alcoholism on thyroid function and size: the possibility of a toxic effect of alcohol on the thyroid gland. Metabolism. 1988;37:229–233.

    Article  PubMed  CAS  Google Scholar 

  36. Knudsen N, Bulow I, Laurberg P, Perrild H, Ovesen L, Jorgensen T. Alcohol consumption is associated with reduced prevalence of goitre and solitary thyroid nodules. Clin Endocrinol (Oxf). 2001;55:41–46.

    Article  CAS  Google Scholar 

  37. Allen NE, Beral V, Casabonne D, et al. Moderate alcohol intake and cancer incidence in women. J Natl Cancer Inst. 2009;101:296–305.

    Article  PubMed  Google Scholar 

  38. Facchini F, Chen YD, Reaven GM. Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity. Diabetes Care. 1994;17:115–119.

    Article  PubMed  CAS  Google Scholar 

  39. Freiberg MS, Cabral HJ, Heeren TC, Vasan RS, Curtis Ellison R. Third National Health and Nutrition Examination Survey. Alcohol consumption and the prevalence of the metabolic syndrome in the US: a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey. Diabetes Care. 2004;27:2954–2959.

    Article  PubMed  Google Scholar 

  40. Nanda N, Bobby Z, Hamide A, Koner BC, Sridhar MG. Association between oxidative stress and coronary lipid risk factors in hypothyroid women is independent of body mass index. Metabolism. 2007;56:1350–1355.

    Article  PubMed  CAS  Google Scholar 

  41. Baskol G, Atmaca H, Tanriverdi F, Baskol M, Kocer D, Bayram F. Oxidative stress and enzymatic antioxidant status in patients with hypothyroidism before and after treatment. Exp Clin Endocrinol Diabetes. 2007;115:522–526.

    Article  PubMed  CAS  Google Scholar 

  42. Sanyal AJ, Campbell-Sargent C, Mirshahi F, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001;120:1183–1192.

    Article  PubMed  CAS  Google Scholar 

  43. Begriche K, Igoudjil A, Pessayre D, Fromenty B. Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. Mitochondrion. 2006;6:1–28.

    Article  PubMed  CAS  Google Scholar 

  44. Kvetny J, Wilms L, Pedersen PL, Larsen J. Subclinical hypothyroidism affects mitochondrial function. Horm Metab Res. 2010.;42:324–327.

    Google Scholar 

  45. Siciliano G, Monzani F, Manca ML, et al. Human mitochondrial transcription factor A reduction and mitochondrial dysfunction in Hashimoto’s hypothyroid myopathy. Mol Med. 2002;8:326–333.

    PubMed  CAS  Google Scholar 

  46. Chicco AJ, Sparagna GC. Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol. 2007;292:C33–C44.

    Article  PubMed  CAS  Google Scholar 

  47. Carreras MC, Peralta JG, Converso DP, et al. Modulation of liver mitochondrial NOS is implicated in thyroid-dependent regulation of O(2) uptake. Am J Physiol Heart Circ Physiol. 2001;281:H2282–H2288.

    PubMed  CAS  Google Scholar 

  48. Skulachev VP. Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants. Q Rev Biophys. 1996;29:169–202.

    Article  PubMed  CAS  Google Scholar 

  49. Arrese M. Burning hepatic fat: therapeutic potential for liver-specific thyromimetics in the treatment of nonalcoholic fatty liver disease. Hepatology. 2009;49:348–351.

    Article  PubMed  Google Scholar 

  50. Musso G, Gambino R, Cassader M. Emerging molecular targets for the treatment of nonalcoholic fatty liver disease. Annu Rev Med. 2010;61:375–392.

    Article  PubMed  CAS  Google Scholar 

  51. Taylor AH, Stephan ZF, Steele RE, Wong NC. Beneficial effects of a novel thyromimetic on lipoprotein metabolism. Mol Pharmacol. 1997;52:542–547.

    PubMed  CAS  Google Scholar 

  52. Hassan MM, Kaseb A, Li D, et al. Association between hypothyroidism and hepatocellular carcinoma: a case-control study in the United States. Hepatology. 2009;49:1563–1570.

    Article  PubMed  Google Scholar 

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Acknowledgments

Claudia O. Zein was supported by Grant Number KL2 RR024990 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Mangesh R. Pagadala was supported by the grant number T32 DK061917 and DK 061732. Arthur J. McCullough was supported in part by NIH grant 5 U01 DK 061732.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH, USA

    Mangesh R. Pagadala & Srinivasan Dasarathy

  2. Department of Gastroenterology, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, 9500 Euclid Avenue, A30, Cleveland, OH, 44195, USA

    Claudia O. Zein & Arthur J. McCullough

  3. Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA

    Lisa M. Yerian

  4. Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA

    Rocio Lopez

  5. Department of Gastroenterology and Hepatology, 9500 Euclid Avenue, A30, Cleveland, OH, 44195, USA

    Arthur J. McCullough

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  1. Mangesh R. Pagadala
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  6. Arthur J. McCullough
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Correspondence to Arthur J. McCullough.

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Pagadala, M.R., Zein, C.O., Dasarathy, S. et al. Prevalence of Hypothyroidism in Nonalcoholic Fatty Liver Disease. Dig Dis Sci 57, 528–534 (2012). https://doi.org/10.1007/s10620-011-2006-2

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  • DOI: https://doi.org/10.1007/s10620-011-2006-2

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