The Risk of Developing Non-Alcoholic Fatty Liver Disease in Adult Patients with Subclinical Hypothyroidism Compared to Euthyroid: An Evidence-based Case Report

Kemas Rakhmat Notariza, Wismandari Wisnu


Background: hypothyroidism is a common concomitant disease of non-alcoholic fatty liver disease (NAFLD). Previous studies regarding the relationship between subclinical hypothyroidism and NAFLD showed conflicting results, ranging from a strong association to not significant one. This case report aimed to investigate the risk of developing NAFLD in subclinical hypothyroidism patients. Methods: literature searching used ScienceDirect, PubMed, ProQuest, and Scopus. Filtering process of titles and abstracts by using inclusion and exclusion criteria yielded 4 eligible articles (1 systematic review, 1 prospective cohort, 1 retrospective cohort, and 1 case-control study) for answering the clinical question. Critical appraisal was conducted by using worksheets from Centre for Evidence-Based Medicine, University of Oxford. Results: the systematic review was considered invalid due to its less comprehensive search for relevant studies, inappropriate article selection to find a causal relationship between diseases, and statistical heterogeneity. The retrospective cohort was decided unimportant because it possessed a relative risk of 0.85 (95% confidence interval [CI], 0.72--1.00) which the upper limit of its CI included 1.00. The rest were valid and had important risk relative and odds ratio (1.27 [95% CI, 1.09--1.47], 3.41 [95% CI, 1.16--9.98]; respectively). The number needed to harm (5—17) indicated the clinically meaningful harm of the exposure since only a few patients with subclinical hypothyroidism is needed to obtain one additional NAFLD incidence. Those two articles were also suitable to be applied in our case. Conclusion: patients with subclinical hypothyroidism, compared to euthyroid patients, are at higher risk of developing NAFLD.


euthyroid; non-alcoholic fatty liver disease; subclinical hypothyroidism


Peeters RP. Subclinical hypothyroidism. N Engl J Med. 2017;376:2556–65.

Canaris GJ, Manowitz NR, Mayor G, Ridgway C. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:526–34.

Nair SN, Kumar H, Raveendran M, Menon VU. Subclinical hypothyroidism and cardiac risk: lessons from a South Indian Population Study. Indian J Endocrinol Metab. 2018;22:217–22.

Pusat Data dan Informasi Kementerian Kesehatan RI. Situasi dan analisis penyakit tiroid. 1st ed. Jakarta: Kementerian Kesehatan RI; 2015. p. 1-8.

Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11–20.

Mavrogiannaki AN, Migdalis IN. Nonalcoholic fatty liver disease, diabetes mellitus and cardiovascular disease: Newer data. Int J Endocrinol. 2013;2013:1–8.

Chen SH, He F, Zhou HL, Wu HR, Xia C, Li YM. Relationship between nonalcoholic fatty liver disease and metabolic syndrome. J Dig Dis. 2011;12:125–30.

Erdogan M, Canataroglu A, Ganidagli S, Kulaksızoglu M. Metabolic syndrome prevalence in subclinic and overt hypothyroid patients and the relation among metabolic syndrome parameters. J Endocrinol Invest. 2011;34:488–92.

Mazo DF de C, Lima VMR de, Stefano JT, Rabelo F, Faintuch J, Oliveira CP de. Gluco-lipidic indices in treated hypothyroidism associated with nonalcoholic fatty liver disease. Arq Gastroenterol. 2011;48:186–9.

Pagadala MR, Zein CO, Dasarathy S, Yerian LM, Lopez R, McCullough AJ. Prevalence of hypothyroidism in nonalcoholic fatty liver disease. Dig Dis Sci. 2012;57:528–34.

Xu C, Xu L, Yu C, Miao M, Li Y. Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly Chinese. Clin Endocrinol (Oxf). 2011;75:240–6.

Chung GE, Kim D, Kim W, et al. Non-alcoholic fatty liver disease across the spectrum of hypothyroidism. J Hepatol. 2012;57:150–6.

Eshraghian A, Dabbaghmanesh MH, Eshraghian H, Fattahi MR, Omrani GR. Nonalcoholic fatty liver disease in a cluster of Iranian population: thyroid status and metabolic risk factors. Arch Iran Med. 2013;16:584–9.

Straus SE, Glazziou P, Richardson WS, Haynes RB. Evidence-based medicine: how to practice and teach it. 4th ed. Toronto: Churchill Livingstone; 2011. p. 98-108, 183-203.

He W, An X, Li L, et al. Relationship between hypothyroidism and non-alcoholic fatty liver disease: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2017;8:335–46.

Bano A, Chaker L, Plompen EPC, et al. Thyroid function and the risk of nonalcoholic fatty liver disease: the Rotterdam Study. J Clin Endocrinol Metab. 2016;101:3204–11.

Lee KW, Bang KB, Rhee EJ, Kwon HJ, Lee MY, Cho YK. Impact of hypothyroidism on the development of non-alcoholic fatty liver disease: A 4-year retrospective cohort study. Clin Mol Hepatol. 2015;21:372.

Parikh P, Phadke A, Sawant P. Prevalence of hypothyroidism in nonalcoholic fatty liver disease in patients attending a tertiary hospital in western India. Indian J Gastroenterol. 2015;34(2):169–73.

Xu L, Ma H, Miao M, Li Y. Impact of subclinical hypothyroidism on the development of non-alcoholic fatty liver disease: A prospective case-control study. J Hepatol. 2012;57:1153–4.

Kim D, Kim W, Joo SK, Bae JM, Kim JH, Ahmed A. Subclinical hypothyroidism and low-normal thyroid function are associated with nonalcoholic steatohepatitis and fibrosis. Clin Gastroenterol Hepatol. 2018;16:123–131.e1.

Vyakaranam S, Vanaparthy S, Nori S, Palarapu S, Bhongir AV. Study of insulin resistance in subclinical hypothyroidism. Int J Heal Sci Res. 2014;4:147–53.

Bugianesi E, Moscatiello S, Ciaravella MF, Marchesini G. Insulin resistance in nonalcoholic fatty liver disease 75. Curr Pharm Des. 2010;16:1941–51.

Tian L, Song Y, Xing M, et al. A novel role for thyroid-stimulating hormone: up-regulation of hepatic 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase expression through the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-responsive element binding protei. Hepatology. 2010;52:1401–9.

Santi A, Duarte MMMF, De Menezes CC, Loro VL. Association of lipids with oxidative stress biomarkers in subclinical hypothyroidism. Int J Endocrinol. 2012;2012:1–7.

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