|Year : 2014 | Volume
| Issue : 3 | Page : 87-88
NAFLD, Prediabetes and Hypothyroidism: Fixing the Links
AG Unnikrishnan1, Shalbha Tiwari2, Vedavati Purandare1, Rita Basu3, Ananda Basu3
1 Department of Clinical Diabetology & Endocrinology, Chellaram Diabetes Institute, Maharashtra, India
2 Department of Diabetes and Endocrine Research, Chellaram Diabetes Institute, Pune, Maharashtra, India
3 Diabetes Research Centre, Division of Endocrinology, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA
|Date of Web Publication||13-Aug-2014|
A G Unnikrishnan
CEO, Chief Endocrinologist and Head of Research Division, Chellaram Diabetes Institute, 1st Floor, Lalani Quantum, Pune Bangalore Highway, Bavdhan Budruk, Pune 411 021, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Unnikrishnan A G, Tiwari S, Purandare V, Basu R, Basu A. NAFLD, Prediabetes and Hypothyroidism: Fixing the Links. Thyroid Res Pract 2014;11:87-8
|How to cite this URL:|
Unnikrishnan A G, Tiwari S, Purandare V, Basu R, Basu A. NAFLD, Prediabetes and Hypothyroidism: Fixing the Links. Thyroid Res Pract [serial online] 2014 [cited 2019 Dec 16];11:87-8. Available from: http://www.thetrp.net/text.asp?2014/11/3/87/138550
Today, non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function tests.  NAFLD is emerging as an important risk factor for chronic liver disease and cirrhosis. The clinical spectrum of NAFLD is varied; it may range from simple hepatic steatosis to steatosis with necro-inflammation and is often associated with fibrosis. There is a clear link between NAFLD and insulin resistant states such as obesity, type 2 diabetes and prediabetes.  Non-alcoholic fatty liver disease is often detected by a bright liver echo pattern on liver ultrasound. A liver biopsy provides an unquestionable diagnosis; however, given the risks of liver biopsy, it is rarely indicated for diagnosing or managing NAFLD in routine general practice.
Interestingly, NAFLD also seems to share a link with hypothyroidism. People with NAFLD have twice the prevalence of hypothyroidism when compared with people who have liver disease that is due to other etiologies. Animal studies have suggested that levothyroxine therapy can regress hepatic changes of NAFLD, and there have been anecdotal reports in humans too. , The association between hypothyroidism and hepatic fat is unexplained; though weight gain might play a role, obesity is often associated with NAFLD. However, obesity is not the only explanation, and nor is the explanation that hypothyroidism causes NAFLD by a direct effects on the liver an established one, despite the well-known associations between hypothyroidism and elevated liver enzymes.
Could insulin resistant states, such as obesity, type 2 diabetes or even prediabetes be a confounding factor in the diagnosis of NAFLD in hypothyroid subjects? It is well known that NAFLD is associated with all these three factors. What is not understood, however, is whether hypothyroidism is associated with components of the insulin-resistant syndrome, also referred to as the metabolic syndrome. This is in essence a cluster of problems like hyperglycemia, central obesity, hypertension, dyslipidemia and cardiovascular risk. It is well known that NAFLD is an emerging component of this syndrome. The relationship among the hypothyroidism, the metabolic syndrome and cardiovascular risk is less certain.  However, an Indian study has indicated that such an association exists. 
To answer the question above, a collaborative effort between the Universität zu Lübeck in Germany and the Christie Manchester Academic Health Science Centre in the United Kingdom attempted to summarize studies on thyroid hormone-dependent action on components of the metabolic syndrome.  The authors concluded that there was significant evidence to suggest that there is a clustering of metabolic syndrome components in persons with hypothyroidism- citing association between hypothyroidism and various components like hyperglycemia, hypertension, dyslipidemia and weight gain.
If the association between hypothyroidism and the metabolic syndrome were to be established in humans, more conclusive evidence could have accrued and indeed there is preliminary evidence to suggest the need for such a study. Lee et al., in a study of 7270 euthyroid subjects, showed that elevations of thyroid stimulating hormone (TSH - within the normal range) predicted the occurrence of metabolic syndrome components.  The American Health Aging and Body Composition study, done on over 3500 subjects again showed that there was a direct association between declining thyroid functions and the occurrence of the metabolic syndrome components except the waist circumference.  Since waist circumference, a component of the metabolic syndrome, is considered; this discordant result stresses that in future studies it may be better to focus on the association between hypothyroidism and the individual components of the metabolic syndrome, rather than the metabolic syndrome itself, as assessment of the latter may mask significant correlations between hypothyroidism and these components.
Given that hypothyroidism is associated with the components of the metabolic syndrome and also given that NAFLD is one such component what implications does this have for routine clinical practice? Well, for one, not only hypothyroidism and diabetes, many other endocrine diseases like growth hormone deficiency and Addison's disease are known to cluster with NAFLD. Some authors suggest that people with NAFLD need to be screened for endocrinopathies as well. Usually, the diagnostic work up of NAFLD involves testing for hepatitis B and C, autoantibodies, iron studies, serum ceruloplasmin, fasting glucose, lipid profile and liver ultrasonography. Testing for endocrine dysfunction is unlikely to be cost- effective. However, some persons with NAFLD, as suggested by results of a recent study from the Cleveland Clinic Foundation, may benefit from screening for hypothyroidism.  In this study, among subjects with NALFD, persons with the following characteristics were likely to have hypothyroidism; female gender, obesity and history of abstinence from alcohol. Hence, in this subgroup of persons with NAFLD, testing for thyroid dysfunction may be a more practical option. However, the practicability and cost effectiveness of such an approach requires further research, before it can be accepted as standard of care.
| References|| |
|1.||Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology 2004;40:1387-95. |
|2.||Ortiz-Lopez C, Lomonaco R, Orsak B, Finch J, Chang Z, Kochunov VG, et al. Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Diabetes Care 2012;35:873-8. |
|3.||Cable EE, Finn PD, Stebbins JW, Hou J, Ito BR, van Poelje PD, et al. Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonist. Hepatology 2009;49:407-17. |
|4.||Gardner CJ, Richardson P, Wong C, Polavarapu N, Kemp GJ, Cuthbertson DJ. Hypothyroidism in a patient with non-alcoholic fatty liver disease. BMJ 2011;342:c7199. |
|5.||Raza SA, Mahmood N. Subclinical hypothyroidism: Controversies to consensus. Indian J Endocrinol Metab 2013;17:S636-42. |
|6.||Misra S, Singh B. Insulin resistance and hypothyroidism: A complex relationship in non-alcoholic fatty liver disease. J Indian Med Assoc 2013;111:324-6, 329. |
|7.||Iwen KA, Schröder E, Brabant G. Thyroid hormones and the metabolic syndrome. Eur Thyroid J 2013;2:83-92. |
|8.||Lee YK, Kim JE, Oh HJ, Park KS, Kim SK, Park SW, et al. Serum TSH level in healthy Koreans and the association of TSH with serum lipid concentration and metabolic syndrome. Korean J Intern Med 2011;26:432-9. |
|9.||Park SB, Choi HC, Joo NS. The relation of thyroid function to components of the metabolic syndrome in Korean men and women. J Korean Med Sci 2011;26:540-5. |
|10.||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. |