Influence of hypothyroidism on biochemical markers of liver function test: a cross sectional study

Introduction: Normal level of thyroid hormone is important for normal hepatic function as it maintain the metabolism of bilirubin by playing a role in the enzymatic activity of glucuronyltransferase and by regulating the level of ligandin. The liver in turn glucuronidates and sulphates the thyroid hormone, excretes into bile and regulates their systemic endocrine effects. Therefore hepatic dysfunction is commonly observed in patients with thyroid disease. Aim was to determine the biochemical markers of Liver Function Test (LFT) in patients with hypothyroidism and their possible correlation with thyroid profile. Methods: Thyroid profile and liver function test (LFT) were evaluated in 40 patients with subclinical hypothyroidism (TSH 6.0-9.9mIU/L), 40 patients with overt hypothyroidism (TSH ≥10.0 mIU/L) between 20-50 years of age and were compared with 40 age matched normal euthyroid controls after applying exclusion criteria. Thyroid profile and LFT were estimated using fully autoanalyser VITROS 5600 considering p value <0.05 as significant. Results and observations: Subjects with both subclinical hypothyroidism and overt hypothyroidism had significantly raised serum AST, ALT, ALP (P<0.0001) and total protein levels (P<0.01) compared to controls. Further, TSH showed significant positive correlation with AST, ALT and ALP (P<0.05) in both subclinical and overt hypothyroidism whereas FT3 and FT4 had a significant negative correlation with AST, ALT and ALP (P<0.05) in overt hypothyroidism. Conclusion: It might be necessary to monitor liver enzymes frequently in hypothyroid patients as declining liver function may be missed by single assessment and deranged biochemical parameters of LFT might indicate underlying altered thyroid status. Key wordsLFT, FT3, FT4, TSH Introduction: The thyroid gland synthesizes and releases triiodothyronine (T3) and thyroxine (T4), which represent the only iodine containing hormones in the vertebrates. T3 is the biologically active thyroid hormone (1) .The major secretory product of the thyroid is a prohormone (T4), which is activated in peripheral tissues by outer ring deiodination to T3. There are three homologous iodothyronine deiodinases which catalyses these reactions (2),(3) . Type I deiodinase is located in liver, kidney, and thyroid. In addition to that, the liver has an important role in thyroid hormone transport and metabolism. These hormones are required for the normal growth, development and function of nearly all tissues, with major effects on oxygen consumption and metabolic rate (4) . Thyroid hormone synthesis and secretion is regulated by a negative feedback system that involves the hypothalamus, pituitary, and the thyroid gland (5) . Indian Journal of Basic and Applied Medical Research; March 2016: Vol.-5, Issue2, P.478-490 479 www.ijbamr.com P ISSN: 2250-284X , E ISSN : 2250-2858 The free, unbound component of thyroid hormone within plasma is in equilibrium with the proteinbound hormone and accounts for it’s biological activities. Though tissues are exposed to the same plasma concentrations of free T4 and T3 free hormone, their concentrations in different tissues vary according to the transport and deiodinase activity within specific tissues (6) . Thyroid hormones regulate the basal metabolic rate of all cells including hepatocytes. The liver in turn metabolizes the thyroid hormones and regulates their systemic endocrine effects (7) . Thyroid hormones are glucuronidated and sulphated within the liver and subsequently excreted into bile; in addition, these hormones maintain the metabolism of bilirubin by playing a role in the enzymatic activity of glucuronyltransferase and by regulating the level of ligandin, a major organic anion-binding protein (8) .In fact, there are several clinical and laboratory associations between thyroid and liver diseases namely(i) Liver damage secondary to the systemic effect of thyroid hormone excess or direct toxic effects and subclinical physiological effects of thyroid hormone on liver functions. (ii) Some patients with chronic liver diseases may have thyroiditis, hyperthyroidism or hypothyroidism through autoimmune mechanisms. (iii) Alterations of thyroid hormone metabolism or tests secondary to liver disease, and (iv) Liver or thyroid disorders related to the therapy of thyroid or liver disease. Therefore, it is not surprising that hepatic dysfunction is commonly observed in patients with thyroid disease. Thus, the interpretation of thyroid function tests in patients with liver disease as well as the interpretation of liver bio-chemical tests in patients with thyroid disease must take these facts into account if errors in patients care are to be avoided . The thyroid frequently is a common target of disease or dysfunction (13) .Thyroid disorders are commonly separated into two major categories, hyperthyroidism (caused by an overactive thyroid gland) and hypothyroidism (due to a poorly functioning thyroid gland), depending on whether serum thyroid hormone levels (T4 and T3) are increased or decreased, respectively. Both hypothyroidism and hyperthyroidism have potentially fatal systemic manifestations (14) . Thyroid hormones are essential for normal organ growth, development, function and regulation of the basal metabolic rate of all cells and therefore, its alteration can affects the entire metabolism (15) . Most affected organs include liver and heart. So, it alters the liver enzymes like ALP, AST, ALT, GGT and cardiac enzymes like CPK, LDH and AST (16, 17, 18) . ALT may also be elevated occasionally and cholesterol elevation is as a rule due to hypometabolism. The later may result in fatty liver causing mild but prolonged AST and/or ALT elevation, and therefore, be erroneously considered chronic hepatitis, particularly before the advent of hepatitis C virus asseys. These biochemical changes, usually mild, are also reversible with adequate thyroid replacement therapy. There is also evidence that hypothyroidism may directly affect the liver structure or function. Hypothyroidism has been associated in a few case reports with cholestatic jaundice attributed to reduced bilirubin and bile excretion. In experimental hypothyroidism, the activity of bilirubin UDP-glucuronyltransferase is decreased, resulting in a reduction in bilirubin excretion (20) . The reduction in bile flow may be in part due to an increase in membrane cholesterol-phospholipid ratio and diminished membrane fluidity (20) which may affect a number of canalicular membrane Indian Journal of Basic and Applied Medical Research; March 2016: Vol.-5, Issue2, P.478-490 480 www.ijbamr.com P ISSN: 2250-284X , E ISSN : 2250-2858 transporters and enzymes, including the Na + -K + ATPase. The triad of reduced bilirubin excretion, hypercholesterolaemia and hypotonia of the gall bladder seen in hypothyroidism increases the incidence of gallstones (21) . Recent studies have shown that the hepatic abnormalities associated with hypothyroidism can be reversible over a matter of weeks with thyroxine replacement, with no residual liver damage (22,23) . So, it is evident that thyroid dysfunction may affect liver function and liver disease modulates thyroid hormone metabolism, and a variety of systemic diseases affect both organs. Aims and objectives: Present study was done to evaluate the biochemical parameters of thyroid function test (FT3, FT4, TSH) and liver function test among known hypothyroid patient and healthy control as well as to find any possible correlation among the measured parameters under study. Materials and methods: An analytical cross-sectional study was conducted on subjects of age group between 20-50 yrs attending out patient department (OPD) of Gauhati Medical College & Hospital after taking approval from institutional ethics committee. Total no of 40 patients with diagnosed subclinical hypothyroidism and 40 patients with diagnosed overt hypothyroidism each, coming for thyroid function test were enrolled in the study and compared with 40 age matched normal euthyroid controls. Informed consent duly signed by each of the participants was taken. Thyroid profile tests (FT3, FT4 and TSH) were estimated to categorize subclinical hypothyroidism and overt hypothyroidism. Subjects were divided into two groups, test group1 and test group 2. 1) Test group 1consists of 40 patients with subclinical hypothyroidism (TSH 6.0-9.9