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ORIGINAL ARTICLE
Year : 2012  |  Volume : 9  |  Issue : 3  |  Page : 84-87

Implication of altered thyroid state on liver function


Department of Physiology, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria

Date of Web Publication11-Aug-2012

Correspondence Address:
Roland E Akhigbe
Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-0354.99649

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  Abstract 

Objective: The thyroid gland is essential for metabolism and normal function of body cells, including the liver cells. It helps in the development and maturation of the hepatocytes and other body cells and tissues. This study investigated the effect of altered thyroid state on liver function. Materials and Methods: Rats were randomized into three groups: control, hypothyroid, and hyperthyroid rats. Results: Thyroid dysfunction led to lysis of the hepatocytes. Hypothyroidism caused significant (P < 0.05) reduction of body weight gain, serum total protein, albumin, direct bilirubin, transaminases, and gamma glutamyl transferase. Hyperthyroidism led to significant (P < 0.05) body weight loss. Hypothyroidism and hyperthyroidism were associated with significant (P < 0.05) increase in liver weight and diameter. Conclusion: This study reveals that although hyperthyroid state is not associated with altered liver function, hypothyroidism caused hepatic dysfunction. We therefore suggest that liver function indices should be monitored in altered thyroid states, especially in hypothyroidism.

Keywords: Hyperthyroid, hypothyroid, liver enzymes, protein, weight


How to cite this article:
Ajayi AF, Akhigbe RE. Implication of altered thyroid state on liver function. Thyroid Res Pract 2012;9:84-7

How to cite this URL:
Ajayi AF, Akhigbe RE. Implication of altered thyroid state on liver function. Thyroid Res Pract [serial online] 2012 [cited 2017 Mar 22];9:84-7. Available from: http://www.thetrp.net/text.asp?2012/9/3/84/99649


  Introduction Top


The thyroid gland is an endocrine structure that synthesizes and releases triiodothyronine (T 3 ) and thyroxine (T 4 ). [1] These hormones are the only iodine-containing amine hormones in the vertebrate [1] and are necessary for optimal growth, development, and function of tissues. [2] They have vital influence on oxygen consumption and metabolic rate of all cells including hepatocytes, [2],[3] thus alter hepatic function. The liver in turn metabolizes thyroid hormones through conjugation, excretion, peripheral deiodination, and in the synthesis of thyroid-binding globulin, and thus controls their endocrine effects. [4],[5],[6],[7],[8] Hence, normal circulating levels of thyroid hormones are required for healthy hepatic function, [9] suggesting that altered thyroid function may cause hepatic dysfunction and vice versa. [4]

Studies have reported conflicting results on the effect of hepatic dysfunction seen in liver diseases on thyroid function. Shimanda

et al[10] documented that chronic liver disease is associated with low circulating T 4 and its conversion to T 3 . Soylu et al, [11] however, reported hyperthyroidism in intrahepatic cholestatic patients. Interestingly, Borzio et al[12] observed that although most patients with chronic liver disease have low T 3 , T 4 is maintained within normal range. The discrepancy seen in these studies has been reported to be dependent on the different analytical methods used and patients investigated. [12]

Although few studies have documented the pathophysiological effect of hypothyroidism, including its effect on liver function, none has reported the comparison of the effect of hypothyroidism and hyperthyroidism on hepatic function. This seems to be the first study to report the effect of thyroid dysfunction (hypothyroid and hyperthyroid) on hepatic function in experimental model.


  Materials and Methods Top


Animals

Sprague-Dawley rats of comparable weight (185.3 ± 4.5) were obtained from the Animal Holding Unit of the Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria. The animals were kept in wire mesh cages and were acclimatized to laboratory condition (12 day: 12 light cycle). They were allowed unrestricted access to rat pellet and water.

Treatments

Rats were randomly allocated into three groups (n = 6): control, hypothyroid, and hyperthyroid. Hypothyroidism was induced by administration of 5 mg/250 g body weight of carbimazole, while hyperthyroidism was induced by administration of 5 μg/100 g body weight of levothyroxine. Treatments lasted for 35 days. Experimental study was in accordance with the Institution's guidelines and that of the European convention for the protection of vertebrate animals and other scientific purposes-ETS-123. [13]

Determination of body weight change, liver morphometry, and thyroid and liver functions

The weights of rats were recorded weekly, [14] and at the end of the experiment, the percentage weight change was determined as the ratio of weight change to initial weight multiplied by 100.

At the end of the experiment, blood samples were collected by cardiac puncture, serum was obtained, and biochemical parameters were assayed. The liver of rats were excised, blotted with tissue paper, and thereafter weighed. The liver diameter of each rat was also measured.

Thyroid and liver function tests were assayed using standard assay kit. [3],[15],[16]

Histopathological studies were done as previously described. [16]

Statistical analysis

Data were analyzed using one-way analysis of variance complemented with unpaired t-test. Duncan Multiple Range Test and Turkey's Multiple Comparison Test were used as post hoc tests. Data are expressed as mean ± standard deviation.


  Results Top


Carbimazole led to significant (P < 0.05) decrease in serum T 3 and T 4 when compared with the control and levothyroxine-treated rats. It also caused a significant (P < 0.05) rise in serum thyroid-stimulating hormone (TSH). On the other hand, levothyroxine caused a significant (P < 0.05) increase in serum T 3 and T 4, and a significant (P < 0.05) decrease in serum TSH when compared with the control [Table 1].
Table 1: Effect of altered thyroid state on TSH, T3, and T4

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Carbimazole and levothyroxine treatments led to significant (P < 0.05) reduction in body weight gain in comparison with the control. Rats treated with carbimazole showed weight gain, but this was significantly (P < 0.05) reduced compared with that seen in the control; however, levothyroxine caused significant (P < 0.05) body weight loss. Nevertheless, carbimazole and levothyroxine caused significant (P < 0.05) increase in liver weight and diameter, although levothyroxine caused a more significant increase [Figure 1] and [Figure 2].
Figure 1: Effect of altered thyroid state on body weight change

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Figure 2: Effect of altered thyroid state on liver morphometry

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Serum globulin, total bilirubin, and alanine phosphatase were comparable (P > 0.05) in all groups. Serum total protein, albumin, aspartate amino transaminase, alanine aminotransaminase, and gamma glutamyl transferase were only comparable (P > 0.05) between the control and levothyroxine-treated, but showed significant (P < 0.05) reduction in carbimazole-treated rats. Carbimazole also caused significant (P < 0.05) decrease in direct bilirubin when compared with other groups [Table 2] [Figure 3] and [Figure 4].
Figure 3: Effect of altered thyroid state on serum total protein, albumin and globulin

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Figure 4: Effect of altered thyroid state on serum total and direct bilirubin hormones

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Table 2: Effect of altered thyroid state on serum concentrations of liver enzymes

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Histomorphological studies showed that carbimazole and levothyroxine caused lysis of hepatocytes which was more prominent in carbimazole-treated rats [Figure 5].
Figure 5: Effect of thyroid dysfunction on liver histomorphology (a) Control, (b) Carbimazole-treated, (c) Levothyroxine-treated

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  Discussion Top


Thyroid hormones modulate the functions of body cells, tissues, and organs. They play essential roles in growth, differentiation, maturation, and metabolism. [17] Interaction between thyroid hormones and liver function was reported earlier. [3],[10],[11],[12] The role of hypothyroidism on liver dysfunction has been documented; [3] however, the effect of hypothyroid and hyperthyroid states on hepatic function needs to be studied. This study documents the effect of experimental hypothyroidism and hyperthyroidism on hepatic function in animal model. Treatment with carbimazole and levothyroxine led to hypothyroid and hyperthyroid states, respectively. This was confirmed by thyroid function test. TSH, T 3 , and T 4 were significantly different in all groups. Carbimazole caused significant fall in thyroid hormones and a significant rise in TSH when compared with the control, confirming hypothyroid state. Levothyroxine led to significant rise in thyroid hormones and a significant decrease in TSH when compared with the control, confirming hyperthyroid state. The reduction in thyroid hormones and a rise in TSH seen in carbimazole treatment and the rise in thyroid hormones and fall in TSH observed in levothyroxine treatment are due to the negative feedback mechanism along the hypothalamic-pituitary-thyroid axis. [18]

This study shows that there was a significant reduction in body weight gain in carbimazole-induced hypothyroid rats. This is consistent with previous studies that reported reduction in weight gain in propylthiouracil-induced hypothyroidism and neonatal hypothyroidism. [19] This explains the fact that normal concentrations of thyroid hormones are required for optimal growth and development. Levothyroxine-induced hyperthyroidism led to significant weight loss. This confirms the well-documented effect of hyperthyroidism on body weight. [18] However, thyroid dysfunction caused significant increase in liver weight and diameter. This seems to be the first study to document the effect of thyroid dysfunction on liver morphometry.

Liver function test is important in determining the functional state of the organ and assessing the hepatotoxic potentials of exogenous compounds. The liver performs myriad of metabolic functions, thus accounting for the greatest percentage of metabolism of food, drug, and foreign substances. Hepatic dysfunction is characterized by alterations in serum levels of liver enzymes and metabolic products. Hepatic damage is usually observed as a rise in serum alanine transaminase (ALT), aspartate aminotransaminase (AST), and alanine phosphatase (ALP).

This study also seems to be the first to report the effect of hyperthyroidism in comparison with hypothyroidism on hepatic function. Liver function test was comparable between the control and hyperthyroid rats, thus suggesting that hyperthyroidism is not associated with alteration of liver function. However, total protein, albumin, direct bilirubin, transaminases, and gamma glutamyl transferase were reduced in hypothyroid rats. These results are in accord with previous study that reported insignificant decrease in ALT and albumin, although total bilirubin, total protein, AST, and ALP were insignificantly higher in hypothyroid patients when compared with euthyroid patients. [3] The lack of significance in a previous study was due to cases of subclinical hypothyroidism used in the study. [3] The significant reductions of transaminases and gamma glutamyl transferase seen in hypothyroid rats in this study imply that hypothyroidism is not a predisposing factor to loss of functional integrity of the hepatic cell membranes and cellular leakage of liver enzymes. It may also infer that hypothyroidism led to reduced liver enzyme activity.

Histomorphological study revealed lysis of hepatic cells in hypothyroid and hyperthyroid rats. The destructive disruption was more pronounced in hypothyroidism. This observation could suggest that the lysis seen in hyperthyroid rats was not significant enough to modulate liver function indices, while the prominent cell disruption in hypothyroid rats plays a role in the hypothyroid-induced liver dysfunction observed.

The novelty of this study bridges the gap in the dearth of knowledge in the open literature on the effect of hypothyroidism and hyperthyroidism on liver function. The results from this study revealed that although hyperthyroid state is not associated with altered liver function, hypothyroidism caused hepatic dysfunction. However, both states of thyroid dysfunction showed altered liver architecture on histologic examination. It is thus recommended that liver function should be monitored in conditions associated with thyroid dysfunction to avoid hepatic complications of thyroid dysfunction.

 
  References Top

1.Boelaert K, Franklyn. JA. Thyroid hormone in health and disease. J Endocrinol 2005;187:1-15.  Back to cited text no. 1
    
2.Yen PM. Physiology and molecular basis of thyroid hormone action. Physiol Rev 2001;81:1097-142.  Back to cited text no. 2
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3.Arora S, Chawla R, Tayal D, Gupta VK, Sohi JS, Mallika V. Biochemical markers of liver and kidney function are influenced by thyroid function-a case-controlled follow up study in Indian hypothyroid subjects. Ind J Clin Biochem 2009;24:370-4 .  Back to cited text no. 3
    
4.Malik R, Hodgson H. The relationship between the thyroid gland and the liver. Q J Med 2002;95:559-69.  Back to cited text no. 4
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5.Chopra IJ, Solomon DH, Chopra U, Young RT, Chuateco GN. Alterations in circulating thyroid hormones in hepatic cirrhosis; evidence for euthyroidism despite subnormal serum triiodothyronine. J Clin Endocrinol Metab 1974;39:501-11.  Back to cited text no. 5
    
6.Nomura S, Pittman CS, Chambers JB, Buck MW, Shimizu T. Reduced peripheral conversion of thyroxine to triiodothyronine in patients with hepatic cirrhosis. J Clin Invest 1975;56:643-52.  Back to cited text no. 6
    
7.Green JRB, Snitcher EJ, Mowat NA, Ekins RP, Rees LH, Dawson AM. Thyroid function and thyroid regulation in euthyroid men with chronic liver disease: Evidence of multiple abnormalities. Clin Endocrinol (Oxf) 1977;7:453-61.  Back to cited text no. 7
    
8.Walfish PG, Orrego H, Israel Y, Blake, J Kalant H. Serum triiodothyronine and other clinical and laboratory indices of alcoholic liver disease. Ann Intern Med 1979;91:13-6.  Back to cited text no. 8
    
9.Youssef WI, Mullen KD. The liver in other (nondiabetic) endocrine disorders. Clin Liver Dis 2002;6:879-89.  Back to cited text no. 9
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10.Shimada T, Higashi K, Umeda T, Sato T. Thyroid functions in patients with various chronic liver diseases. Endocrinol Jpn 1988;35:357-69.  Back to cited text no. 10
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11.Soylu A, Taskale MG, Ciltas A, Kalayci M, Kumbasar AB. Intrahepatic cholestasis in subclinical and overt hyperthyroidism: two case reports. J Med Case Rep 2008;2:116.  Back to cited text no. 11
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12.Borzio M, Caldara R, Borzio F, Piepoli V, Rampini P, Ferrari C. Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism. Gut 1983;24:631-6.  Back to cited text no. 12
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13.European Convention for the protection of vertebrate animals used for experimental and other scientific purposes. European Treaty Series, Strasbourg, ETS-123, 2005.  Back to cited text no. 13
    
14.Akhigbe RE, Olatunji LA, Soladoye AO, Oyeyipo IP. Effect of angiotensin 1-converting enzyme inhibitor, captopril, on body weight, and food and water consumption in oral contraceptive-treated rats. Am J Biochem Mol Biol 2011;1:95-100.  Back to cited text no. 14
    
15.Akhigbe RE, Azeez OM, Ige SF, Oyeyipo IP, Ajao FO, Soladoye AO. Hemorheological effect of long-term administration of oral contraceptive in rats. Int J Pharmacol 2008;4:403-6.  Back to cited text no. 15
    
16.Ige SF, Akhigbe RE, Edeogho O, Ajao FO, Owolabi OQ, Oyekunle OS, et al. Hepatoprotective activities of Allium cepa in cadmium-treated rats. Int J Pharm Pharm Sci 2011; In press.  Back to cited text no. 16
    
17.Christian MS, Trenton NA. Evaluation of thyroid function in neonatal and adult rats: The neglected endocrine mode of action. Pure Appl Chem 2003;75:2055-68.  Back to cited text no. 17
    
18.Guyton AC, Hall JE. Thyroid metabolic hormones: In: Textbook of Medical Physiology. 11 th ed. Philadelphia, PA: Saunders Elsevier 2006. p. 931-43.  Back to cited text no. 18
    
19.Maran RR, Sivakumar R, Arunakaran J. Duration-dependent effect of transient neonatal hypothyroidism on Sertoli and germ cell number, and plasma and testicular interstitial fluid androgen binding protein concentration. Endocr Res 1999;25:323-40.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]


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