Thyroid Dysfunction and Cholesterol Gallstone Disease

Irina Kube; Denise Zwanziger

doi:10.1055/a-1033-7273

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2020; 128(06/07): 455-461
DOI: 10.1055/a-1033-7273

Mini-Review

Thyroid Dysfunction and Cholesterol Gallstone Disease

Irina Kube

¹Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, Essen, Germany

,

Denise Zwanziger

¹Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, Essen, Germany

› Author Affiliations

Abstract

Cholesterol gallstone disease (CGD) affects 10–15% of the adult population worldwide and the prevalence increases as a result of longer life expectancy as well as rising obesity in the general population. Beside well established CGD risk factors including environmental and genetic determinants (LITH genes), a correlation between thyroid dysfunction and CGD has been suggested in several human and murine studies. Although the precise underlying mechanisms are poorly understood, thyroid hormones may impact bile flow, bile composition and the maintenance of the enterohepatic circulation. Further there is evidence that thyroid hormones possibly impact LITH genes which are regulated by nuclear receptors (NRs). A better understanding of the CGD pathomechanisms might contribute to personalized prevention and therapy of highly prevalent and economically significant digestive disease. This review presents the current knowledge about the association between CGD and thyroid hormone dysfunction.

Key words

bile - cholesterol gallstone disease - detoxification - enterohepatic circulation - lipid homeostasis - LITH genes - nuclear receptors - thyroid dysfunction - thyroid hormone

Full Text

References

References
1 Kratzer W, Mason RA, Kächele V. Prevalence of gallstones in sonographic surveys worldwide. J Clin Ultrasound 1999; 27: 1-7
2 Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut and Liver 2012; 6: 172-187
3 Inkinen J, Sand J, Nordback I. Association between common bile duct stones and treated hypothyroidism. Hepatogastroenterology 2000; 47: 919-921
4 Völzke H, Robinson DM, John U. Association between thyroid function and gallstone disease. World J Gastroenterol 2005; 11: 5530-5534
5 Cakir M, Kayacetin E, Toy H. et al. Gallbladder motor function in patients with different thyroid hormone status. Exp Clin Endocrinol Diabetes 2009; 117: 395-399
6 Laukkarinen J, Sand J, Nardback I. The underlying mechanisms: How hypothyroidism affects the formation of common bile duct stones- a review. HPB Surgery 2012; 2012: 102825
7 Wegrzyn-Bak M, Marczewski K, Maciejewski M. It is a link between gallstone disease and pathology of thyroid gland. ECE 2018;
8 Bauer M, Glenn T, Pilhatsch M. et al. Gender differences in thyroid system function: Relevance to bipolar disorder and its treatment. Bipolar Disorders 2014; 16: 58-71
9 Lammert F, Matern S. The genetic background of cholesterol gallstone formation: An inventory of human lithogenic genes. Curr Drug Targets Immune Endocr Metabol Disord 2005; 5: 163-170
10 Lammert F, Sauerbruch T. Mechanisms of disease: The genetic epidemiology of gallbladder stones. Nat Clin Prac. Gastroenterol Hepatol 2005; 2: 423-433
11 Khanuja B, Cheah YC, Hunt M. et al. Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice. Proc Natl Acad Sci USA 1995; 92: 7729-7733
12 Wang DQH, Zhang L, Wang HH. High cholesterol absorption efficiency and rapid biliary secretion of chylomicron remnant cholesterol enhance cholelithogenesis in gallstone-susceptible mice. Biochim Biophys Acta 2005; 1733: 90-99
13 Wang DQH, Paigen B, Carey MC. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: Physical-chemistry of gallbladder bile. J Lipid Res 1997; 38: 1395-1411
14 Joshi AD, Andersson C, Buch S. et al. Four susceptibility loci for gallstone disease identified in a meta-analysis of genome-wide association studies. Gastroenterology 2016; 151: 351-363
15 Ferkingstad E, Oddsson A, Gretarsdottir S. et al. Genome-wide association meta-analysis yields 20 loci associated with gallstone disease. Nature Com 2018; 9: 5101
16 Weber SN, Bopp C, Krawczyk M. et al. Genetics of gallstone disease revisited: Updated inventory of human lithogenic genes. Curr Opin Gastroenterol 2019; 35: 82-87
17 Wang Y, Yu X, Zhao QZ. et al. Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms. Zhejiang Univ-Sci B (Biomed & Biotechnol) 2016; 17: 515-525
18 Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone disease. Lancet 2006; 368: 230-239
19 Turley SD, Dietschy JM. The Metabolism and Excretion of Cholesterol by the Liver. New York: Raven Press; 1988: 617-641
20 Van Erpecum KJ, van Berge-Henegouwen GP. Gallstone: an intestinal disease?. Gut 1999; 44: 435-438
21 Carey MC. Critical tables for calculating the cholesterol saturation of native bile. J Lipid Res 1978; 19: 945-965
22 Rebholz C, Krawczyk M, Lammert F. Genetics of gallstone disease. Eur J Clin Invest 2018; 48: e12935
23 Scarabottolo L, Trezzi E, Roma P. et al. Experimental hypothyroidism modulates the expression of the low density lipoprotein receptor by the liver. Atherosclerosis 1986; 59: 329-333
24 Day R, Gebhard R, Schwartz HL. et al. Time course of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and messenger ribonucleic acid, biliary lipid secretion, and hepatic cholesterol content in methimazole-treated hypothyroid and hypophysectomized rats after triiodothyronine administration: Possible linkage of cholesterol synthesis to biliary secretion. Endocrinology 1989; 125: 459-468
25 Ellis ECS. Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes. World J Gastroenterol 2006; 12: 4640-4645
26 Hashimoto K, Cohen RN, Yamada M. et al. Cross-talk between thyroid hormone receptor and liver x receptor regulatory pathways is revealed in a thyroid hormone resistance mouse model. JBC 2006; 281: 295-302
27 Pedrelli M, Pramfalk C, Parini P. Thyroid hormones and thyroid hormone receptors: Effects of thyromimetics on reverse cholesterol transport. World J. Gastroenterol. 2010; 16: 5958-5964
28 Lammel Lindemann JA, Angajala A, Engler DA. et al. Thyroid hormone induction of human cholesterol 7 alpha-hydroxylase (Cyp7a1) in vitro. Mol Cell Endocrinol 2014; 388: 32-40
29 Christoffolete MA, Doleschall MEgri et al. Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway. J Endocrinol 2010; 205: 179–186
30 Kalaany NY, Gauthier KC, Zavacki AM. et al. LXRs regulate the balance between fat storage and oxidation. Cell Metabolism 2005; 1: 231-44.
31 Watanabe M, Sander MH, Mataki C. et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006; 439: 484-489
32 Van Erpecum KJ. Biliary lipids, water and cholesterol gallstones. Biol. Cell 2005; 97: 815-822
33 Bonde Y, Plösch T, Kuipers F. et al. Stimulation of murine biliary cholesterol secretion by thyroid hormone is dependent on a functional ABCG5/G8 complex. Hepatology 2012; 56: 1828-1837
34 Ahn HY, Lee KJ, Kim SH. et al. Effect of thyroid hormone to the expression of bile salt export pump. Endocrinol Metab. 2011; 26: 232-238
35 Gautherot J, Claudel T, Cuperus F. et al. Thyroid hormone receptor β1 stimulates ABCB4 to increase biliary phosphatidylcholine excretion in mice. J Lipid Res 2018; 59: 1610-1619
36 Laukkarinen J, Sand J, Saaristo R. et al. Is bile flow reduced in patients with hypothyroidism?. Surgery 2003; 133: 288-293
37 Laukkarinen J, Kööbi P, Kalliovalkama J. et al. Bile flow to the duodenum is reduced in hypothyreosis and enhanced in hyperthyreosis. Neurogastroenterology and Motility 2002; 14: 183-188
38 Inkinen J, Sand J, Arvola P. et al. Direct effect of thyroxine on pig sphincter of Oddi contractility. Dig Dis Sci 2001; 46: 182-186
39 Laukkarinen J, Sand J, Aittomäki S. et al. Mechanism of the prorelaxing effect of thyroxine on the sphincter of Oddi. Scand J Gastroenterol 2002; 37: 667-673
40 Van Erpecum KJ, Wang DQH, Moschetta A. et al. Gallbladder histopathology during gallstone formation: Relation to motility and concentrating function. J of Lipid Res 2006; 47: 32-41
41 Laurila JJ, Karttunen T, Koivukangas V. et al. Tight junction proteins in gallbladder epithelium: Different expression in acute acalculous and calculous cholecystitis. J of Histochemistry & Cytochemistry 2007; 55: 567-573
42 Tanaka H, Imasato M, Yamazaki Y. et al. Claudin-3 regulates bile canalicular paracellular barrier and cholesterol gallstone core formation in mice. J of Hepatol 2018; 69: 1308-1316
43 Costa LES, Clementino-Neto J, Mendes CB. et al. Evidence of aquaporin 4 regulation by thyroid hormone during mouse brain development and in cultured human glioblastoma multiforme cells. Front. Neurosci. 2019; 13: 317
44 Zwanziger D, Rakov H, Engels K. et al. Sex-dependent claudin-1 expression in the liver of euthyroid and hypothyroid mice. Eur Thyroid J 2015; 4: 67-73
45 Chiang JYL, Ferrell JM. Bile acid metabolism in liver pathobiology. Gene Expression 2018; 18: 71-87
46 Cuperus FJC, Claudel T, Gautherot J. et al. The role of canalicular ABC transporters in cholestasis. Drug Metab Dispos 2014; 42: 546-560
47 Attie AD, Kstelein JP, Hayden MR. Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis. J Lipid Res 2001; 42: 1717-1726
48 Cai JS, Chen JH. The mechanism of enterohepatic circulation in the formation of gallstone disease. J Membrane Biol 2014; 247: 1067-1082
49 Xiao L, Pan G. An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: The apical sodium-dependent bile acid transporter (SLC10A2/ASBT). Clin and Res in Hep and Gastroenterol. 2017; 41: 509-515
50 Gälman C, Bonde Y, Matasconi M. et al. Dramatically increased intestinal absorption of cholesterol following hypophysectomy is normalized by thyroid hormone. Gastroenterology 2008; 134: 1127-1136
51 Kahraman H, Kaya N, Demircali A. et al. Gastric emptying time in patients with primary hypothyroidism. Europ J of Gastroenterol and Hep 1997; 9: 901-904
52 Dubois A, Goldman JM. Gastric secretion and emptying in hypothyroidism. Dig Dis and Scie 1984; 29: 407-410
53 Tancevski I, Wehinger A, Demetz E. et al. Reduced plasma HDL in hyperthyroid mice coincides with decreased hepatic ABCA1 expression. Endocrinology 2008; 149: 3708-3712
54 Yoon JH, Choi HS, Jun DW. et al. ATP-binding cassette sterol transporters are differentially expressed in normal and diseased human gallbladder. Dig Dis and Scie 2013; 58: 431-439
55 Thompson JC, Vars HM. Biliary excretion of cholic acid and cholesterol in hyper-, hypo-, and euthyroid rats. Exp Biol and Med 1953; 83: 246-248
56 Katz AI, Emmanouel DS, Lindheimer MD. Thyroid hormone and the kidney. Nephrone 1975; 15: 3-5
57 Ghonem NS, Assis DN, Boyer JL. Fibrates and cholestasis. Hepatology 2015; 62: 635-643
58 John YL, Ferell CJM. Bile acid metabolism in liver pathobiology. Gene Expression 2018; 18: 71-87
59 Alnouti Y. Bile acid sulfation: a pathway of bile acid elimination and detoxification. Tox Sci 2009; 108: 225-246
60 Elekima OT, Mills CO, Ahmad A. et al. Reduced hepatic content of dehydroepiandrosterone sulphotransferase in chronic liver diseases. Liver 2000; 20: 45-50
61 Iqbal S, Vickers C, Elias E. Drug metabolism in end-stage liver disease. In vitro activities of some phase I and phase II enzymes. J Hepatol 1990; 11: 37-42
62 Loof L, Nyberg A. Bile salt sulphation in man. Liver bile salt sulphotransferase activity in patients with primary biliary cirrhosis. Ups J Med Sci 1983; 88: 1-8
63 Loof L, Wengle B. Enzymatic sulphation of bile salts in man. Bile salt sulphotransferase activity in percutaneous liver biopsy specimens from patients with liver disease. Scand J Gastroenterol 1982; 17: 69-76
64 Huang YH, Lee CY, Tai PJ. et al. Indirect regulation of human dehydroepiandrosterone sulfotransferase family 1A member 2 by thyroid hormones. Endocrinology 2006; 147: 2481-2489
65 Huang YH, Tsai MM, Lin KH. Thyroid hormone dependent regulation of target genes and their physiological significance. Chang Gung Med J 2008; 31: 325-334
66 Vázquez MC, Rigotti A, Zanlungo S. Molecular mechanisms underlying the link between nuclear receptor function and cholesterol gallstone formation. J of Lipids 2012; 547643
67 Schupp M, Lazar MA. Endogenous ligands for nuclear receptors: Digging deeper. J of Biol Chem 2012; 285: 40409-40415
68 Jiang ZY, Parini P, Eggersten G. et al. Increased expression of LXR alpha, ABCG5, ABCG8, and SR-BI in the liver from normolipidemic, nonobese Chinese gallstone patients. J Lipid Res 2008; 49: 464-472
69 Moghadamrad S, Montani M, Weimann R. et al. Cholelithiasis in a patient with gallstones and a normal gamma-glutamyl transferase. Hepatology 2013; 57: 2539-2541
70 Matsumoto K, Imasato M, Yamazaki Y. et al. Claudin 2 deficiency reduces bile flow and increases susceptibility to cholesterol gallstone disease in mice. Gastroenterol 2014; 147: 1134-1145
71 Lammert F, Wang DQH, Paigen B. et al. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: Integrated activities of hepatic lipid regulatory enzymes. JLR 1999; 40: 2080-2090
72 Chai J, Feng X, Zhang L. et al. Hepatic expression of detoxification enzymes is decreased in human obstructive cholestasis due to gallstone biliary obstruction. PLoS One 2015; 10: e0120055
73 Uppal H, Zhai Y, Gangopadhyay A. et al.. Activation of liver X receptor sensitizes mice to gallbladder cholesterol crystallization. Hepatology 2008; 47: 1331-1342
74 Moschetta A, Bookout AL, Mangelsdorf DJ. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. Nat Med 2004; 10: 1352-1358
75 Müller O, Schalla C, Scheibner J. et al. Expression of liver plasma membrane transporters in gallstone-susceptible and gallstone-resistant mice. Biochem J 2002; 361: 673-679
76 Renner O, Harsch S, Schaeffeler E. et al. A variant of the SLC10A2 gene encoding the apical sodium-dependent bile acid transporter is a risk factor for gallstone disease. PLoS One 2009; 4: e7321
77 Matsubara K, Nakamura N, Sanoh S. et al. Altered expression of the Olr59, Ethe1, and Slc10a2 genes in the liver of F344 rats by neonatal thyroid hormone disruption. J Appl Toxicol 2017; 37: 1030-1035