Serum paraoxonase-1 activity as a novel marker in the diagnosis and prognosis of hyperthyroidism
About this article
Abstract
Thyrotoxicosis or hyperthyroidism is the clinical syndrome caused by an excess of circulating free thyroxine and free triiodothyronine, or both. It was first diagnosed in 1979 in the US. Since this time, the frequency of this diagnosis has increased. It is common, affecting about 2% of women and 0.2% of men. The most common causes of Thyrotoxicosis are Graves' disease and formation of multinodular goiter and autonomously functioning solitary thyroid nodule. In excessive production of thyroid hormones, the basal metabolic rate can be increased by 100%. Hyperthyroidism also induces a hyperdynamic cardiovascular state that is associated with tachycardia, systolic hypertension, atrial fibrillation and increased cardiovascular mortality. The present study was designed to investigate the relationship among the serum PON-1 activity, lipid profile, and thyroid hormone level in patients with hyperthyroidism. In our research, we have estimated PON 1 activity in hyperthyroidism. We found the PON 1 activity decreased in the hyperthyroid patients (144.89 ± 3.27 U/ml) as compared to controls (214.71 ± 5.46 U/ml) significantly (p < 0.05). The thyroid hormones T3 and T4 also significantly increases (p < 0.001) in hyperthyroidism. In case of lipid profile triacylglycerol, HDL cholesterol, LDL cholesterol as well as VLDL cholesterol was also found significantly decreased (p < 0.05) in hyperthyroidism. In our study, we found a decrease in triacylglycerol, HDL cholesterol, LDL cholesterol as well as VLDL cholesterol. However, the decrease in HDL, LDL and VLDL cholesterol may also be associated with other disorders. Further, the blood quantity required for lipid profile is large (5 ml) and patients have to be fast for at least 14 hours. Similarly, estimation of lipid profile is time consuming method and hence it is not preferable as a marker.
The increase in thyroid hormones T3 and T4 significantly correlates with hyperthyroidism. However, estimation of thyroid hormone also required large (5 ml) quantity of blood sample. Similarly, the sample required should be always fresh. The estimation is carried generally by enzyme linked immune sorbent assay (ELISA) which is time consuming and costly method. But, on the other hand quantity of blood sample required for estimation of PON 1 activity is very less (1 ml). The estimation of PON 1 activity is easy and the method is chief. The most important thing is that PON 1 activity is decreased only in few disorders. Further, it correlates well with severity of hyperthyroidism. Thus, PON 1 activity is a novel marker in the diagnosis and prognosis of hyperthyroidism.
References
[1] Kale M.K., Bhusari K.P. and Umathe S.N., Role of thyroid hormones in the generation of widespread oxidative stress, J Cell Tissue Res 2007; 7 (1): 871-6.
[2] Slater M. R., Komkov A., Robinson L. E.,Hightower D. Long-term follow-up of hyperthyroid cats treated with iodine131.Veterinary Radiology and Ultrasound 1994; 35:204-9.
[3] Nicholas A, Nicki R, Brian R. Davidson's Principles & Practice of Medicine. 20th ed.Edinburgh: Churchill Livingstone, 2006: 746-749.
[4] Desai SP. Clinician's Guide to Laboratory Medinice. 3rd ed. Cleveland: Lexicomp , 2004: 371.
[5] Gago-Dominguez, Castelao J. Role of lipid peroxidation and oxidative stress in the association between thyroid diseases and breast cancer. Crit Rev Oncol Hematol 2008; 68: 107–14.
View more references (30)
[6] Fazio S, Palmieri E, Lombardi G. Effects of thyroid hormone on the cardiovascular system. Recent Prog Horm Res 2004; 59: 31–50.
[7] Zhu X and Cheng SY. New insights into regulation of lipid metabolism by thyroid hormone. Current Opin Endocrinol Diabetes Obes 2010; 17: 408–13.
[8] Moller N, Nielsen S, Nyholm B, Porksen N, Alberti KG, Weeke J. Glucose turnover, fuel oxidation and forearm substrate exchange in patients with thyrotoxicosis before and after medical treatment. Clin Endocrinol (Oxf) 1996; 44: 453–9.
[9] S Suleyman et.al. Serum arylesterase and paraoxonase activity in patients with chronic hepatitis.World J Gastroenterol. 11(46); (2005):7351-4.
[10] C Bergmeier, R Siekmeier, W Gross. Distribution spectrum of paraoxonase activity in HDL fractions. Clin. Chem. 50 (12); (2004):2309–15.
[11] H Li, D Liu, C Liang. Paraoxonase gene polymorphisms, oxidative stress, and diseases. J Molecular Medicine. 81 (12); (2003):766–79.
[12] C Ng, D Wadleigh, A Gangopadhyay et al. Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J. Biol. Chem. 276 (48); (2001):44444–9.
[13] S Reddy, D Wadleigh, V Grijalva et.al. Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler. Thromb. Vasc. Biol. 21 (4); (2001):542–7.
[14] S Suleyman et.al. Serum arylesterase and paraoxonase activity in patients with chronic hepatitis. World J Gastroenterol.11(46); (2005):7351-4.
[15] Mooradian AD. Asymptomatic hyperthyroidism in older adults: is it a distinct clinical and laboratory entity?. Pub Med. 2008, 25(5):371-80.
[16] Aldridge WN. Serum esterases. I. Two types of esterase (A and B) hydrolyzing p-nitrophenyl acetate, propionate and butyrate, and a method for their determination. Biochem J 1953; 53:110-7.
[17] Aldridge WN. Serum esterases. II. An enzyme hydrolyzing diethyl p-nitrophenyl phosphate (E600) and its identity with the A-esterase of mammalian sera. Biochem J 1953; 53:117-24.
[18] Sorenson RC, Primo-Parmo SL, Kuo CL, Adkins S, Lockridge O, La Du BN. Reconsideration of the catalytic center and mechanism of mammalian paraoxonase/arylesterase. Proc Natl Acad Sci U S a 1995; 92:7187-91.
[19] Primo-Parmo SL, Sorenson RC, Teiber J, La Du BN. The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics 1996; 33:498-507.
[20] Mackness MI, Hallam SD, Peard T, Warner S, Walker CH. The separation of sheep and human serum "A"-esterase activity into the lipoprotein fraction by ultracentrifugation. Comp Biochem Physiol B 1985; 82:675-7.
[21] Reddy ST, Wadleigh DJ, Grijalva V, Ng C, Hama S, Gangopadhyay A, Shih DM, Lusis AJ, Navab M, Fogelman AM. Human paraoxonase-3 is an HDL associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol 2001; 21:542-7.
[22] Can M, Mungan AG., Acıkgoz Ş, Yuksel B, Demirtaş S, Tomac N. Effect of montelukast treatment on serum paraoxonase activity in asthmatic children. Turk J Med Sci 2007; 37: 373–6.
[23] Videla LA, Fernandez V. Thyroid calorigenesis and oxidative stress: modification of the respiratory burst activity in polymorphonuclear leukocytes. Braz J Med Biol Res 1994; 27: 2331–42.
[24] Moulakakis KG, Poulakou MV, Paraskevas KI, Dontas I, Vlachos IS, Sokolis DP et al. Hyperthyroidism is associated with increased aortic oxidative DNA damage in a rat model. In Vivo 2007; 21: 1021–6.
[25] Lagrost L. Regulation of cholesteryl ester transfer protein (CETP) activity: review of in vitro and in vivo studies. Biochim Biophys Acta. 1994; 1215:209–36.
[26] Kuusi T, Saarinen P, Nikkila EA. Evidence for the role of hepatic endothelial lipase in the metabolism of plasma high density lipoprotein2 in man. Atherosclerosis. 1980; 36:589–93.
[27] Santamarina-Fojo S, Gonzalez-Navarro H, Freeman L, Wagner E, Nong Z. Hepatic lipase, lipoprotein metabolism, and atherogenesis. Arterioscler Thromb Vasc Biol. 2004; 24:1750–4.
[28] Prieur X, Huby T, Coste H, Schaap FG, Chapman MJ, Rodriguez JC. Thyroid hormone regulates the hypotriglyceridemic gene APOA5. J Biol Chem. 2005; 280:27533–43.
[29] Rensen P, Van Dijk K, Havekes L. Apolipoprotein AV: low concentration, high impact. Arterioscler Thromb Vasc Biol. 2005; 25:2445–7.
[30] Engler H and Riesen WF. Effect of thyroid function on concentrations of lipoprotein- a. Clin Chem., 1993; 39: 2466-2469.
[31] Kim CS, Kang JG, Lee SJ, et al. Relationship of low-density lipoprotein (LDL) particle size to thyroid function status in Koreans. Clin Endocrinol (Oxf), 2009; 71: 130-136.
[32] Costantini F, Pierdomenico SD et al. Effect of thyroid function on LDL oxidation. Arterioscler Thromb Vasc Biol., 1998; 18: 732-737.
[33] Ponsin G, Vialle-Valentin C, Berthezene F. Alterations of high density lipoproteins induced by thyroid hormones in man and rat. Adv Exp Med Biol., 1991; 285: 147-154.
[34] Lagrost L. Regulation of cholesteryl ester transfer protein (CETP) activity: review of in vitro and in vivo studies. Biochim Biophys Acta., 1994; 1215: 209-236.
[35] Kung AW, Pang RW, Lauder I, Lam KS, Janus ED. Changes in serum lipoprotein(a) and lipids during treatment of hyperthyroidism. Clin Chem. 1995; 41:226–31.