Study of uric acid, oxidative stress and antioxidant status in hypothyroidism and hyperthyroidism patients

 

Gurupavan Kumar Ganta¹, G S R Kedari^2*, H Ashwin Raj³

 

¹Assistant Professor, ²Professor, ³Tutor, Department of Biochemistry, Saveetha Medical College, Saveetha University, Thandalam, Chennai-602105, Tamil Nadu, INDIA.

Email: gurupawankumar1988@gmail.com, kedari.gsr@gmail.com, ashwinbio4@gmail.com

 

Abstract               Thyroid disorders are more common disorders in India and worldwide. The aim of our present study was to estimate the levels of uric acid, the role of oxidative stress by assessing plasma malondialdehyde (MDA) levels and antioxidant status by estimating the levels of reduced Glutathione (GSH) and Vitamin-C (Ascorbic acid) in hypothyroid and hyperthyroid cases when compared with controls. For this, 50 diagnosed cases of hypothyroid and 50 hyperthyroid cases were included for the study. The findings were compared with 50 age and sex matched controls. A significant increase in the levels of uric acid in hypothyroid cases was observed and no statistical difference was observed between hyperthyroid cases and controls. Statistically significant increase in the levels of MDA and statistically significant decrease in the levels of reduced glutathione (GSH) and Ascorbic acid levels were observed in hypothyroid cases and hyperthyroid cases when compared with controls.

Key Words: Anti-oxidant status, Oxidative stress and Uric acid.

 

 

 

INTRODUCTION

Uric acid is a non-protein nitrogenous (NPN) substance formed during purine catabolism. Uric acid more than 6mg/dl in females and more than 7mg/dl in males is termed as hyperuricaemia. Hyperuricaemia over a period of time leads to deposition of monosodium urate crystals in the joints and surrounding tissues leading to gouty arthritis¹. The global burden of Gout is substantial and seems to be increasing in many parts of the world over the past 50years. Endocrine disorders are common among Indian population out of which thyroid disorders represents an important subset of these endocrine disorders. Thyroid disorders hypo and hyperthyroidism are associated with alterations in metabolism of various substances including uric acid. Many studies showed the association between hypothyroidism and hyperuricaemia^2,3 and the association between hyperthyroidism and hyperuricaemia has been controversial. A lot of studies have been done to prove the association between uric acid levels and thyroid disorders. But most of these studies have been done in the western population and north Indians. Uric acid levels have been shown to vary with ethnicity^2,3. In normal cell, there is an appropriate pro-oxidant-antioxidant balance. This balance is shifted towards pro-oxidants when the production of oxygen species is increased or the levels of the antioxidants are decreased and this state is called as ‘oxidative stress’. Oxidative stress is implicated in the pathogenesis of variety of human diseases⁴. Oxidative damage occurs to biomolecules like lipids, proteins, carbohydrates and nucleic acids and other extracellular components like collagen and hyaluronic acid which are very deleterious⁵. The formation of lipid peroxides by action of free radicals on unsaturated fatty acids has been implicated in the pathogenesis of atherosclerosis and vascular diseases⁶. The body’s defense mechanism plays an important role in the form of antioxidants that help to minimize the damages which are caused by oxidative stress. Antioxidants are compounds that dispose, scavenge and suppress the formation of free radicals or oppose their actions⁷. Hence, the present study was undertaken to assess the uric acid levels, the extent of lipid per-oxidation and the status of the antioxidant defense mechanisms in patients of hypo and hyper thyroidism.

 

MATERIALS AND METHODS

The present study was conducted in the department of biochemistry, Saveetha medical college, Thandalam. 50 newly diagnosed cases of hyperthyroidism and 50diagnosedcases of hypothyroidism were chosen for the study, which belong to the age group of 25-50years. 50 age matched and sex matched without any thyroid disorders were taken as controls. Subjects with known cases of diabetes mellitus, hypertension, renal disorders, rheumatoid arthritis, gout, smoking, alcoholism, patients taking allopurinol and probenecid were excluded from study. Informed consent was obtained from all of them.10ml of fasting blood samples were collected, the separated serum was used to estimate serum uric acid levels. Uric acid is estimated by uricase enzymatic method (uricaseand per-oxidase) method in clinical biochemistry laboratory. The plasma MDA levels were estimated by using thiobarbituric acid reacting substance (TBARS) by the method Yagi⁸ and Sinnhuber et al⁹. Reduced glutathione was determined by the method of Beutler et al¹⁰ and ascorbic acid was determined by the method of Tietz¹¹. All the results were expressed as ±SD and statistical comparisons were done. Due permission was obtained from the institutional ethics committee prior to the starting of the work.

 

RESULTS

 

Table 1:

 

Table 2:

 

Table 3:

 

Table 4:

 

 

DISCUSSION

In our present study, there is statistical significant difference in the levels of uric acid in hypothyroid cases when compared with controls and no statistical significant difference was observed in the levels of uric acid in hyperthyroid cases when compared with controls. Statistical significant difference were observed in the levels of MDA, reduced glutathione and Vitamin-C levels between hypothyroid cases and controls and also hyperthyroid cases and controls. In the present study, there is statistical significance increase in uric acid levels in hypothyroid cases when compared with euthyroid subjects, this fact suggests that hypothyroid in hyperuricemia is secondary to a reduction in renal plasma flow and glomerular filtration^12,13 secondary to thyroid hormone deficiency. Our study supports the studies where correlation between hypothyroidism and hyperuricaemia is well established.(14,15,16). In present study no statistical association is observed in uric acid levels between hyperthyroid and normal controls. Our study is in association with some studies¹⁷ which showed no correlation in uric acid levels and contrary to some studies^18,19 which showed statistical association between hyperthyroid cases and euthyroid controls showing that hyperthyroidism can cause hyperuricaemia through the increase of purine nucleotide turnover and decrease of renal urate excretion. Our results showed that the MDA levels, an index of lipid peroxidation and reduced glutathione and vitamin –C levels of antioxidant status were modified in hypothyroidism and hyperthyroidism when compared with controls, indicates oxidative stress in hypothyroid and hyperthyroid cases. Our results are in agreement with some authors, who observed that there is significant alteration of plasma TBARS in hypothyroidism when compared to euthyroid subjects.^20,21. However, other authors observed that TBARS is not altered in subclinicalhypothyroidism cases compared to Euthyroid subjects.²² Oxygen free radicals plays an important role in the pathogenesis of several conditions including hypothyroidism and hyperthyroidism^23,24,25. Some authors suggest that tissues may be protected from oxidant damage because of a hypometabolic state in hypothyroidism²⁶, whereas some other studies suggest that oxidative stress is increased in hypothyroidism²⁷. ROS can attack double bonds in PUFA, and thus include lipid per-oxidation; this in turn results in more oxidative damage²⁶. Similar to our studies some authors found increased markers of Oxidative stress in patients with graves disease which leads to hyperthyroid state.²⁸ and thyroid antibodies may be seen in various disorders like type-1 diabetes mellitus²⁹. Our study shows oxidative stress is implicated in the pathogenesis of hypothyroidism and hyperthyroidism and extensive studies are required to reduce the morbidity in these cases.

 

REFERENCES

• Lippincott illustrated reviews biochemistry 5^th edition page no.299.
• Yokogoshi Y, Saito S: Abnormal serum uric acid level in endocrine disorders: Nihon Rinsho. 1996;54(12):3360-3.
• Chaudhury HS, Raihan KK, UddinMN, Ansari SM, Hasan M, Ahmed M et al: Renal function impairment in hypothyroidism: Bangladesh J Med Biochem. 2013; 6(1):19-25.
• Beck MM, Levander OA: Dietary oxidative stress and potentiation of viral infection: Annu Rev Nutr. 1998; 18:93-116.
• Frei B: Reactive oxygen species and antioxidant vitamins: mechanisms of action: Am J Med. 1994; 97:S5-S13.
• Donald DH: Oxidative stress and vascular disease: Arterioscler Thromb Vasc Biol. 2005; 26:689-695.
• Kedari GSR: Evaluation of the Thyroid status, Oxidant stress and Antioxidant status in patients with Type-2 Diabetes Mellitus: Journal of Clinical and Diagnostic Research. 2011 Apr; Vol-5(2):254-256.
• Yagi K: Lipid peroxidases and human diseases: Chem Phys Lipids. 1978; 45:337-351.
• Sinnhuber RO, Yu TC, Yu TC: Characterization of red pigment formed in thiobarbituric acid determination of oxidative rancidity: Food Res. 1958; 23:626-630.
• Beutler E, Duron O, Kelly BM: Improved method for determination of blood glutathione: J Lab Clin Med. 1963; 61:882-888.
• TietzNW Textbbok of Clinical Chemistry.W.B.Saunders Company, Philadelphia, London, Tornoto.2004; pp.960-962.
• Steiger MJ, Watson AR, Morgan: Hypothyroidism and renal impairment: JR Soc Med. 1991; 84:688-9.
• Mclanghlin KJ, Mactier RA: Renal impairment in hypothyroidism: Nephrol Dial transplant. 1994; 9:1521-2.
• Makino Y, Fujit T, Kuroda S et al: Exacerbation of renal failure due to hypothyroidism in a patient with ischemic nephropathy: Nephron. 2000; 84:267-9.
• Montenegroj, Gonzaleso, Sarachor et al: Changes in renal function in primary hypothyroidism: Am J kidney Dis. 1996; 27:195-8.
• Mooraki A, Bastani B: Reversible renal insufficiency, hyperuricemia and gouty arthritis in a case of hypothyroidism: Clin Nephrol. 1998; 49:59-61.
• Raber W, Vukovich T, Vierhapper H: Serum uric acid concentration and thyroid stimulating hormone (TSH): Results of screening for hyperuricemia in 2359 consecutive patients with various degrees of thyroid dysfunction: Wien Klinwochenschr. 1999; 111:326-8.
• Fordh C, Lim WC, Chisnall WN, Pearce JM: Renal function and electrolyte levels in hyperthyroidism: urinary protein excretion and plasma concentration of urea, Creatinine, uric acid, hydrogen ion and electrolytes: Clin Endocrinol. 1989; 30:293-301.
• Sato A, Shirota T, Shinoda T et al: Hyperuricemia in patients with hyperthyroidism due to Grave’s disease: Metabolism. 1995; 44:207-11.
• Nanda N, Bobby Z, Hamide A et al: Association between oxidative stress and coronary lipid risk factors in hypothyroid women is independent of body mass index: Metabolism. 2007; 56:1350-5.
• Erdamar H, Demiric H, Yaman H et al: The effect of hypothyroidism, hyperthyroidism and their treatment on parameters of oxidative stress and antioxidant status: Clin Chem lab Med. 2008; 46:1004-10.
• Kebapcliar L, Akinci B, Bayraktar F et al: Plasma thiobarbituric acid reactive substance levels in subclinical hypothyroidism: Med Princ Pract. 2007; 16:432-6.
• Paller MS: Hypothyroidism protects against free radical damage in ischemic acute renal failure: Kidney Int. 1986; 29:1162-1166.
• Dumitriu L, Bartoc R, Ursu H et al: Significance of high levels of serum malonyldialdehyde(MDA) and ceruloplasmin(CP) in hyper and hypothyroidism: Endocrinology. 1988; 26:35-38.
• Costantini F, Pierdomenico SD, Cesare D De, Remigis P De, Bucciarelli T, Bittolo Bon G, Cazzolato G, Nublie G, Guanano MT, Sensi S, Cuccurullo F, Mezzetti A: Effect of thyroid function on LDL oxidation: Arterioscler ThrombVasc Biol. 1998; 18:732-737.
• Pereira B, Rosa LF, Safi DA et al: Control of superoxide dismutase, catalase and glutathione peroxidase activities in rat lymphoid organs by thyroid hormonrs: J Endocrinol. 1994; 140:73-77.
• Sundaram V, Hanna AN, Koneru L et al: Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation: J Clin Endocrinol Metab. 1997; 82:3421-3424.
• M. Abalovich, S. Llesuy, S. Gutierrez, and M. Repetto: Peripheral parameters of oxidative stress in Grave’s disease: The effect of methimazole and 131 iodine treatments: Clinical Endocrinology. 2003; 59(3): 321-327.
• G S R Kedari: Estimation of thyroid hormone status and thyroid antibodies in type-1 diabetes mellitus: Indian J.Sci.Technol. 2010; 3(9): 1014-15.