Case control study on vitamin D deficiency and risk of hypothyroidism

Abstract               Indian population has been found to be deficient in Vitamin D. Vitamin D deficiency is supposed to be associated with hypothyroidism. The present study was conducted to find the association between Vitamin D deficiency and hypothyroidism. The study design was case-control. The cases were selected from the patients suffering from hypothyroidism and controls were selected from those accompanying patients with age and sex matching in the ratio of 1:1. It was observed that there is significant association between hypothyroidism and Vitamin D deficiency (p<0.05). The risk of hypothyroidism is increased with Vitamin D deficiency.

Key Word: Case Control Study, Hypothyroidism, Vitamin D Deficiency

INTRODUCTION

Vitamin D deficiency is emerging as important health problem globally. Nearly one billion people are estimated to be suffering from this condition worldwide¹. It has multifarious functions right from its role in calcium and phosphorus metabolism to actions on myocardium, pancreas, and thyroid etc². Its actions are mediated through Vitamin D receptors which are present throughout the body. Vitamin D deficiency is an established risk factor for diabetes mellitus³, atherosclerosis⁴, infections⁵ and autoimmune diseases⁶. India, being a tropical country has plenty of sunshine available. But, Indian population has been found to be deficient in Vitamin D⁷. Prevalence of hypothyroidism is reported to be 11% in India⁸ and 42 million people are estimated to suffer from this condition in India⁹. Vitamin D deficiency is supposed to be associated with hypothyroidism. But, different researchers have found varying results¹⁰. Hence, the present study was conducted to explore this issue. Research question- Is Vitamin D deficiency associated with hypothyroidism? Aims & objectives- The present study was conducted to find the association between Vitamin D deficiency and hypothyroidism.

MATERIAL AND METHODS

The present study was conducted at the Department of Biochemistry, Patna Medical College in case-control design. The cases were selected from the patients suffering from hypothyroidism who came for treatment at Medicine OPD of Patna Medical College and were found to be suffering from hypothyroidism on clinical examination and biochemical confirmation. Cases were selected in the age group of 18-35 years. The patients who were getting treatment for hypothyroidism and those suffering from kidney & liver diseases, diabetes and joint diseases were excluded. Controls were selected from those accompanying patients who were healthy, were not suffering from hypothyroidism and did not have family history of thyroid diseases. Age (± 1 year) and sex matching of cases and controls was done in the ratio of 1:1. Detailed clinical history was taken from all the study subjects and thorough clinical examination was done. This was followed by collection of venous blood after 12 hours fast for estimation of plasma glucose, serum creatinine and blood urea using Photometer 5010¹¹. It is Semi-automated Analyser of single beam filter photometer type. It has halogen lamp of wavelength340 nm to 800 nm. Roche electrolyte analyzer¹² was used for serum calcium. It is designed to quickly and accurately conduct whole blood electrolyte testing in the laboratory or point of care. The six electrodes in the Electrolyte Analyzer measure sodium, potassium, chloride, ionized calcium, lithium with the use of the reference electrode. It gives electrolyte results from just 95 ul of whole blood, serum, plasma, acetate or bicarbonate dialysate, or pre-diluted urine. Several kinds of sample container - collection tube, syringe, capillary or sample cup, Roche Microsampler - can be presented to the instrument probe for sampling. AccuLite CLIA analyzer was used for estimation of levels of T3, T4, TSH and Vitamin D. Vitamin D levels < 20 ng/ml was considered to be the level for labelling as Vitamin D deficiency as per Endocrine Society Clinical Practice Guidelines¹³. A total of 60 controls matched for age and sex along with equal number of cases were selected for the present study. Data was entered into Microsoft Excel 2007 and analyzed using SPSS v 16.0. Frequency and percentage were calculated for categorical variables and Mean ± SD for continuous variables. For the tests of hypothesis, Chi-Square test, Student T test, Fischer test and Mann-Whitney test was done as appropriate for the variables. p-value < 0.05 was considered as statistically significant.

RESULTS AND DISCUSSION

The present study included 60 age and sex matched cases and controls. Table-1 shows the background profile of cases and controls. The controls were matched for age with cases up to ± 1 year. Mean age of cases was 29.7 ± 3.4 years and that of controls was 29.1 ± 3.7 years and this difference was not significant statistically (p= 0.4). The sex distribution of cases and controls was similar (p=1). The differences in religion (p=0.5) and economic status (p=0.7) was not significant statistically. This indicates that the socio-demographic profile of cases and controls was similar.

Similar observations have been reported by other researchers in the studies conducted at different places of India. Koch et al¹⁴ in their study done in Meerut found that the mean value of vitamin D in subclinical hypothyroid and overt hypothyroid were significantly lower than the euthyroid (29.07±19.01 ng/ml). There was significant negative correlation between vitamin D and TSH (r=-0.314, P<0.01). Jayakumari et al¹⁵ explored vitamin d deficiency as a risk factor for auto immune thyroiditis in south Indian population and concluded that Serum25-OH-D levels < 20 ng/ml was more common in patients with autoimmune thyroiditis than controls (odds ratio=17.9). Idiculla et al¹⁶ have observed that 96% hypothyroid individuals had Vitamin D deficiency as compared to 90% controls. Sonawane et al¹⁷ concluded that Vitamin D deficiency correlated with increase in levels of TSH. There was progressive decrease in level of Vitamin D from subclinical to overt hypothyroidism. A negative and significant correlation was observed by Lohokare et al¹⁸ between 25(OH) Vitamin D and TSH levels (r= -0.45, p < 0.001). The findings of this study are in line with studies conducted at other parts of the country and it estimates the risk of hypothyroidism to be 9.14 times. It has been found that Vitamin D has important role in various metabolic processes of the body². Its etiological role in causation of autoimmune diseases is being explored⁶. VDR gene variations are supposed to mediate susceptibility to various endocrinal autoimmune diseases¹⁹. Vitamin D and thyroid hormones both act via steroid receptors and hence, any alteration in the level of Vitamin D is likely to increase problems associated with hypothyroidism²⁰.

Chart 1: showing biochemical profile of cases and controls

CONCLUSION

The findings of the present study indicated that there is significant association between hypothyroidism and Vitamin D deficiency (p<0.05). The risk of hypothyroidism is increased with Vitamin D deficiency. Large scale studies are needed to find the causality of hypothyroidism. Interventional studies can also be conducted to assess the effectiveness of Vitamin D supplementation in preventing hypothyroidism.

REFERENCES

• Hollick MF, Chen TC. Vitamin D deficiency a worldwide problem with health consequences. Am J Clin Nutr.2008; 87:10805-68.
• Norman, A.W. 2008. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am. J. Clin. Nutr., 88(suppl):S491–9.
• Pittas AG, Lau J, Hu FB et al. The role of vitamin D and calcium in type 2 diabetes: a systematic review and meta analysis. J Clin Endocrinol Metab 2007; 92(6):2017-29.
• Kendrick J, Targher G, Smits G et al. 25 hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the third national health and nutrition examination survey. Atherosclerosis 2009; 205(1):255-60.
• Scragg R, Sowers M, Bell C. Serum 25 hydroxyvitamin D, diabetes and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 2004; 27(12):2813-8.
• Forman JP, Giovannucci E, Holmes MD et al. Plasma 25 hydroxyvitamin D levels and risk of incident hypertension. Hypertension 2007; 49(5):1063-9.
• Ritu G, Gupta A. Vitamin D deficiency in India: Prevalence, Causalities and Interventions. Nutrients 2014, 6, 729-775.
• Unnikrishnan GA, Usha MV. Thyroid disorders in India: An epidemiological perspective. Indian J Endcrinol Metab 2011; 15(Suppl2):S78-81.
• Usha MV, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair V K. High prevalence of undetected thyroid disorders in an iodine sufficient adult south Indian population. J Indian Med Assoc 2009; 107:72-7.
• Prabha AGT. Reliable Earlier and Causative Biomarker in newly Diagnosed Hypothyroid Cases Vitamin D: A Case control Study. Indian journal of Medical Biochemistry 2017; 21(1): 54-7.
• https://www.diasys.in/lab-diagnostics/clinical-chemistry-immunoturbidimetry/instruments/photometer-5010/ accessed on 12/11/2018.
• https://diagnostics.roche.com/ph/enus/products_and_solutions/point-of-care/blood-gas-and-electrolytes/9180-electrolyte-analyzer.html accessed on12/11/2018.
• https://academic.oup.com/jcem/article/96/7/1911/2833671 accessed on12/11/2018.
• Koch N, Kaur J, Mittal A, Gupta A, Pal Kaur I, Agarwal S, et al. Status of Vitamin D levels in hypothyroid patients and its associations with TSH, T3 and T4 in North Indian population of Meerut, a cross sectional study. Int J Clin Biochem Res 2016;3:295-8
• Jayakumari C, Jayakumar B,  Jabbar PK, Nair A,Beegum SM, Pillai RT. Vitamin D Deficiency - A Risk Factor for Auto Immune Thyroiditis. International Journal of Current Innovation Research 2016; 3 (07):715-8.
• Idiculla J, Prabhu P, Pradeep R, Khadilkar K, Kannan S. Vitamin D and primary hypothyroidism: Is there an association?. Thyroid Res Pract 2018; 15: 34-7.
• Sonawane S, Bora B, Shrikhande DY, Bansal S, Kumar P. Vitamin D deficiency and its association with thyroid diseases. International Journal of Contemporary Medical Research 2017; 4(8):1765-1767.
• Lohokare R, Gupta A, Jain A, Kothari V, Sarkar PD. A Study of Vitamin D Levels In Hypothyroid Patients, a Case Control Study in a Tertiary Care Hospital of Central India. National Journal of Medical and Dental Research 2016; 4 (2): 89-92.
• Pani MA, Knapp M, Donner H, Braun J, Baur MP, Usadel KH et al. Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans. Diabetes 2000; 49: 504–507.
• Wang TJ, Pencina MJ, Booth SL et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008; 117: 503-11.