|Year : 2018 | Volume
| Issue : 1 | Page : 34-37
Vitamin D and primary hypothyroidism: Is there an association?
Jyothi Idiculla1, Pooja Prabhu1, Rekha Pradeep1, Kranti Khadilkar2, Subramanian Kannan2
1 Department of Medicine, St. John's Medical College, Bengaluru, Karnataka, India
2 Mazumdar Shaw Medical Centre, Narayana Health City, Bengaluru, Karnataka, India
|Date of Web Publication||23-Mar-2018|
Dr. Subramanian Kannan
Mazumdar Shaw Medical Centre, Narayana Health City, Bomassandra Anekal, Bengaluru - 560 099, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Association studies between the vitamin D deficiency (VDD) and hypothyroidism have given mixed results. Because of this controvery and relatively common prevalence of these two conditions, we conducted a case-control study investigating the prevalence of VDD in patients with hypothyroidism (both TPO-Ab positive and negative) and compared it with euthyroid controls.
Methodology: This is a single centre cross sectional study. Adults (aged 18 years or more) of both the sexes diagnosed with primary hypothyroidism (TSH >5.1 mIU/L) were included (n = 115) along with age and sex matched euthyroid (TSH <5 mIU/ml) controls (n = 120) chosen from the outpatients' department. Biochemical parameters like Thyroid stimulating hormone (TSH), free T4 (fT4), 25 hydroxy vitamin D (Vit D) and thyroid peroxidase antibody (TPO-Ab) were tested in both the groups.
Results: Patients in the hypothyroid group [38 (males) and 77 (females)] had a mean (SD) age 46 (15) years, while the euthyroid control group [24 (males) and 96 (females) had a mean (SD) age of 45 (17) years. In the hypothyroid group, 96% (110/115) had VDD as compared to 90% (108/120) in the control group with a significantly lower mean Vit D level was observed in the hypothyroid group as compared to the euthyroid group (12+8.6 vs 17.49+11.89 ng/ml; P < 0.001). While 27 cases with hypothyroidism had severe VDD (Vit D levels <4.2 ng/ml) only 10 among the control group had severe VDD (OR 2.04, CI: 1.03-4.05, P < 0.05)). The mean level of Vit D in the TPO-Ab positive hypothyroid group was 10.4+7.2 ng/ml in comparison to the TPO-Ab negative group 15.3+10.3 (P = 0.004) (OR 3.39, CI:1.18-9.80; P < 0.05) 3.62).
Conclusion: The vitamin D levels in patients with hypothyroidism were significantly lower compared to euthyroid controls.TPO-Ab positive patients had lower levels of vitamin D in comparison with negative
Keywords: Hypothyroidism, primary hypothyroidism, vitamin D deficiency
|How to cite this article:|
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
|How to cite this URL:|
Idiculla J, Prabhu P, Pradeep R, Khadilkar K, Kannan S. Vitamin D and primary hypothyroidism: Is there an association?. Thyroid Res Pract [serial online] 2018 [cited 2019 Nov 15];15:34-7. Available from: http://www.thetrp.net/text.asp?2018/15/1/34/228382
| Introduction|| |
Vitamin D deficiency (VDD) is now established to be rampant and is being investigated as a contributory factor to many diseases. This sunshine vitamin is reported to be deficient in the Indian population, despite the abundance of sunlight in this country. Hypothyroidism is estimated to be prevalent in 11% of the Indian population, with 9% being subclinically hypothyroid., The association studies between VDD and primary hypothyroidism have given mixed results.
The high prevalence of hypothyroidism and VDD in the Indian population provided us a unique opportunity to assess the association between these two variables., Hence, we conducted a case–control study investigating the prevalence of VDD in patients with hypothyroidism. The study also compared Vitamin D levels between Thyroid peroxidase antibody (TPO-Ab) positive and TPO-Ab negative patients as well between hypothyroid patients and euthyroid controls.
| Methodology|| |
This is a single-center cross–sectional wherein after the Institutional Ethics Committee approval and written informed consent, adults (aged 18 years or more) of both the sexes diagnosed with primary hypothyroidism were enrolled for this study. Patients with post radioiodine hypothyroidism, hepatic or renal dysfunction, on anti- epileptic medications or vitamin D supplementation were excluded from the study. Age- and sex-matched euthyroid controls were chosen from the Department of Medicine. A detailed history and clinical examination were performed to identify the signs and symptoms related to hypothyroidism and/or VDD. Thyroid-stimulating hormone (TSH), free T4 (fT4), TPO-Ab titers, and 25 hydroxy Vitamin D levels were assayed for each patient in the primary hypothyroidism group. Vitamin D levels were assayed for the control group with normal TSH.
Assays and ranges
The biochemical parameters were assayed in the Department of Biochemistry attached to our institution. Chemiluminescence enzyme immunoassay (CLIA) was used for TSH and FT4, whereas enhanced CLIA (E-CLIA was utilized for assaying Vitamin D (total 25 hydroxy Vitamin D). Chemiluminescent microparticle immunoassay was used for analysis of TPO-Ab. The Endocrine Society Clinical Practice Guidelines were used to define VDD (<20 ng/ml), insufficiency cb (20–30 ng/ml) and sufficiency (>30 ng/ml). As per laboratory norms levels <4.2 ng/ml were classified as severe VDD. The normal ranges for TSH and fT4 were 0.5–5 IU/ml and 0.76–1.79 ng/dl, respectively, in the laboratory where tests were performed. TSH values >5.1 IU/ml were enrolled into the study.
Sample size and statistical analysis
Based on the previous study a sample size of 110 each group was calculated with a power of 80% and an alpha error of <0.05. The mean standard deviation (SD) and the range were calculated for all continuous variables. Student's t-test was used to compare the means of TSH, Vitamin D levels between the different groups (hypothyroid and euthyroid). Chi-square test was used to compare the prevalence of severe VDD among the TPO-Ab positive and negative groups. Statistical analysis was performed using the software SPSS for Windows version 18.0 (IBM SPSS Statistics for Windows, Version 18.0. Armonk, NY: IBM Corp was used for all analyses). The value of P < 0.05 was considered statistically significant.
| Results|| |
A total of 235 patients were enrolled into the study, of which 115 (77 F; mean age 46 ± 15 years) had primary hypothyroidism (3 had subclinical hypothyroidism) and 120 (96 F; mean age 45 ± 17 years) were euthyroid controls. In the hypothyroid group, 96% (110/115) had VDD as compared to 90% (108/120) in the control group. Mean Vitamin D level was significantly lower in the hypothyroid group than the euthyroid group (12 ± 8.6 SD vs. 17.49 ± 11.89 SD [ng/ml]; P < 0.001) [Graph 1]. While 27 cases with hypothyroidism had severe VDD (Vitamin D levels <4.2 ng/ml) only 10 among the control group had severe VDD (odds ratio [OR] 2.04, confidence interval [CI]: 1.03–4.05, P < 0.05).
Two-thirds (77/115) of the hypothyroid group tested positive for TPO-Ab. The mean level of Vitamin D in the TPO-Ab positive hypothyroid group was 10.4 ± 7.2 ng/ml, compared to the TPO-Ab negative group 15.3 ± 10.3 (P = 0.004). One-third (23/77) of those with positive antibody had severe VDD as compared to 10% (4/38) in the antibody negative group (OR 3.39, CI: 1.18–9.80; P < 0.05) 3.62) [Graph 2].
There was a declining trend of Vitamin D levels with rising titers of TPO-Ab [Graph 3]. However, a direct correlation between Vitamin D levels and TPO-Ab did not show any significance (R = 0.15, P = 0.18).
| Discussion|| |
In this study, comparing Vitamin D levels between patients with hypothyroidism and euthyroid controls, 93% were observed to be deficient. Although the prevalence of VDD was not significantly different between patients with hypothyroidism and euthyroidism, there was a significantly higher proportion of severe VDD (<4.2 ng/dl) in the group with hypothyroidism. The OR for hypothyroidism in the severely VDD group was 2. 04. The mean levels of Vitamin D were significantly lower in the group with hypothyroidism. These point to higher possibility of hypothyroidism in individuals deficient in Vitamin D. Among those with hypothyroidism TPO-Ab positive patients had a lower mean level of Vitamin D, and there was a significantly higher number of patients with severe VDD in this group.
VDD has been reported to be widely prevalent in India and the overall prevalence of VDD in our study concurs with this.,,, In patients with hypothyroidism the levels of Vitamin D were lower with a high OR in patients severe VDD. A study from Meerut on 152 hypothyroid subjects reported a similar association between Vitamin D and hypothyroidism. The mean levels of Vitamin D in the subclinically hypothyroid, overt hypothyroid, and controls were 16.73 ± 12.46 ng/ml, 13.23 ± 10.08 ng/ml, and 29.07 ± 19.01 ng/ml. The levels were significantly lower in patients with hypothyroidism as compared to controls similar to our results.
Seventy-seven out of 115 patients tested positive for TPO-Ab. It is known that autoimmunity is the most common etiology and about 10% of patients with autoimmune thyroid disease (AITD) may not have detectable antibodies in the serum., A recent meta-analysis of 20 case–control studies concluded that compared to controls AITD patients had lower mean levels of Vitamin D which is in agreement with our results. The OR for patients with VDD to be hypothyroid was 2.99 (95% CI 1.88,4.74). In India, Goswami et al. reported an association between TPO-Ab and Vitamin D which was not strong enough to conclude the protective effects of Vitamin D on thyroid autoimmunity. Another study from Benares reported significantly lower levels of Vitamin D in AITD. In this study patients with autoimmune hypothyroidism were found to have mean Vitamin D level of 15.67 ± 5.61 ng/dl while nonhypothyroid controls were Vitamin D sufficient (31.39 ± 4.63 ng/dl). Similar observations were reported by studies from other parts of the world also., Kivity et al.so observed that patients with higher Vitamin D levels had lesser titers of thyroid antibodies. These findings suggest the possible role of Vitamin D in the development of autoimmunity.
The change in dynamics of immune cells, especially dendritic cells and T lymphocytes and their products may be contributory to this phenomenon. In a recent Indian study supplementation of Vitamin D to TPO-Ab positive individuals resulted in a reduction of antibody titers, reiterating the role of Vitamin D in antibody production. It is also of interest that Vitamin D has been implicated in connective tissue diseases and studies are ongoing to define the effects of Vitamin D supplementation in these conditions.
The main strength of the study is the control group and the inclusion of adequate study participants. However, the study was powered to detect VDD in hypothyroidism not TPO-Ab positive hypothyroidism. The other limitations are the absence of prospective data and lack of thyroglobulin antibody levels. TPO-Ab was not assayed in the euthyroid control group, and this may also be a drawback.
| Conclusions|| |
VDD is prevalent in both hypothyroid and euthyroid subjects with significantly lower levels of Vitamin D in antibody-positive hypothyroid patients, suggesting that lower serum Vitamin D may be related to autoimmune hypothyroidism. Large multi-center randomized controlled trials would definitely help to conclude whether there is an actual association between Vitamin D and thyroid autoimmunity and determine the beneficial effect of Vitamin D supplementation in such patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: A systematic review. Lancet Diabetes Endocrinol 2014;2:76-89.
GR, Gupta A. Vitamin D deficiency in India: Prevalence, causalities and interventions. Nutrients 2014;6:729-75
Bagcchi S. Hypothyroidism in India: More to be done. Lancet Diabetes Endocrinol 2014;2:778.
Unnikrishnan AG, Kalra S, Sahay RK, Bantwal G, John M, Tewari N, et al.
Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian J Endocrinol Metab 2013;17:647-52.
Wang J, Lv S, Chen G, Gao C, He J, Zhong H, et al.
Meta-analysis of the association between Vitamin D and autoimmune thyroid disease. Nutrients 2015;7:2485-98.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al.
Evaluation, treatment, and prevention of Vitamin D deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-30.
Beloyartseva M, Mithal A, Kaur P, Kalra S, Baruah MP, Mukhopadhyay S, et al.
Widespread Vitamin D deficiency among indian health care professionals. Arch Osteoporos 2012;7:187-92.
Marwaha RK, Tandon N, Garg MK, Kanwar R, Narang A, Sastry A, et al.
Vitamin D status in healthy Indians aged 50 years and above. J Assoc Physicians India 2011;59:706-9.
Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D. Vitamin D status in Andhra Pradesh: A population based study. Indian J Med Res 2008;127:211-8.
] [Full text]
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.
Almandoz JP, Gharib H. Hypothyroidism: Etiology, diagnosis, and management. Med Clin North Am 2012;96:203-21.
Knobel M, Barca MF, Pedrinola F, Medeiros-Neto G. Prevalence of anti-thyroid peroxidase antibodies in autoimmune and nonautoimmune thyroid disorders in a relatively low-iodine environment. J Endocrinol Invest 1994;17:837-42.
Prasad I, Kumari R, Saran A. Vitamin D evaluation in autoimmune thyroid diseases. Int J Contemp Med Res 2015;83:2393-15.
Tamer G, Arik S, Tamer I, Coksert D. Relative Vitamin D insufficiency in Hashimoto's thyroiditis. Thyroid 2011;21:891-6.
Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K, et al.
Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol 2011;8:243-7.
Hewison M. Vitamin D and the immune system: New perspectives on an old theme. Endocrinol Metab Clin North Am 2010;39:365-79.
Chaudhary S, Dutta D, Kumar M, Saha S, Mondal SA, Kumar A, et al.
Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labeled randomized controlled trial. Indian J Endocrinol Metab 2016;20:391-8.
Reynolds JA, Bruce IN. Vitamin D treatment for connective tissue diseases: Hope beyond the hype? Rheumatology (Oxford) 2017;56:178-86.