|Year : 2017 | Volume
| Issue : 2 | Page : 64-70
Effect of vitamin D3 in treating hyperthyroidism in patients with graves’ disease
Nermin A Sheriba1, Abeer A.A. Elewa PhD 1, Maram M Mahdy1, Ahmed M Bahaa El Din1, Nesma A Ibrahim1, Dina A Marawan1, Tahany M Abd El Moneim2
1 Department of Internal Medicine, Ain Shams University, Cairo, Egypt
2 Department of Biochemistry, Ain Shams University, Cairo, Egypt
|Date of Submission||09-Mar-2017|
|Date of Acceptance||27-Apr-2017|
|Date of Web Publication||14-Aug-2017|
Abeer A.A. Elewa
31 Police Building, Kornish El-Nile, Al Maadi, Cairo
Source of Support: None, Conflict of Interest: None
Graves’ disease (GD) is an autoimmune disease characterized by hyperthyroidism secondary to circulating autoantibodies. Multiple factors contributed to its etiology, including genetic and environmental factors. The role of vitamin D is well-known in calcium metabolism and skeletal homeostasis. Vitamin D was shown to be a modulator in both innate and adaptive immunity. There is a link between vitamin D deficiency and various autoimmune diseases. The prevalence of vitamin D deficiency was reported to be common in patients with GD. Interestingly, vitamin D deficiency is found to be associated with higher thyroid volume in patients with newly-onset GD. However, vitamin D deficiency relationship with GD remains a controversial issue.
The objective of this study was to evaluate the effect of vitamin D supplementation in GD with and without ophthalmopathy.
Patients and methods
A randomized prospective study was conducted on 60 adult patients with GD aged 20–40 years. Group 1 comprised 20 patients with GD receiving a daily dose of 30 mg of methimazole alone. Group 2 comprised 40 patients with GD receiving the same dose of methimazole, supplemented with intramuscular injection of vitamin D3 200 000 IU/month for 3 months. Patients were followed up over a 3-month duration.
There was hypovitaminosis D in all participants with a percentage of vitamin D deficiency (vitamin D level: <20 ng/ml) of 73.9% in male and 54.1% in female and a vitamin D insufficiency (vitamin D level: 20–29 ng/ml) of 26.1% in male and 45.9% in female. Vitamin D was significantly correlated with thyroid volume and degree of exophthalmos. On vitamin D supplementation, group 2 had significantly lower thyroid volume and better effect on the degree of exophthalmos.
Vitamin D supplementation for GD has a favorable effect on thyroid volume and on the degree of exophthalmos.
Keywords: exophthalmos, Graves’ disease, vitamin D
|How to cite this article:|
Sheriba NA, Elewa AA, Mahdy MM, Bahaa El Din AM, Ibrahim NA, Marawan DA, Abd El Moneim TM. Effect of vitamin D3 in treating hyperthyroidism in patients with graves’ disease. Egypt J Intern Med 2017;29:64-70
|How to cite this URL:|
Sheriba NA, Elewa AA, Mahdy MM, Bahaa El Din AM, Ibrahim NA, Marawan DA, Abd El Moneim TM. Effect of vitamin D3 in treating hyperthyroidism in patients with graves’ disease. Egypt J Intern Med [serial online] 2017 [cited 2019 Jul 19];29:64-70. Available from: http://www.esim.eg.net/text.asp?2017/29/2/64/212930
| Introduction|| |
Vitamin D has a well-known role in calcium metabolism and skeletal homeostasis. Recently, vitamin D proved to be a modulator in both innate and adaptive immunity . Vitamin D deficiency has an established link with various autoimmune diseases, including type1 diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. Furthermore, it has been found that the supplementation of vitamin D can prevent the onset and/or development of different kinds of autoimmune disorders in human beings and animal models .
Graves’ disease (GD) is an autoimmune thyroid disease (AITD) characterized in its typical presentation by association of thyrotoxicosis, goiter, and ophthalmopathy. It is a multifactorial disease caused by a complex interaction between genetic and environmental factors that lead to the loss of immune tolerance to thyroid antigens, and therefore to the initiation of an immune reaction against the thyroid .
Several studies discovered the association between vitamin D levels and GD ,,,,,,,,,,. Vitamin D deficiency is common in patients with GD and associated with higher thyroid volume ,. Vitamin D receptor gene polymorphisms were found to be associated with the risk for GD .
| Aim|| |
The aim of this work was to evaluate the effect of vitamin D supplementation in GD patients with and without ophthalmopathy on the progress of their condition.
| Patients and methods|| |
A randomized open prospective study was conducted on 60 adult patients with GD aged 20–40 years who were recruited from the Endocrinology Clinic, Ain Shams University, in winter–spring periods in 2015–2016.
All patients were diagnosed with GD and divided by computer-generated randomization into two groups.
Group 1: 20 patients with GD received a daily dose of 30 mg of methimazole (MMI); 10 of them were diagnosed with Graves’ ophthalmopathy.
Group 2: 40 patients with GD received 30 mg of MMI and were supplemented with vitamin D3 (1,25(OH)2D) of 200 000 IU/month, intramuscular, for 3 months; 17 of them were diagnosed with Graves’ ophthalmopathy.
Patients were followed up over a 3-month duration.
Informed consent was obtained from all participants. The study was conducted in accordance with the stipulations of the Local Ethics and Scientific Committees of Ain Shams University, and the procedures respected the ethical standards in Helsinki Declaration of 1964. A volume of 5 ml of venous blood was extracted without tourniquet after 8 h of overnight fast. Serum was separated by centrifugation and stored at −70°C until it was used.
All participants were subjected to the following:
- Full medical history was taken with emphasis on hyperthyroid symptoms.
- General clinical examination was performed by measuring blood pressure, pulse, temperature, and BMI
- Measurement of thyroid function tests [thyroid-stimulating hormone (TSH), free T3 (FT3), and free T4 (FT4)], 25 hydroxy vitamin D (25-OHD) level at baseline and after 3 months of management, and total serum calcium and phosphorus was carried out. For TSH, we use immunochemiluminometric assay on the Siemens ADVIA Centaur analyser (ADVIA Centaur; Bayer HealthCare LLC, Diagnostics Division, Tarrytown, New York) . FT3 and FT4 levels were detected by direct equilibrium dialysis, high-pressure liquid chromatography, and tandem mass spectrometry . 25-OHD level was determined by a solid-phase enzyme-linked immunosorbent assay, based on the principle of competitive binding . Vitamin D deficiency was defined as a serum level of 25-OHD of less than or equal to 20 ng/ml, vitamin D insufficiency was defined as a serum level between more than 20 ng/ml and less than 30 ng/ml, and normalvitamin D deficiency as more than or equal to 30 ng/ml .
- Neck U/S to measure baseline thyroid volume and monthly for 3 months longitudinal and transverse scans are performed to measure the depth (D), the width (W), and the length (L) of each lobe. The volume of the lobe is calculated by the formula V (ml)=0.479×D×W×L (cm). The thyroid volume is the sum of the volumes of both lobes. The volume of the isthmus is not included. The limits of normal thyroid volume (excluding isthmus, unless its thickness is>3 mm) are 10–15 ml for female and 12–18 ml for male .
- Thyroid scan was performed for patients with no exophthalmos to differentiate it from thyroiditis for newly diagnosed patients
- Ophthalmological examination was performed at baseline and monthly for 3 months using Hertl’s exophthalmometer (Good-Lite 1155 Jansen Farm Dr. Elgin, IL, USA) to assess changes in the severity of ophthalmopathy.
Patients with chronic kidney disease, chronic liver diseases, and other endocrinological diseases such as vitamin D supplementation or any drugs affecting vitamin D level, such as steroids, antiepileptics, methotrexate, INH (isoniazid), thiazides, antacids, calcium channel blockers, and anticonvulsants, were excluded.
Data were analyzed using SPSS [ver. 18; IBM Incorporation; 1111 International Business Machines Corp. (New Orchard Road Armonk, New York)]. Numerical data were tested for normality with D’Agostino–Pearson test; normally distributed data were presented as mean±SD, and non-normally distributed data were presented as median (interquartile range). Categorical data were presented as number and percent of total. Comparative analysis of numerical data was performed with unpaired Student’s t-test or Mann–Whitney test depending on the normality of data. Comparative analysis of categorical data was done with χ2-test. Comparison of paired data was done with paired sample t-test and Wilcoxon’s signed-rank test for parametric and nonparametric data, respectively. Data were tabulated and graphically illustrated. To evaluate the effect of vitamin D supplementation, the groups were compared regarding the degree of change of each parameter, which was calculated from the following formula:
| Results|| |
Comparison between the studied groups regarding baseline demographic, clinical, and laboratory data was done; it showed no significant difference except for TSH, which is significantly lower in group 2 ([Table 1]). In addition, we found hypovitaminosis D in all participants, with a percentage of vitamin D deficiency (vitamin D level: <20 ng/ml) of 73.9% in male and 54.1% in female and percentage of vitamin D insufficiency (vitamin D level: 20–29 ng/ml) of 26.1% in male and 45.9% in female ([Table 2]). On comparing group 1 (on MMI only) with group 2 (on vitamin D and MMI) as regards the percentage of Graves’ ophthalmopathy, our results revealed that 10 (50%) patients of group 1 had Graves’ ophthalmopathy, in comparison with 17 (42.5%) patients in group 2, and thus the percentage of Graves’ ophthalmopathy in our study was 45% (27 patients of a total of 60) ([Table 3]).
|Table 1 Comparison between group 1 and group 2 as regards baseline demographic, clinical, and laboratory data|
Click here to view
|Table 2 Comparison between study groups as regard the percentage of hypovitaminosis D in relation to sex|
Click here to view
|Table 3 Comparison between study groups as regards percentage of Graves’ ophthalmopathy and associated hypovitaminosis D|
Click here to view
On comparing group 1(on MMI) with group 2 (on vitamin D and MMI) as regards the vitamin D status among patients with Graves’ ophthalmopathy, our results revealed that eight (80%) patients with Graves’ ophthalmopathy in group 1 had vitamin D deficiency, whereas the remaining two (20%) had vitamin D insufficiency in comparison with 16 (94.1%) patients in Group 2 (n=17) with vitamin D deficiency and one (5.9%) patient with vitamin D insufficiency; therefore, the percentage of vitamin D deficiency among Graves’ ophthalmopathy patients in our study was 88.9% (24 patients of 27) in comparison with 51.5% (17 patients of 33) in those with no eye signs, whereas the percentage of vitamin D insufficiency was 11.1% (three patients of 27) in comparison with 48.5% (16 patients of 33) in those with no eye signs ([Table 3]).
On correlating baseline vitamin D level with other measured parameters, it showed a significant negative correlation with thyroid volume (r=−0.777, P=0.000) and degree of exophthalmos in both eyes of both study groups (r=−0.752, P=0.000 for the right eye and r=−0.763, P=0.000 for the left eye), whereas a nonsignificant correlation was found with other parameters ([Table 4]).
|Table 4 Correlation between baseline vitamin D level and different parameters|
Click here to view
Patients were followed up after 3 months of management with MMI for group 1 and MMI and vitamin D for group 2. Our results stated changes in clinical and laboratory data (thyroid function test, thyroid volume, exophthalmos, and vitamin D level) in both groups ([Table 5]). Details of the 3-month changes in thyroid function test, thyroid volume, and exophthalmos are illustrated in [Table 6] and [Table 7], as FT3 showed borderline significant reduction from baseline to second month P-value=0.054, but insignificant reduction from the second month to the third month; FT4 showed borderline significant reduction from baseline to second month and significant reduction from the second month to the third month in group 2 compared with group 1. As regards changes in thyroid volume after vitamin D supplementation, there was a highly significant reduction from the baseline to second month and significant reduction from the second month to the third month in group 2 compared with group 1. Moreover, there was a highly significant reduction of exophthalmos from baseline to second month and significant reduction from the second month to the third month in group 2 compared with group 1.
|Table 5 Comparison between group 1 and group 2 as regards thyroid profile, thyroid volume, exophthalmos, and vitamin D level after 3 months|
Click here to view
|Table 6 Comparison between study groups as regards the degree of change of TFT and thyroid volume|
Click here to view
|Table 7 Comparison between study groups as regard the degree of change of exophthalmos|
Click here to view
| Discussion|| |
Our study confirms that 100% of our patients have hypovitaminosis D, as the percentage of vitamin D deficiency was 61.7% (37 patients out of 60) and vitamin D insufficiency was 38.3% (23 patients out of 60), with a mean baseline vitamin D level of 16.7±5.2 ng/ml in group 1 and 15.2±6.2 ng/ml in group 2. These results are in line with the results of those who stated that there is a link between vitamin D status and AITD ,,,,,,,,,, and inconsistent with researches who found higher prevalence of vitamin D deficiency in non-AITD  and others reporting that early stages of thyroid autoimmunity are not associated with low vitamin D levels .
As regard Graves’ ophthalmopathy, our study showed that the percentage of vitamin D deficiency in patients with Graves’ ophthalmopathy was 88.9% compared with those without eye signs − 51.5% − which is in line with studies that reported that the prevalence of vitamin D deficiency in patients with Graves’ ophthalmopathy was 100 versus 66.7% in those without eye signs .
Our results are also in line with researchers who found that hypovitaminosis D is significantly associated with ophthalmopathy in patients with Graves’ hyperthyroidism (61% of patients with GD who were vitamin D deficient and 75% of those who were vitamin D insufficient had ophthalmopathy) but not Hashimoto’s thyroiditis, which suggests that the pathogenesis of the eye changes in the two disorders may be different .
On correlating vitamin D levels with the clinical variables in the study groups, we found an insignificant inverse correlation between vitamin D levels and age (r=−0.121, P=0.359), which is agreement with some previous studies ,,,,,,,,, and in disagreement with those who found that 25-OHD levels were significantly lower in the elderly patients compared with young adults ,, which could be explained by diminished cutaneous production of vitamin D with aging, and/or lower sun exposure . Our results could be explained by the limited age group of our study between 20 and 40 years. On correlating vitamin D levels with BMI of our study groups, we also found no significant correlation (r=0.031, P=0.812), which could also be explained by their low BMI owing to the negative effect of thyrotoxicosis on weight; this is in agreement with studies that declare no significant correlation between vitamin D level and BMI (r=0.064, P=0.307) . In addition, these results are inconsistent with those who stated that obese patients had significantly lower basal 25-OHD concentrations than did age-matched control, and this could be possibly due to increased sequestration of the vitamin into subcutaneous adipose tissue ,.
As regards sex, we found that the percentage of vitamin D deficiency among male patients with GD was higher than that in female patients (74 vs. 54%), antagonizing some studies ,,. These findings may be because of differences in adiposity between male and female with the same BMI, as male have 10–15% less fat content than female .
As regards smoking as a risk factor for Graves’ ophthalmopathy, our study revealed that the percentage of ophthalmopathy among smokers with Graves’ hyperthyroidism was 71.4% and they were also vitamin D deficient, which is in line with studies that proved that more smokers than nonsmokers develop Graves’ ophthalmopathy and smoking can be considered an independent risk factor for GD ,.
As regards thyroid function, we found insignificant positive correlation of baseline TSH level and baseline vitamin D level, and we also found significantly higher levels of TSH by the end of the third month in group 2, which is in agreement with many researchers ,,,,,,,,,,,,,,. In addition, this is inconsistent with the results of others who clarified that TSH level inversely correlated with vitamin D and suggest a significant association between hypovitaminosis D and hypothyroidism ,.
Moreover, we found an insignificant negative correlation of baseline FT3, FT4, and baseline vitamin D levels with a significant decrease in their levels over the end of 3 months in group 2, and this is supported by studies that proved improvement in thyroid hormones after MMI and vitamin D supplementation .
As regards the thyroid volume, our study revealed a significant inverse correlation between baseline vitamin D level and baseline thyroid volume (r=−0.777, P=0.000), which goes in line with other studies .
Furthermore, we noticed a highly significant reduction in thyroid volume during the course of follow-up in both groups. The degree of this reduction was found to be more in group 2 who received MMI and vitamin D supplementation, with a highly significant difference from the baseline to the second month (P<0.001) and a significant difference from the second month to the third month.
To our knowledge, so far no other practical trials were done to evaluate the effect of vitamin D supplementation on thyroid volume.
Regarding exophthalmos, we found an inverse correlation with baseline vitamin D level in the right eye (r=−0.752, P=0.000) and left eye (r=−0.763, P=0.000), which is consistent with researchers who stated the same findings . In addition, we noticed significant reduction in exophthalmos in both eyes of group 1 and highly significant reduction in both eyes of group 2. The degree of this reduction is obviously noted in group 2 with a highly significant difference from the baseline to the second month (P<0.001) and significant difference from the second month to the third month in both eyes.
| Conclusion|| |
In GD, vitamin D supplementation in addition to MMI improve thyroid function test, thyroid volume, and degree of ophthalmopathy in patients with hypovitaminosis D.
Further studies are needed to evaluate the effect of vitamin D supplementation in GD patients with sufficient vitamin D, as well as trials of different formulations to find out the most effective supplementary dose.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Adams JS, Hewison M. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab 2008; 4:80–90.
Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol 2010; 10:482–496.
Menconi F, Marcocci C, Marino M. Diagnosis and classification of Graves’ disease. Autoimmun Rev 2014; 13:398–402.
Jyotsna VP, Sahoo A, Ksh SA, Sreenivas V., Gupta N. Bone mineral density in patients of Graves’ disease pre- & post-treatment in a predominantly vitamin D deficient population. Indian J Med Res 2012; 135:36–41.
] [Full text]
Li Y-B, Xue X-H, Liu S-W, Xi G-X, Zhao L-X, Zhang X-L. Clinical research of serum vitamin D in early Graves’ disease. Chin Rem Clin 2014; 14:242–243.
Liu X-H. Correlation between serum level of 25-(OH)D3
and humoral immunity in patients with autoimmune thyroid diseases [Master’s thesis]. Zhengzhou, China: Zhengzhou University; 2012.
Miao W, Ma J, Guo R, Wang Y-J, Wang G, Guan H-X. Research about the correlation between serum 25(OH)D with Graves’ disease. Chin J Pract Intern Med 2013; 33:394–395.
Wang Y-C. Analysis of the relationship between 25(OH)D, IGF-1 and bone metabolism in patients with Graves’ Disease [Master’s thesis]. Hefei, China: Anhui Medical University; 2014.
Wang Z-S, Song Q-H, Wu Y-P, Chen H, Tan L-L, Sun S-H. Changes of biochemical markers of bone turnover in patients with Graves’ disease. Tianjin Med J 2014; 42:683–686.
Xuan L-Y. The study on the relation between vitamin D and sFas in patients with autoimmune thyroid diseases [Master’s thesis]. Nanchang, China: Nanchang University; 2014.
Yasuda T, Okamoto Y, Hamada N, Miyashita K, Takahara M, Sakamoto F et al.
Serum vitamin D levels are decreased in patients without remission of Graves’ disease. Endocrine 2013; 43:230–232.
Zhang H, Liang L, Xie Z. Low vitamin D status is associated with increased thyrotropin-receptor antibody titer in Graves’ disease. Endocr Pract 2015; 21:258–263.
Kang D-H, Wang Y, Cao W, Wang P, Zhang H-M. Higher prevalence of vitamin D deficiency in female patients with Graves’ disease. Acta Nutr Sin 2013; 25:299–301.
Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Danko K et al.
Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol 2011; 8:243–247.
Yamashita H, Noguchi S, Takatsu K, Koike E, Murakami T, Watanabe S et al.
High prevalence of vitamin D deficiency in Japanese female patients with Graves’ disease. Endocr J 2001; 58:63–69.
Yasuda T, Okamoto Y, Hamada N, Miyashita K, Takahara M, Sakamoto F et al.
Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves’ disease. Endocrine 2012; 42:739–741.
Feng M, Li H, Chen SF, Li WF, Zhang FB. Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine 2013; 43:318–326.
Meyerovitch J, Rotman-Pikielny P, Sherf M, Battat E, Surks MI et al.
Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians. Arch Intern Med 2007; 167:1533–1538.
Yue B, Rockwood AL, Sandrock T et al.
Free thyroid hormones in serum by equilibrium dialysis and online solid-phase extraction-liquid chromatography/tandem mass spectrometry. Clin Chem 2008; 54:642–651.
Scharla SH. Prevalence of subclinical vitamin D deficiency in different European countries. Osteoporos Int 1998; 8(Suppl 2):S7–S12.
Sadat-Ali M, AlElq A, Al-Turki H, Al-Mulhim F, Al-Ali A. Vitamin D level in healthy men in eastern Saudi Arabia. Ann Saudi Med 2009; 29:378–382.
Chaudhary V, Bano S. Thyroid ultrasound. Indian J Endocrinol Metab 2013; 17:219–227.
Sheriba N, Abu Shady MM, Abdelsalam MM, Eliwa TF. Vitamin D levels in Graves’ disease with and without exophthalmos: a case control study. Endocr Abstr 2016; 41:EP1004.
Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V, Tomar N et al.
Prevalence of vitamin D deficiency and its relationships with thyroid autoimmunity in Asian Indians: a community-based survey. Br J Nutr 2009; 102:382–386.
Lahooti H, Wise B, Tjiang H, Champion B, Wall J. Vitamin D deficiency may be a risk factor for ophthalmopathy in patients with Graves’ hyperthyroidism but not Hashimoto’s thyroiditis. Ophthalmol Res 2014; 2:10–17.
Effraimidis G, Badenhoop K, Tijssen JG, Wiersinga WM. Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur J Endocrinol 2012; 167:43–48.
Arabi A, Baddoura R, El-Rassi R, El-Hajj Fuleihan G. XXXXX. J Bone 2010; 47:408–412.
Vieth R, Ladak Y, Walsh PG. Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. J Clin Endocrinol Metab 2003; 88:185–191.
Mac Laughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3
. J Clin Invest 1985; 76:1536–1538.
Nasri H, Baradaran A, Behradmanesh S. Association of body mass index and serum vitamin D level in healthy Iranian adolescents. Endokrynol Pol 2012; 63:29–33.
Saneei P, Salehi-Abargouei A, Esmaillzadeh A. Serum 25-hydroxy vitamin D levels in relation to body mass index: a systematic review and meta-analysis. Obes Rev 2013; 14:393–404.
Abou-Samra A, Valiña-Tóth AL, Lai Z, Yoo W, Gadegbeku CA, Flack JM. Relationship of vitamin D and parathyroid hormone to obesity and body composition in African Americans. Clin Endocrinol (Oxf) 2010; 72:595–603.
Atli T, Gullu S, Uysal AR, Erdogan G. The prevalence of vitamin D deficiency and effects of ultraviolet light on Vitamin D levels in elderly Turkish population. Arch Gerontol Geriatr 2005; 40:53–60.
Gallagher D, Heymsfield SB, Heo M, Jebb SA, Murgatroyd PR, Sakamoto Y. Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index. Am J Clin Nutr 2000; 72:694–701.
Winsa B, Mandahl A, Karlsson FA. Graves’ disease. Endocrine ophthalmopathy and smoking. Acta Endocrinol (Copenh) 1993; 128:156–160.
Bertelsen JB, Hegedus L. Cigarette smoking and the thyroid. Thyroid 1994; 4:327–331.
Fukawa E, Kawakami-Tani T, Tanaka H, Abe Y, Makino I. Effect of 1α-hydroxy vitamin D3
on serum levels of thyroid hormones in hyperthyroid patients with untreated Graves’ disease. Metabolism 1997; 46:1184–1188.
Mackawy AM, Al-Ayed BM, Al-Rashidi BM. Vitamin D deficiency and its association with thyroid disease. Int J Health Sci (Qassim) 2013; 7:267–275.
Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. High vitamin D status in younger individuals is associated with low circulating thyrotropin. Thyroid 2013; 23:25–30.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]