A commentary on: Vitamin D deficiency in non-autoimmune hypothyroidism; a case-control study

Salma Ahi

Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran

We have recently published an article entitled “Vitamin D deficiency in non-autoimmune hypothyroidism; a case-control study”, investigating the role of vitamin D in Autoimmune hypothyroidism and non-Autoimmune hypothyroidism. Different from previous studies, this study directed comparing vitamin D levels between autoimmune and non-autoimmune hypothyroid patients1; in our knowledge it was the first study emphasizing the Vitamin D association in the non-autoimmune form of the disease, having a large-scale study design, reusing a separate control group for comparison of autoimmune and non-autoimmune hypothyroid subjects2. The association of vitamin D deficiency with autoimmune diseases has been well studied3-16; although the association of vitamin D in thyroid autoimmune diseases was obviously reflected in previous studies, the role of vitamin D in non-autoimmune thyroid diseases, negative antibodies hypothyroidism and hyperthyroidism, is unclear.

Our previous case-control study focused on a total of 1138 participants including new cases and previously diagnosed patients undergoing levothyroxine treatment (n=633), nonimmune hypothyroid patients (n=305), and healthy control subjects (n=200). Significantly higher 25OHD levels of healthy control population than hypothyroid participants regardless of autoimmunity is a key finding in this field that needs more studies to differentiate the cause and mechanism. No significant differences in 25OHD levels that were observed between immune and nonimmune hypothyroid participants also remind other clues of the thyroid and vitamin D relationship aside from autoimmunity. Hence this study findings, new aspects of vitamin D and thyroid disease correlation have been marked that; vitamin D deficiency not only impresses the immune system but also affects the thyroid gland function directly1. Investigation of vitamin D's association in non-autoimmune hypothyroidism is the innovation view of this study and indicates it unique, up to now. Limitations of the study were: various duration of disease in participants, the effect of disease course, and treatment dose in this relation, which should be in mind for future studies.

In the literature review, there were few studies comparing vitamin D levels or status of immune and non-immune hypothyroid patients with controls or versus each other. Christopher et al. study on 50 autoimmune and 50 non-auto-immune subjects indicated a lower level of vitamin D in autoimmune hypothyroid patients17. Our study results demonstrated a considerably lower level of vitamin D in both Hashimoto's immune and non-immune thyroiditis compared with healthy controls (P < 0.05). But there wasn’t any difference between immune and non-immune hypothyroid groups. Christopher et al. didn’t make any comparison with healthy normal subjects. Their vitamin D deficiency cut off criteria were considered below 20 ng/ml as well as our study. But no information was addressed about the season of vitamin D assessment.

The status of vitamin D deficiency was compared between immune and non-immune hypothyroid patients in the study of Shaye Kivity et al.3 they study revealed a higher rate of vitamin D deficiency in immune thyroiditis. The cut off ranged that was considered as the vitamin D deficiency in their study was 10; while we used 20 ng/dl as our cut off. Clinical judgment and comparison of studies according to different definitions of vitamin D deficiency, is difficult. Shaye Kivity et al. was the only study taking healthy control groups into account for comparisons; While their study sample size was very low. Also, they report higher rate of vitamin D deficiency in immune than non-immune hypothyroid patients; in contrary to ours.

Comparison of immune and non-immune hypothyroidism by Jaideep Khare et al. didn't include the control group, so conclusion about the possible role of the vitamin D in non-autoimmune hypothyroidism would not be judicable18. Dong Yeob Shin's study, comparing the same groups of immune and non-immune, hadn't a healthy euthyroid group in study design, too19.

In pathophysiological view, Vitamin D plays a key role in the prevention of inflammatory, infectious and autoimmune diseases by interfering in macrophages-TCD8-TCD4 and B cells function20,21, progression of DM1, SLE, RA and IBD in vitamin D deficiency is considered recently22,23. Also, an increase in the incidence rate of Hashimoto thyroiditis might be related to vitamin D deficiency24, low 25OHD have recently been associated with autoimmune thyroid disorders: Hashimoto thyroiditis, Graves’ disease, and post-partum thyroiditis, as well as thyroid cancer25,26. Limited articles in controversy, declared no relationship between Hashimoto and vitamin D deficiency, despite the significant positive association of TpoAb and vitamin D in males; also none of the studied females, as the most prevalent part of Hashimoto thyroiditis population, is vitamin D deficient27. Around the other article, it's more acceptable to record no association between Hashimoto thyroiditis and vitamin D insufficiency, not deficiency17.

Role of vitamin D deficiency in hypothyroidism aside from cause is a novel challenge, vitamin D role in non-immune thyroid diseases, hasn’t been studied before; the relationship between thyroid autoantibodies and vitamin D, as well as patients’ thyroid status, opens a new door in nowadays practice.

Pub year



Vit D  cut off


Study by


No control euthyroid  group

Lower vit D level in immune cases






With control group but small sample size

A higher rate of vit D deficiency in immune thyroiditis




No control euthyroid  group

Patients with TPOAb positivity have more significant 25(OH)D3 deficiency





Lack of sun exposure, socioeconomic data, no control euthyroid  group


Low serum 25(OH)D is related to the presence of TgAb in females



Wang x


No control euthyroid  group

Vit D level is affecting the presence of TPOAb in AITDs

9.3ng/ml RIA



None of female participants are vitamin d deficient

No relationship between Hashimoto and vit D deficiency





No control euthyroid  group, but vitamin D sufficient control

Vitamin D deficiency was significantly associated with AT in the elderly





No control euthyroid  group

Vitamin D deficiency is associated with HT in children and adolescents





No control euthyroid  group

Vitamin D insufficiency was associated with AITD and HT, especially overt hypothyroidism



  1. Ahi S, Dehdar MR, Hatami N. Vitamin D deficiency in non-autoimmune hypothyroidism: a case-control study. BMC endocrine disorders. 2020 Dec; 20(1): 1-6.
  2. Sun W, Joffe MM, Chen J, et al. Design and analysis of multiple events case–control studies. Biometrics. 2010 Dec; 66(4): 1220-9.
  3. Kivity S, Agmon-Levin N, Zisappl M, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011; 8: 243–247.
  4. Tamer G, Arik S,Tamer I, et al. Relative vitamin D insufficiency in Hashimoto’s thyroiditis. Thyroid. 2011; 21: 891–896.
  5. Bozkurt NC, Karbek B, Ucan B, et al. The association between severity of vitamin D deficiency and Hashimoto’s thyroiditis. Endocr Pract. 2013; 19: 479–484.
  6. Mansournia N, Mansournia MA, Saeedi S, et al. The association between serum 25OHD levels and hypothyroid Hashimoto’s thyroiditis. J Endocrinol Investig. 2014; 37: 473–476.
  7. Shin DY, Kim KJ, Kim D, et al. Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J. 2014; 55: 476–481.
  8. Unal AD, Tarcin O, Parildar H, et al. Vitamin D deficiency is related to thyroid antibodies in autoimmune thyroiditis. Cent Eur J Immunol. 2014; 39: 493–497.
  9. Choi YM, Kim WG, Kim TY, et al. Low levels of serum vitamin D3 are associated with autoimmune thyroid disease in pre-menopausal women. Thyroid. 2014; 24: 655–661.
  10. Wang X, Zynat J, Guo Y, et al. Low serum vitamin D is associated with anti-thyroid-globulin antibody in female individuals. Int J Endocrinol. 2015; 2015: 285290.
  11. Kim D. Low vitamin D status is associated with hypothyroid Hashimoto’s thyroiditis. Hormones. 2016; 15: 385–393.
  12. Wang J, Lv S, Chen G, et al. Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrients. 2015; 7: 2485–2498.
  13. Muscogiuri, Mari D, Prolo S, et al. 25 Hydroxyvitamin D deficiency and its relationship to autoimmune thyroid disease in the elderly. Int J Environ Res. Public Health. 2016; 13: E850.
  14. Camurdan OM, Döğer E, Bideci A, et al. Vitamin D status in children with Hashimoto thyroiditis. J Pediatr Endocrinol Metab. 2012; 25: 467–470.
  15. Evliyaoğlu O, Acar M, Özcabı B, et al. Vitamin D deficiency and Hashimoto’s thyroiditis in children and adolescents: A critical vitamin D level for this association? J Clin Res Pediatr Endocrinol. 2015; 7: 128–133.
  16. Metwalley KA, Farghaly HS, Sherief T, et al. Vitamin D status in children and adolescents with autoimmune thyroiditis. J Endocrinol Investig. 2016; 39:793–797.
  17. Christopher S, Santhanavally RN. Study on Association between Vitamin D Deficiency and Autoimmune Hypothyroidism. Population. JMSCR. 2019; 07(11)258-265, November.
  18. Khare J, Reddy B, Nalla S, et al. Vitamin D deficiency and its association with thyroid peroxidase antibodies positive hypothyroidism-Experience in a tertiary center in South India. Medical Journal of Dr. DY Patil University. 2017 Jul 1; 10(4): 355.
  19. Shin DY, Kim KJ, Kim D, et al. Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei medical journal. 2014 Mar 1; 55(2): 476-81.
  20. Kulie T, Groff A, Redmer J, et al. Vitamin D: an evidence-based review. The Journal of the American Board of Family Medicine. 2009 Nov 1; 22(6): 698-706.
  21. Dankers W, Colin EM, van Hamburg JP, et al. Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Frontiers in immunology. 2017 Jan 20; 7: 697.
  22. Kamen DL, Cooper GS, Bouali H, et al. Vitamin D deficiency in systemic lupus erythematosus. Autoimmunity reviews. 2006 Feb 28; 5(2): 114-7.
  23. Deluca HF, Cantorna MT. Vitamin D: its role and uses in immunology. The FASEB Journal. 2001 Dec 1; 15(14): 2579-85.
  24. Clinckspoor I, Gérard AC, Van Sande J, et al. The vitamin D receptor in thyroid development and function. European thyroid journal. 2012; 1(3): 168-75.
  25. Muscogiuri G, Tirabassi G, Bizzaro G, et al. Vitamin D and thyroid disease: To D or not to D?Eur J Clin Nutr.2015; 69: 291–296.
  26. Kim D. The role of vitamin D in thyroid diseases.Int J Mol Sci. 2017; 18: 1949.
  27. Yasmeh J, Farpour F, Rizzo V, et al. Hashimoto thyroiditis not associated with vitamin D deficiency. Endocrine Practice. 2016 Jul; 22(7): 809-13.

Article Info

Article Notes

  • Published on: December 14, 2020


  • Vitamin D
  • Hypothyroidism


*Dr. Salma Ahi
Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran
Email: salmaahi.61@gmail.com.