Effect of low and high doses of vitamin D3 therapy on vitamin D3, antithyroid antibody and thyroid hormone levels in thyroid autoimmunity: Research Article

Ildikó Molnár

doi:10.58372/2835-6276.1153

Authors

Ildikó Molnár

DOI:

https://doi.org/10.58372/2835-6276.1153

Keywords:

vitamin D3 status, low and high doses of vitamin D3, autoimmune thyroid diseases, efficacy of vitamin D3 therapy

Abstract

Aims: Vitamin D₃ deficiency is more common in autoimmune thyroid diseases (AITD). Vitamin D₃ supplementation in AITD is not questioned, but the required doses have been offered differently in several reports. This study attempts to provide a clinical answer as to what doses of vitamin D₃ may be effective in AITD.

Methods: Ninety-seven patients were included in the study: 44 with Hashimoto’s thyroiditis (HT), 26 with Graves ’disease (GD) and 27 controls. Serum vitamin D₃, thyroid hormone and autoantibody levels against thyroid peroxidase (TPO) and TSH receptor were measured before and after treatment. Biochemical data were measured by a fully automated competitive chemiluminescence assay and presented as geometric mean(95% confidence interval).

Results: Baseline vitamin D₃ deficiency was detected in 22 out of 44 HT, 13 out of 26 GD and 19 out of 27 controls, and improved after vitamin D₃ therapy. Vitamin D₃ therapy significantly increased serum vitamin D₃ levels in all patient groups [46.07(16.55-128.29) vs. 71.05(40.61-124.3) nmol/l, p<0.0001 for HT, 44.27(8.98-218.25) vs. 64.22(38.85-106.16) nmol/l, p<0.0207 for GD, and 39(15.57-97.73) vs. 59.32(27.27-129.03) nmol/l, p<0.0003 for controls]. The increass in vitamin D₃ levels was found after low-dose vitamin D₃ therapy (<7000 NE/week) in HT (p<0.0001) and controls (p<0.0002), but not in GD. The success of vitamin D₃ therapy was dependent on high doses of vitamin D₃ (>7000 NE/week) in GD, but levels were lower in Graves’ ophthalmopathy (p<0.0302). Anti-TPO antibody and TSH levels were decreased by low doses of vitamin D₃ in HT, but FT₄ and FT₃ decreased, and TSH levels increased only by high doses in GD.

Conclusion: The efficacy of vitamin D₃ therapy was demonstrated in all patient groups. The greatest improvement in vitamin D₃ status was seen in HT. A dose-dependency of vitamin D₃ therapy was rather related to the improvement in GD.

References

MUSCOGIUIRI G, MARI D, PROLO S, ET AL. 25 HYDROXYVITAMIN D DEFICIENCY AND ITS RELATIONSHIP TO AUTOIMMUNE THYROID DISEASE IN ELDERLY. INT J ENVIRON RES PUBLIC HEALTH. 2016; 13: 850-856.

VONDRA K, STÁRKA L, HAMPL R. VITAMIN D AND THYROID DISEASES. PHYSIOL RES. 2015; 64(SUPPL 21): S95-S100.

SHIN DY, KIM KJ, KIM D, HWANG S, LEE EJ. LOW SERUM VITAMIN D IS ASSOCIATED WITH ANTI-THYROID PEROXIDASE ANTIBODY IN AUTOIMMUNE THYROIDITIS. YONSEI MED J. 2014; 55: 476-481.

ALJABRI KS, ALNASSER IM, BOKHARI SA, ET AL. VITAMIN D DEFICIENCY IS RELATED TO THYROID ANTIBODIES AMONG TYPE 2 DIABETIC MELLITUS PATIENTS. TRENDS DIAB METAB. 2019 ;2: 1-5.

CHOI YM, KIM WG, KIM TY, ET AL. LOW LEVELS OF SERUM VITAMIN D3 ARE ASSOCIATED WITH AUTOIMMUNE THYROID DISEASE IN PREMENOPAUSAL WOMEN. THYROID. 2014 ;24: 655-661.

MANGARAJ S, CHOUDHURY AK, SWAIN BM, SARANGI PK, MOHANTY BK, BALIARSINHA AK. EVALUATION OF VITAMIN D STATUS AND ITS IMPACT ON THYROID RELATED PARAMETERS IN NEW ONSET GRAVES’ DISEASE – A CROSS-SECTIONAL OBSERVATIONAL STUDY. IND J ENDOCRINOL METAB. 2019; 23: 35-39.

AHN HY, CHUNG YJ, CHO BY. SERUM 25-HYDROXYVITAMIN D MIGHT BE AND INDEPENDENT PROGNOSTIC FACTOR FOR GRAVES’ DISEASE RECURRENCE. MEDICINE. 2017; 96: 31-35.

KE W, SUN T, ZHANG Y, ET AL. 25-HYDROXYVITAMIN D SERUM LEVEL IN HASHIMOTO’S THYROIDITIS, BUT NOT GRAVES’ DISEASE IS RELATIVELY DEFICIENT. ENDOCRINE J. 2017; 64: 581-587.

DI ROSA M, MALAGUARNERA M, NICOLETTI F, MALAGUARNERA L. VITAMIN D3: A HELPFUL IMMUNO-MODULATOR. IMMUNOLOGY. 2011; 134: 123-139.

LIU W, ZJANG L, XU HJ, ET AL. THE ANTI-INFLAMMATORY EFFECTS OF VITAMIN D IN TUMORGENESIS. INT J MOL SCI. 2018; 19: 2736-2751.

SASSI F, TAMONE C, D’AMELIO P. VITAMIN D: NUTRIENT, HORMONE, AND IMMUNOMODULATOR. NUTRIENTS. 2018; 10: 1656-1669.

WIMALAWANSA SJ. ASSOCIATIONS OF VITAMIN D WITH INSULIN RESISTANCE, OBESITY, TYPE 2 DIABETES, AND METABOLIC SYNDROME. J STEROID BIOCHEM MOL BIOL. 2018; 175: 177-189.

BELLAN M, ANDREOLI L, MELE C, ET AL. PATHOPHYSIOLOGICAL ROLE AND THERAPEUTIC IMPLICATIONS OF VITAMIN D IN AUTOIMMUNITY: FOCUS ON CHRONIC AUTOIMMUNE DISEASES. NUTRIENTS. 2020; 12: 789-818.

MUSCOGIUIRI G, MITRI J, MATHIEU C, ET AL. VITAMIN D AS A POTENTIAL CONTRIBUTOR IN ENDOCRINE HEALTH AND DISEASE. EUR J ENDOCRINOL. 2014; 171: R101-R110.

KIM D. LOW VITAMIN D STATUS IS ASSOCIATED WITH HYPOTHYROID HASHIMOTO’S THYROIDITIS. HORMONES. 2016; 15: 385-393.

TALAEI A, GHORBANI F, ASEMI Z. THE EFFECTS OF VITAMIN D SUPPLEMENTATION ON THYROID FUNCTION IN HYPOTHYROID PATIENTS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL. INDJENDOCRINOL METAB. 2018; 22: 584-588.

AMREIN K, SCHERKL M, HOFFMANN M, ET AL. VITAMIN D DEFICIENCY 2.0: AN UPDATE ON THE CURRENT STATUS WORLDWIDE. EUR J CLIN NUTR. 2020 ;74 :1498-1513.

WERNER SC. MODIFICATION OF CLASSIFICATION OF EYE CHANGES OF GRAVES’ DISEASE: RECOMMENDATIONS OF THE AD HOC COMMITTEE OF AMERICAN THYROID ASSOCIATION. J CLIN ENDOCRINOL METAB. 1977; 44: 2034.

MOURITS MP, PRUMMEL MF, WIERSINGA WM, ET AL. CLINICAL ACTIVITY SCORE AS A GUIDE IN THE MANAGEMENT OF PATIENTS WITH GRAVES’ OPHTHALMOPATHY. CLIN ENDOCRINOL (OXF). 1997; 47: 1409-1417.

SZODORAY P, NAKKEN B, GAAL J, JONSSON R, SZEGEDI A, ET AL. THE COMPLEX ROLE OF VITAMIN D IN AUTOIMMUNE DISEASES. SCAND J IMMUNOL . 2008; 68: 261-269.

KIVITY S, AGMON-LEVIN N, ZISAPPI M, ET AL. VITAMIN D AND AUTOIMMUNE THYROID DISEASES. CELL MOL IMMUNOL. 2011; 8: 243-247.

BIZZARO G, SHOENFELD Y. VITAMIN D AND THYROID AUTOIMMUNE DISEASES THE KNOWN AND THE OBSCURE. IMMUNOL RES. 2015; 61: 107-109.

EL-HANBULI HM, DAWOUD NM, MAHMOUD RH. NARROW-BAND UVB EFFECTS ON CUTANEOUS VITAMIN D RECEPTOR EXPRESSION AND SERUM 25-HYDROXYVITAMIN D IN GERERALIZED VITILIGO. PHOTO-DERMATOL PHOTOIMMUNOL PHOTOMED. 2018; 34: 175-183.

BOTELHO IMB, NETO AM, SILVA CA, ET AL. VITAMIN D IN HASHIMOTO’S THYROIDITIS AND ITS RELATIONSHIP WITH THYROID FUNCTION AND INFLAMATORY STATUS. ENDOCRINE J. 2018; 65: 1029-1037.

SULEJMANOVIC M, JAKUBOVIC-CICKUSIC A, BEGIC A, ET AL. THE RELATIONSHIP BETWEEN THYROID AUTOANTIBODIES AND VITAMIN D LEVELS IN PRIMARY HYPOTHYROIDISM. MEDARCH. 2020; 74-5: 359-362.

LEKO MB, JUREŠKO I, ROZIĆ I, ET AL. VITAMIN D AND THE THYROID: A CRITICAL TEVIEW OF THE CURRENT EVIDENCE. INT J MOL SCI. 2023; 24: 3586-3602.

MACIEJEWSKI A, KOWALCZYK MJ, GASIŃSKA T, ET AL. THE ROLE OF VITAMIN D RECEPTOR GENE POLYMORPHISMS IN THYROID-ASSOCIATED ORBITOPATHY. OCUL IMMUNOL INFLAMM. 2019; 19: 1-8.

TARASHVILI N, JAVASHVILI L, GIORGADZE E. VITAMIN D DEFICIENCY IS MORE COMMON IN WOMEN WITH AUTOIMMUNE THYROIDITIS: A RETROSPECTIVE STUDY. INT J ENDOCRINOL. HTTPS://WWW.NCBI.NLM. NIH.GOV/PMC/ARTICLES/PMC8387174/; DOI.ORG//10.1155/2021/4465563.

SIMSEK Y, CAKIR I, YETMIS M, ET AL. EFFECTS OF VITAMIN D TREATMENT ON THYROID AUTOIMMUNITY. J RES MED SCI. 2016; 21: 92-97.

ANARAKI PV, AMINORROAYA A, AMINI M, ET AL. EFFECT OF VITAMIN D DEFICIENCY TREATMENT ON THYROID FUNCTION AND AUTOIMMUNITY MARKERS IN HASHIMOTO’S THYROIDITIS: A DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED CLINICAL TRIAL. J RES MED SCI. 2017; 22: 103-108.

CHAUDHARY S, DUTTA D, KUMAR M, ET AL. VITAMIN D SUPPLEMENTATION REDUCES THYROID PEROXIDASE ANTIBODY LEVELS IN PATIENTS WITH AUTOIMMUNE THYROID DISEASE: AN OPEN-LABELED RANDOMIZED CONTROLLED TRIAL. IND J ENDOCRINOL METAB. 2016; 20: 391-398.

CHAHARDOLL R, SABOOR-YARAGHI AA, AMOUZEGAR A, KHALILLI D, VAKILI AZ, AZIZI F. CAN SUPPLEMENTATION WITH VITAMIN D MODIFY THYROID AUTOANTIBODIES (ANTI-TPO AB, ANTI-TG AB) AND THYROID PROFILE (T3, T4, TSH) IN HASHIMOTO’S THYROIDITIS? A DOUBLE BLIND, RANDOMIZED CLINICAL TRIAL. HORM METAB RES. 2019; 51: 296-301.

GALUŞCA D, POPOVICIU MS, BABEŞ EE, ET AL. VITAMIN D IMPLICATIONS AND EFFECT OF SUPPLEMENTATION IN ENDOCRINE DISORDERS: AUTOIMMUNE THYROID DISORDERS (HASHIMOTO’S DISEASE AND GRAVES’ DISEASE), DIABETES MELLITUS AND OBESITY. MEDICINA. 2022; 58: 1-15.

MANSOURNIA N, MANSOURNI MA,SAEEDI S, DEHGHAN J. THE ASSOCIATION BETWEEN SERUM 25OHD LEVELS AN HYPOTHYROID HASHIMOTO’S THYROIDITIS. I ENDOCRINOL INVEST. 2014; 37: 473-476.

CHAO G, ZHU Y, FANG L. CORRELATION BETWEEN HASHIMOTO’S THYROIDITIS-RELATED THYROID HORMONE LEVELS AND 25-HYDROXYVITAMIN D. FRONT ENDOCRINOL.HTTPS://WWW.FRONTIERSIN.ORG/JOURNALS/ENDOCRINOLOGY/ARTICLES/10.3389/FENDO.2020.00004/FULL;DOI:10.3389/FENDO.2020.00004.

ZHAO R, ZHANG W, MA C, ET AL. IMMUNOMODULATORY FUNCTION OF VITAMIN D AND ITS ROLE IN AUTOIMMUNE DISEASE. FRONT IMMUNOL. HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ ARTICLES/ PMC7933 459/; DOI:10.3389/FIMMU.2021.574967.

SHERIBA N, ELEWA AA, MAHDY M, EL ET AL. EFFECT OF VITAMIN D3 IN TREATING HYPERTHYROIDISM IN PATIENTS WITH GRAVES’ DISEASE. EGYPT J INTERN MED. 2017; 29: 64-70.

CZARNYWOJTEK A, FLOREK E, PIETROŃCZYK K, ET AL. THE ROLE OF VITAMIN D IN AUTOIMMUNE THYROID DISEASES: A NARRATIVE REVIEW. J CLIN MED. 2023; 12: 1452-1463.

VASSALLE C, PARLANTI A, PINGITORE A, BERTI S,IERVASI G, SABATINO L. VITAMIN D, THYROID HORMONES AND CARDIOVASCULAR RISK: EXPLORING THE COMPONENTS OF THIS NOVEL DISEASE TRIANGLE. FRONT PHYSIOL. HTTPS://WWW.FRONTIERSIN.ORG/JOURNALS/PHYSIOLOGY/ARTICLES/10.3389/FPHYS.2021.72 2912/ FULL; DOI:10.3389/FPHYS.2021.722912.

DUNTAS LH, ALEXANDRAKI KI. ON THE CENTENNIAL OF VITAMIN D – VITAMIN D, INFLAMMATION, AND AUTOIMMUNE THYROIDITIS: A WEB OF LINKS AND IMPLICATIONS. NUTRIENTS. 2022; 14: 5032: 5045.