|Year : 2019 | Volume
| Issue : 9 | Page : 1224-1228
The relationship between 25 hydroxy Vitamin D3 and thyroid antibodies with thyroid benign-malign neoplasms
S Yildiz1, O Ekinci2, R Ucler1
1 Van Yuzuncu Yil University, Department of Endocrinology, Van, Turkey
2 Lice State Hospital, Diyarbakir, Turkey
|Date of Acceptance||23-Apr-2019|
|Date of Web Publication||6-Sep-2019|
Dr. S Yildiz
Van Yuzuncu Yil University, Department of Endocrinology, Van
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: To study the relationship between vitamin D and thyroid antibodies with thyroid benign-malign neoplasms. Materials and Methods: The vitamin D vitamin and thyroid antibodies of 179 patients who underwent thyroidectomy for thyroid nodule were retrospectively reviewed. Results: The mean age of the patients was 44.97 ± 14.139. Vitamin D levels were 14.473 ± 4.9999 ng/ml in women and 19.584 ± 6.1981 ng/ml in men and the mean was 15.016 ± 5.3579 ng/ml. There was a significant relationship between sex and vitamin D level (P < 0, 05). Antithyroglobulin antibody (anti-TGB) had been detected in 95 patients and Antithyroid peroxidase antibody (anti TPO) in 58 patients. There was no significant relationship between vitamin D levels (P: 0, 65), anti-TPO positivity (P: 0, 86), and anti-TGB (P: 0, 12) with benign-malignant neoplasm of thyroid. There was no relationship between vitamin D and metastatic disease (P: 0, 30) as well. In addition, no association was found between malignancy and metastasis (P = 0.068, P = 0.14, P: 0, P = 0, respectively) with thyroid antibody positivity (anti TPO and/or anti TGB) in severe deficiency (<10 ng/ml) and deficiency (<20 ng/ml) of vitamin D. Conclusion: Vitamin D deficiency or thyroid autoantibodies did not have any significant effect on thyroid malignancies or metastatic disease separately or together.
Keywords: Thyroid antibody levels, thyroid neoplasm, vitamin D level
|How to cite this article:|
Yildiz S, Ekinci O, Ucler R. The relationship between 25 hydroxy Vitamin D3 and thyroid antibodies with thyroid benign-malign neoplasms. Niger J Clin Pract 2019;22:1224-8
|How to cite this URL:|
Yildiz S, Ekinci O, Ucler R. The relationship between 25 hydroxy Vitamin D3 and thyroid antibodies with thyroid benign-malign neoplasms. Niger J Clin Pract [serial online] 2019 [cited 2020 Jan 24];22:1224-8. Available from: http://www.njcponline.com/text.asp?2019/22/9/1224/266167
| Introduction|| |
Primary thyroid carcinomas account for 1% of malignant tumors. Differential thyroid carcinoma (DTC) (papillary thyroid carcinoma, follicular thyroid carcinoma) arising from the follicular epithelium is the most common in the thyroid as it is in the endocrine system malignancies. It is responsible for 1.5% of malignancies in women and 0.5% in males. Environmental, genetic, and hormonal factors cause thyroid carcinomas.
Recent studies indicate that one of the environmental impacts may be lack of vitamin D. It is reported that calcitriol diminishes tumor development through effects on cell proliferation, differentiation, apopitosis, metastases, inflammation, invasion, and angiogenesis. Vitamin D nuclear receptors (DVR) are also found in breast, prostate, colon, thyroid carcinoma, and leukemia. Some studies have also proven that high vitamin D levels have protective effects against prostate, breast and colorectal cancers. However, there are conflicting results about the relationship between thyroid cancer and serum vitamin D levels.,,,
It is stated that chronic inflammation may predispose an individual to neoplastic transformation  and autoimmune diseases are associated with several kinds of cancers. There are numerous studies focused on the relationship between antithyroglobulin antibody (antiTG) and antithyroid peroxidase antibody (antiTPO) positivity, which are responsible for autoimmune thyroid diseases, with thyroid carcinoma.,,,,,, In this study, we aimed to investigate the relationship between vitamin D level and thyroid antibodies (TAB) with benign-malign neoplasms separately and together.
| Materials and Method|| |
In this study, we examined 179 patients who had applied to the Endocrinology Clinic of Van Yuzuncu Yil University Medical Faculty Hospital between 01.01.2010 and 15.06.2017 and who had undergone thyroidectomy. Acceptance of ethics was taken from the ethics committee of the same institution. Criteria for patients in the study was determined as follow; no recent history of blood transfusion, the absence of any medication and mineral supplements for treatment, the absence of chronic renal failure, and the existence of previous pathology in patients with completion thyroidectomy.
The age, sex, serum 25(OH) D3, TSH, creatinine, antiTG, anti TPO levels, and pathology results of the cases included in the study were examined retrospectively with the computer system of our hospital. Vitamin D levels were classified as <10 ng/ml, 10–19 ng/ml, 20–29 ng/ml and >30 ng/m, respectively, according to the Endocrine Association.
Blood samples were taken the day before the operation; serum creatine was analyzed by colorimetric test on a Roche/Hitachi Cobas C 501 analyzer, 25 OH vitamin D, AntiTG, antiTPO levels were measured on the ArciHitect 16200-ABBott analyzer and serum TSH levels were measured by chemiluminescence method on a Roche/Hitachi cobas E 601 analyzer.
Descriptive statistics for the features studied are expressed as mean, standard deviation, minimum, and maximum values. Single direction variance analysis was performed to compare group averages in terms of continuous variables. Following the analysis of variance, Duncan's multiple range test was used to identify the different groups. Pearson correlation coefficients were calculated to determine the relationship between these variables. The statistical significance level in the calculations was determined as P < 0.05, SPSS (ver: 21.0) statistical package program was used for the calculations.
| Results|| |
Totally, 179 patients who applied to the Endocrinology clinic of Van Yuzuncu Yil University Medical Faculty (YYU) Hospital for thyroidectomy were included in the study. Of the cases, 160 were female (89.3%) and 19 were male (10.7%). The mean age was 44.3 ± 13.481 years for females and 50.6 ± 18.267 years for males (P: 0.065).
Vitamin D levels; the overall mean was 15.01 ± 5.35. The mean was 14.47 ± 4.99 for females and 19.58 ± 6.19 for males. Vitamin D level was significantly lower in females (P: 0.001) and it was less than 30 ng/ml except for only 2 cases of malignancy in the whole group [Table 1].
|Table 1: Descriptive statistics and comparison results according to gender|
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When we compared anti-TPO or anti-TG positive cases (1,3 ± 1, 22, 4,84-0,00 μU/ml) to non-incident cases (1,16 ± 0,95, 4,5-0,001 μU/ml) TSH was similar (P: 0.36). All the same there was no TSH difference between malign (1,4 ± 0,97, 4,5-0,001 μU/ml) and benign (1,1 ± 1, 3, 7, 2-0,000 μu/ml) pathologies (P: 0, 08).
The cases with positive antiTPO antibody were younger (P: 0.003) and their nodule diameters were smaller (P: 0.001). There was no correlation between vitamin D levels and antiTPO antibodies (P: 0.301). Likewise, there was no correlation between vitamin D levels and antiTG antibodies (P: 0.296) [Table 2].
|Table 2: Relationship between AntiTPO-AntiTG and age, vitamin D, size of nodules|
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In general there were 101 benign diagnoses (Multinodular goiter: 75, Nodular hyperplasia: 7, Graves: 2, Follicular adenoma: 4, Hashimato: 13) and 78 malignant diagnoses (Papillary thyroid carcinoma: 73, Medullary thyroid carcinoma: 2, Follicular thyroid carcinoma: 3) and there was no relation between gender-age and malignancy (P: 0.72, P: 0.922, respectively). There was no relationship between vitamin D and pathological diagnosis as well (P: 0.65). In addition, there was no correlation between TAB positivity and pathology (P: 0.12 for antiTG, P: 0.86 for anti-TPO). Nodule size was larger in benign diagnoses (P: 0.001). There was no relationship between vitamin D level and lymph node metastasis in our study (P: 0.35). There was a positive correlation between tumor size increase and lymph node metastasis (P: 0.007) [Table 3].
|Table 3: Analysis according to the pathology of the cases and the positivity of metastatic lymph nodes|
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Vitamin D levels were categorized as <10 ng/mL, 11–19 ng/mL, 19–29 ng/mL, and ≥30 ng/mL. There was no significant difference between these four groups and pathologic diagnosis (P: 0.45) [Table 4].
|Table 4: Relationship between categorized vitamin D and benign-malignant neoplasm|
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The patients whose vitamin D levels were less than 10 ng/ml and had antiTGB or AntiTPO positivity were compared to those with antibody negatives and there was no difference between malignant (positive: 4/12, 33%) and benign (positive: 6/8, 75%) pathologies (P: 0,068). Likewise, in the group whose 25 OH vitamin D level was below 20 ng/ml, antibody-positive cases were compared to negatives and there was no difference between malign (positive: 17/51, 33,3%) and benign (positive: 19/39, 48,7%) pathologies (P: 0,14). When the same analysis was performed for metastatic disease, metastasis was detected in 1 of 4 antibody-positive patients with 25 OH of D <10 ng/ml and there was no significant difference (P: 0.58) between them and antibody negatives (1/8) in respect to metastases. Besides metastases were detected in 3 out of 17 antibody-positive patients with 25 OH vitamin D levels < 20 ng/ml and there was no significant difference (6/34) between them and antibody negatives with the same vitamin level for metastases (P: 1).
| Discussion|| |
In our retrospective study of thyroidectomy pathologies, we did not find any association between vitamin D levels and benign-malign neoplasm (P: 0.653). There was no difference (P: 0.89) when we graded vitamin D deficiency as <10 ng/ml, 11–19 ng/ml, 20–29 ng/ml and ≥30 ng/ml.
In all cases of benign and malignant except 2 cases (from malignant group) 25 OH vitamin D blood level was below 30 ng/ml, namely it was inadequate or incomplete.
Stepien et al. found low concentrations of calcitriol in papillary, follicular, anaplastic thyroid cancer cases and it was detected at the lowest level in anaplastic thyroid cancers. These levels correlated negatively with cancer stage. Similarly, Kim et al., found a significantly lower D vitamin concentration in patients with PTC with tumor greater than 1 cm or lymph node metastasis. However; we did not find any significant difference between vitamin D level and lymph node metastasis (P: 0.35).
Sahin et al. found vitamin D deficiency (<20 ng/ml) in 71% (166/235) of Papillary Thyroid Cancer (PTC) patients and in 59% (64/108) of the control group and was ineffective for cancer prognosis. We found 25 OH vitamin D levels below 20 ng/ml in 82% of the malignant group and 84% of the benign group.
In Roskies et al.'s study, vitamin D deficiency (<15 ng/mL) was found in 75% (9/12) of the patients with Differentiated Thyroid Carcinoma (DTCC) and 37.5% (33/88) of the patients with thyroid nodule. In our study, vitamin D levels were below 15 ng/ml in 48.7% (38/78) of patients with thyroid malignancy and 48.51% (49/101) of benign pathology.
Laney et al. found that 25(OH) D concentrations below 30 ng/ml were not different in 45 patients with thyroid cancer (TC) in remission, 24 patients with active TC and 42 patients with thyroid nodule. Furthermore, there was no difference between the levels of vitamin D in the thyroid cancer subtypes. Similar to our study, Jonklaas et al. stated that vitamin D levels were not associated with TC diagnosis and the stage of cancer.
The other research topic of our study was thyroid autoantibodies (TAB) and we did not find any association between thyroid autoantibodies (TAB) and thyroid benign-malign neoplasms (P: 0.121 for antiTG, P: 0.863 for anti-TPO). Patients with anti-TGB and/or anti-TPO positivity with vitamin D levels below 10 ng/ml were compared to patients with antibody negative and there was no difference between malignant (positive: 4/12, 33%) and benign (positive: 6/8, 75%) pathologies (P: 0.068). Similarly, in the group with 25 OH vitamin D level below 20 ng/ml, antibody positive cases were compared to negative cases and there was no difference between malign (positive: 17/51, 33.3%) and benign (positive: 19/39, 48.7%) pathologies (P: 0.14).
Metastasis was detected in 1 of 4 antibody-positive patients with 25 OH vitamin D level below 10 ng/ml and there was no statistically significant difference (P: 0.58) between them and antibody negatives with deep vitamin D deficiency (1/8) in respect to metastasis. Once more, metastasis was detected in 3 of 17 antibody-positive patients with 25 OH vitamin D level below 20 ng/ml and there was no statistically significant difference (P: 1) between them and antibody negative patients with the same vitamin level in respect to metastasis (6/34).
A review about Hashimoto's thyroiditis (HT) stated that there was no correlation between HT and PTC according to thyroid needle biopsy results, on the other hand, when after thyroidectomy pathology results were evaluated, the PTC risk was 1.59 and the PTC prevalence was found as 27.56% in patients with HT. Some studies on HT have reported TC associations at up to 30% and it has also been reported that high TSH might be a risk factor for TC. There was no TSH difference between the groups in our study and no effect of antibodies on the development of thyroid malignancy was detected.
Another study reported that the risk of malignancy in thyroid nodule patients with or without HT is similar. Lizis-Kolus et al. found that the concentrations of calcidiol were low and similar between the two groups.
Kim et al. was among the first to emphasize the association between antiTG positivity and TC (OR, 1.61). Boi et al. also suggested that thyroid autoantibodies (TAB) positivity in thyroid nodular cases may be a risk factor for suspicious or malignant cytology. Wu 's study supported this situation as well. Fiore emphasized the weakness of this relationship.
Azizi et al. stated a relationship between TAB and TC development, especially in male patients. In our study, we found malignancy in 2 out of 6 males (33.3%) and 21 out of 38 females (55%) among the antibody-positive patients and there was no statistical significance (P: 0,31).
In the National Health and Nutrition Examination Survey (NHANES), the association of antiTG and antiTPO was found to be more pathologic than antiTG alone. We found malignancy in 60% of patients with single antibody positive (17/28) and in 37% of patients with both antibodies positive (6/16), yet we did not detect any meaning (P: 0,13).
Some studies revealed a relationship between TC and only antiTG by assessing thyroid fine needle aspiration biopsy (FNAB),, whereas Gabalec et al. suggested that antiTG and antiTPO status have no effect on TC risk. Our study confirms the latter one.
In our study, we could not analyze whether Vitamin D adequacy affects the outcome or not, because vitamin D was insufficient or deficient in all groups except 2 cases. This is the weak point of our study.
| Conclusion|| |
In conclusion, according to results of our study lack of vitamin D deficiency and thyroid autoantibody positivity had no effect on the development of thyroid malignancy and metastasis separately or together and the inadequacy at each level was similar in the benign and malignant group. However, in order to reach a clear knowledge on this issue, there is a need for wider prospective studies involving healthy individuals with adequate vitamin D levels.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Schneider AB, Ron E. Carcinoma of follicular epithelium. In: Braverman LE, Utiger RD editors. Werner and Ingbar's the Thyroid. 8th
ed. Philadelphia: Lippincott Williams and Wilkins; 2000. p. 878-86.
Kasper DL. Harrison's Principles of Internal Medicine. New York: McGraw Hill Education, 2015.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin 2017;67:7-30.
Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer 2014;14:342-57.
Danilovic DL, Hoff AO. 25-Hydroxyvitamin D and TSH as risk factors or prognostic markers in thyroid carcinoma. PLoS One 2016;13:1-12.
Holick MF. Vitamin D: Its role in cancer prevention and treatment. Prog Biophys Mol Biol 2006;92:49-59.
Laney N, Meza J, Lyden E, Erickson J, Treude K, Goldner W. The prevalence of vitamin D deficiency is similar between thyroid nodule and thyroid cancer patients. Int J Endocrinol 2010;2010. doi: 10.1155/2010/805716.
Jonklaas J, Danielsen M, Wang H. A pilot study of serum selenium, vitamin D, and thyrotropin concentrations in patients with thyroid cancer. Thyroid 2013;23:1079-86.
Roskies M, Dolev Y, Caglar D, Hier MP, Mlynarek A, Majdan A, et al
. Vitamin D deficiency as a potentially modifiable risk factor for thyroid cancer. J Otolaryngol Head Neck Surg 2012;41:160-3.
Sahin M, Ucan B, Ginis Z, Topaloğlu O, Güngüneş A, Bozkurt NÇ, et al
. Vitamin D3 levels and insulin resistance in papillary thyroid cancer patients. Med Oncol 2013;30:589.
Balkwill F, Mantovani A. Inflammation and cancer: Back to Virchow? Lancet 2001;357:539-45.
Bernatsky S, Ramsey-Goldman R, Clarke A. Malignancy and autoimmunity. Curr Opin Rheumatol 2006;18:129-34.
Kim KW, Park YJ, Kim EH, Park SY, Park DJ, Ahn SH, et al
. Elevated risk of papillary thyroid cancerin Korean patients with Hashimoto's thyroiditis. Head Neck 2011;33:691-5.
Wong SL, Grodski S, Yeung MJ, Serpell JW. Anti-thyroid antibodies as a predictor of thyroid cancer. ANZ J Surg 2013;85:849-53.
Gabalec F, Srbova L, Nova M, Hovorkova E, Hornychova H, Jakubikova I, et al
. Jan cap impact of Hashimoto's thyroiditis, TSH levels, and anti-thyroid antibody positivity on differentiated thyroid carcinoma incidence. Endokrynologia Polska 2016;33:48-53.
Mazokopakis EE, Tzortzinis AA, Dalieraki-Ott EI, Tsartsalis AN, Syros PK, Karefilakis CM, et al
. Coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma. A retrospective study. Hormones (Athens) 2010;9:312-7.
Giagourta I, Evangelopoulou C, Papaioannou G, Kassi G, Zapanti E, Prokopiou M, et al
. Autoimmune thyroiditis in benign and malignant thyroid nodules: 16-year results. Head Neck 2014;36:531-5.
Jankovic B, Le KT, Hershman JM. Clinical review: Hashimoto's thyroiditis and papillary thyroid carcinoma: Is there a correlation? J Clin Endocrinol Metab 2013;98:474-82.
Zhang Y, Dai J, Wu T, Yang N, Yin Z. The study of the coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma. J Cancer Res Clin Oncol 2014;140:1021-6.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon MC, 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.
Stepien T, Krupinski R, Sopinski J, Kuzdak K, Komorowski J, Lawnicka H, et al
. Decreased 1-25 dihydroxyvitamin D3 concentration in peripheral blood serum of patients with thyroid cancer. Arch Med Res 2010;41:190-4.
Kim JR, Kim BH, Kim SM, Oh MY, Kim WJ, Jeon YK, et al
. Low serum 25 hydroxyvitamin D is associated with poor clinicopathologic characteristics in female patients with papillary thyroid cancer. Thyroid 2014;24:1618-24.
Lun Y, Wu X, Xia Q, Han Y, Zhang X, Liu Z, et al
. Hashimoto's thyroiditis as a risk factor of papillary thyroid cancer may improve cancer prognosis. Otolaryngol Head Neck Surg 2013;148:396-402.
Lizis-Kolus K, Hubalewska-Dydejczyk A, Trofimiuk-Muldnerz M, Sowa-Staszczak A, Kowalska A. Assessment of 25(OH) D3, concentration levels in patients with papillary thyroid cancer compared to patients with Hashimoto's thyroiditis. Przegl Lek 2013;70:920-5.
Boi F, Minerba L, Lai ML, Marziani B, Figus B, Spanu F, et al
. Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules. J. Endocrinol Invest 2013;36:313-20.
Wu X, Lun Y, Jiang H, Gang Q, Xin S, Duan Z, et al
. Coexistence of thyroglobulin antibodies and thyroid peroxidase antibodies correlates with elevated thyroid-stimulating hormone level and advanced tumor stage of papillary thyroid cancer. Endocrine 2014;46:554-60.
Fiore E, Rago T, Scutari M, Ugolini C, Proietti A, Di Coscio G, et al
. Papillary thyroid cancer, although strongly associated with lymphocytic infiltration on histology, is only weakly predicted by serum thyroid auto-antibodies in patients with nodular thyroid diseases. J. Endocrinol Invest 2009;32:344-51.
Azizi G, Malchoff CD. Assured autoimmune thyroid disease is a risk factor for thyroid cancer. Endocr Pract 2010;14:1-21.
Spencer CA, Hollowell JG, Kazarosyan M, Braverman LE. National health and nutrition examination survey III thyroidstimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limit may be skewed by occult thyroid dysfunction. J Clin Endocrinol Metab 2007;92:4236-40.
[Table 1], [Table 2], [Table 3], [Table 4]