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Biochemical characteristics and calcium and PTH levels of patients with high normal and elevated serum 25(OH)D levels in Turkey: DeVIT-TOX survey

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Abstract

Summary

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment.

Purpose

We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels.

Methods

An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149–100 ng/mL; and group 3, 99–88 ng/mL.

Results

A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88–455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1–13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p < 0.05). The most common cause (73.5%) associated with high serum 25(OH)D levels was the inappropriate prescription of a high dose of oral vitamin D (600.000–1.500.000 IU) for treating vitamin D deficiency/insufficiency in a short time (1–3 months). The cut-off value of 25 (OH) D level in patients with hypercalcemia was found to be 89 ng/mL [median 116.5 (89–216)].

Conclusions

High dose of vitamin D intake is associated with a high serum 25 OH D level, without symptoms of hypercalcemia. Inappropriate prescription of vitamin D is the primary cause for elevated 25(OH) D levels and related hypercalcemia. Hypercalcemia may not be observed in every patient at very high 25(OH) D levels. Adherence to the recommendation of guidelines is essential to ensure safe and effective treatment of vitamin D deficiency.

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Data availability

The datasets generated for this study are available on request to the corresponding author.

References

  1. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al (2011) Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930. https://doi.org/10.1210/jc.2011-0385

    Article  CAS  PubMed  Google Scholar 

  2. Matsui MS (2020) Vitamin D update. Curr Derm Rep 9:323–330. https://doi.org/10.1007/s13671-020-00315-0

    Article  Google Scholar 

  3. Berridge MJ (2017) Vitamin D deficiency and diabetes. Biochem J 474:1321–1332. https://doi.org/10.1042/BCJ20170042

    Article  CAS  PubMed  Google Scholar 

  4. Sassi F, Tamone C, D’Amelio P (2018) Vitamin D: nutrient, hormone, and immunomodulator. Nutrients 10(11):1656. https://doi.org/10.3390/nu10111656

    Article  CAS  PubMed Central  Google Scholar 

  5. Alfredsson L, Armstrong BK, Butterfield DA, Chowdhury R, de Gruijl FR, Feelisch M, … Young AR (2020) Insufficient sun exposure has become a real public health problem. Int J Environ Res Public Health 17(14):5014.https://doi.org/10.3390/ijerph17145014

  6. Mirhosseini N, Rainsbury J, Kimball SM (2018) Vitamin D supplementation, serum 25(OH)D concentrations and cardiovascular disease risk factors: a systematic review and meta-analysis. Front Cardiovasc Med 12(5):87. https://doi.org/10.3389/fcvm.2018.00087

    Article  CAS  Google Scholar 

  7. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B et al (2019) Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev 40:1109–1151. https://doi.org/10.1210/er.2018-00126

    Article  PubMed  Google Scholar 

  8. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S et al (2019) Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 380:33–44

    Article  CAS  PubMed  Google Scholar 

  9. Lips P, Bilezikian JP, Bouillon R (2019) Vitamin D: giveth to those who needeth. JBMR Plus 4(1):e10232. https://doi.org/10.1002/jbm4.10232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Holick MF (2017) The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 18(2):153–165. https://doi.org/10.1007/s11154-017-9424-1

    Article  CAS  PubMed  Google Scholar 

  11. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281. https://doi.org/10.1056/NEJMra070553

    Article  CAS  PubMed  Google Scholar 

  12. Pludowski P, Holick MF, Grant WB, Konstantynowicz J, Mascarenhas MR, Haq A et al (2018) Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol 175:125–135. https://doi.org/10.1016/j.jsbmb.2017.01.021

    Article  CAS  PubMed  Google Scholar 

  13. Jorde R, Sollid ST, Svartberg J, Schirmer H, Joakimsen RM, Njolstad I et al (2016) Vitamin D 20,000 IU per week for five years does not prevent progression from prediabetes to diabetes. J Clin Endocrinol Metab 101:1647–1655. https://doi.org/10.1210/jc.2015-4013

    Article  CAS  PubMed  Google Scholar 

  14. Scragg R, Khaw KT, Toop L, Sluyter J, Lawes CMM, Waayer D et al (2018) Monthly high-dose vitamin D supplementation and cancer risk: a post hoc analysis of the vitamin D assessment randomized clinical trial. JAMA Oncol 4(11):e182178. https://doi.org/10.1001/jamaoncol.2018.2178

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, Staehelin HB, Meyer OW, Theiler R et al (2016) Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med 176(2):175–183. https://doi.org/10.1001/jamainternmed.2015.7148

    Article  PubMed  Google Scholar 

  16. Khaw KT, Stewart AW, Waayer D, Lawes CMM, Toop L, Camargo CA Jr et al (2017) Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post-hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial. Lancet Diabetes Endocrinol 5(6):438–447. https://doi.org/10.1016/S2213-8587(17)30103-1

    Article  CAS  PubMed  Google Scholar 

  17. Pludowski P, Grant WB, Konstantynowicz J, Holick MF (2019) Editorial: classic and pleiotropic actions of vitamin D. Front Endocrinol (Lausanne) 10:341. https://doi.org/10.3389/fendo.2019.00341

    Article  Google Scholar 

  18. Marcinowska-Suchowierska E, Kupisz-Urbańska M, Łukaszkiewicz J, Płudowski P, Jones G (2018) Vitamin D toxicity-a clinical perspective. Front Endocrinol (Lausanne) 9:550. https://doi.org/10.3389/fendo.2018.00550

    Article  Google Scholar 

  19. Ozkan B, Hatun S, Bereket A (2012) Vitamin D intoxication. Turk J Pediatr 54:93–98

    PubMed  Google Scholar 

  20. Taylor PN, Davies JS (2018) A review of the growing risk of vitamin D toxicity from inappropriate practice. Br J Clin Pharmacol 84:1121–1127. https://doi.org/10.1111/bcp.13573

    Article  PubMed  PubMed Central  Google Scholar 

  21. Varimli D (2021) Ülkemizde D Vitamini Reçetelemesinin ve Tüketiminin Değerlendirilmesi. Thesis, Haceetepe University, Ankara, Turkey

  22. Płudowski P, Karczmarewicz E, Bayer M, Carter G, Chlebna-Sokół D, Czech-Kowalska J et al (2013) Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Endokrynol Pol 64(4):319–327. https://doi.org/10.5603/ep.2013.0012

    Article  PubMed  Google Scholar 

  23. Kucukerdem HS, Arslan M, Koc EM, Can H (2017) Retrospective evaluation of family medicine outpatient clinic profile at a tertiary hospital in İzmir. J Acad Res Med 7(3):112–116. https://doi.org/10.5152/jarem.2017.1165

    Article  Google Scholar 

  24. Al-Yatama FI, AlOtaibi F, Al-Bader MD, Al-Shoumer KA (2019) The effect of clothing on vitamin d status, bone turnover markers, and bone mineral density in young Kuwaiti females. Int J Endocrinol 2019:6794837. https://doi.org/10.1155/2019/6794837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Buyukuslu N, Esin K, Hizli H, Sunal N, Yigit P, Garipagaoglu M (2014) Clothing preference affects vitamin D status of young women. Nutr Res 34(8):688–693. https://doi.org/10.1016/j.nutres.2014.07.012

    Article  CAS  PubMed  Google Scholar 

  26. Bassil D, Rahme M, Hoteit M, Fuleihan Gel-H (2013) Hypovitaminosis D in the Middle East and North Africa: prevalence, risk factors and impact on outcomes. Dermatoendocrinol. 5(2):274–298. https://doi.org/10.4161/derm.25111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lips P, Cashman KD, Lamberg-Allardt C, Bischoff-Ferrari HA, Obermayer-Pietsch B, Bianchi ML, … Bouillon R (2019) Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society. Eur J Endocrinol 180(4):P23–P54.https://doi.org/10.1530/eje-18-0736

  28. Galior K, Grebe S, Singh R (2018) Development of vitamin D toxicity from overcorrection of vitamin D deficiency: a review of case reports. Nutrients 10(8):953. https://doi.org/10.3390/nu10080953

    Article  CAS  PubMed Central  Google Scholar 

  29. Amrein K, Sourij H, Wagner G, Holl A, Pieber TR, Smolle KH et al (2011) Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care 15(2):R104. https://doi.org/10.1186/cc10120

    Article  PubMed  PubMed Central  Google Scholar 

  30. Balk EM, Adam GP, Langberg VN, Earley A, Clark P, Ebeling PR et al (2017) Global dietary calcium intake among adults: a systematic review. Osteoporos Int 28:3315–3324. https://doi.org/10.1007/s00198-017-4230-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ersoy B, Kizilay DÖ, Yilmaz SK, Taneli F, Gümüşer G (2018) Bone mineral density, vitamin D status, and calcium intake in healthy female university students from different socioeconomic groups in Turkey. Arch Osteoporos 13:135. https://doi.org/10.1007/s11657-018-0482-0

    Article  PubMed  Google Scholar 

  32. Kaur P, Mishra SK, Mithal A (2015) Vitamin D toxicity resulting from overzealous correction of vitamin D deficiency. Clin Endocrinol (Oxf) 83:327–331. https://doi.org/10.1111/cen.12836

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Preparation for publication of this article is supported by the Society of Endocrinology and Metabolism of Turkey.

Author information

Authors and Affiliations

  1. Department of Endocrinology, School of Medicine, Dicle University, Diyarbakır, Turkey

    Zafer Pekkolay & Alpaslan Kemal Tuzcu

  2. Department of Endocrinology, School of Medicine, Marmara University, İstanbul, Turkey

    Dilek Gogas Yavuz

  3. Department of Endocrinology, Çanakkale Onsekiz Mart University School of Medicine, Çanakkale, Turkey

    Emre Sedar Saygılı & Ersen Karakılıç

  4. Deparment of Endocrinology, Ufuk University School of Medicine, Ankara, Turkey

    Ceyla Konca Değertekin

  5. Department of Endocrinology, School of Medicine, Zonguldak Bülent Ecevit University, Kocaeli, Turkey

    Ömercan Topaloğlu

  6. Department of Endocrinology, Ankara Training and Research Hospital, Ankara, Turkey

    Çağatay Emir Önder, Işılay Taskaldıran, Sevde Nur Fırat & Tülay Omma

  7. Gazi Yaşargil Training and Research Hospital, Endocrinology Clinic, Diyarbakır, Turkey

    Hikmet Soylu

  8. Department of Endocrinology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey

    Ayşe Esen Pazır

  9. Department of Endocrinology, Fırat University School of Medicine, Elazığ, Turkey

    Kader Uğur & Faruk Kılınç

  10. Department of Endocrinology, Haydarpaşa Numune Training and Research Hospital, İstanbul, Turkey

    Seher Tanrıkulu

  11. Department of Endocrinology, School of Medicine, Akdeniz University, Antalya, Turkey

    Burcu Meryem Atak

  12. Department of Endocrinology, Koç University, School of Medicine, İstanbul, Turkey

    Adnan Batman

  13. Department of Endocrinology, Sultan Abdulhamid Han Training and Research Hospital, University of Health Sciences, İstanbul, Turkey

    Eylem Cağıltay & Adnan Yay

  14. Department of Endocrinology, School of Medicine, Celal Bayar University, Manisa, Turkey

    Nilüfer Özdemir & Zeliha Hekimsoy

  15. Department of Endocrinology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey

    Seher Çetinkaya Altuntaş

  16. Deparment of Endocrinology, Ankara Numune Training and Research Hospital, Ankara, Turkey

    Narin Nasıroğlu İmga

  17. Department of Endocrinology, School of Medicine, Balıkesir University, Balıkesir, Turkey

    Mustafa Eroğlu

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  1. Zafer Pekkolay
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  25. Alpaslan Kemal Tuzcu
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Contributions

DGY conceived and designed the study. DGY, ZP, and ESS analyzed and interpreted the data. DGY, ZP, and ESS drafted and revised the manuscript. All authors have contributed to the work and approved the final version.

Corresponding author

Correspondence to Zafer Pekkolay.

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Written informed consent was obtained from all patients based on the Declaration of Helsinki. The study was approved by the Ethics Committee of Marmara University School of Medicine.

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Pekkolay, Z., Yavuz, D.G., Saygılı, E.S. et al. Biochemical characteristics and calcium and PTH levels of patients with high normal and elevated serum 25(OH)D levels in Turkey: DeVIT-TOX survey. Arch Osteoporos 16, 138 (2021). https://doi.org/10.1007/s11657-021-01002-8

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