Hyper vitaminosis D: are we overprescribing vitamin D?

[Downloaded free from http://www.jfmpc.com on Thursday, January 01, 2015, IP: 163.47.15.163] || Click here to download free Android application for this journal Case Report Hyper Vitaminosis D: Are we Overprescribing Vitamin D? Hemachandar R, Lokesh Shanmugam1, Balakrishna Malepati1, Suresh Venugopal1 Departments of Nephrology, and 1General Medicine, Mahatma Gandhi Medical College and Research Institute, Puducherry, India A bstract Vitamin D, the sunshine vitamin is now considered to be a hormone due to its important role in many physiological functions. Vitamin D deficiency has been associated with many disorders ranging from bone diseases, cardiovascular diseases to cancer. Hence, there is a recent surge in the empirical prescription of vitamin D for various disorders without documentation of vitamin D deficiency and monitoring the treatment. We report a case of iatrogenic hypercalcemia and acute kidney injury due to vitamin D toxicity after empirical and overzealous use of vitamin D and calcium supplements. We present this case to remind clinicians the importance of monitoring the patients treated with mega doses of vitamin D. Keywords: Acute kidney injury, cholecalciferol, hyper vitaminosis D, iatrogenic hypercalcemia 18 mm/1 h, urine analysis showed no proteinuria and no deposits, urea 120 mg/dL, creatinine 2.2 mg/dL, Na 130 mEq/L, potassium 3.6 mEq/L, calcium 13.7 mg/dL, phosphorus 3.0 mg/dL, serum bilirubin 0.9 mg/dL, albumin 3.2 g/dL, total protein 5.6 g/dL, alanine transaminase 38 IU/L, aspartate transaminase 42 IU/L, and alkaline phosphatase 155 IU/L. X‑ray of spine showed lumbar spondylolisthesis of L5 over S1 and diffuse rarefaction of bone [Figure 1]. Magnetic resonance imaging of lumbosacral spine showed lumbar spondylolisthesis of L5 over S1 [Figure 2]. Bone mineral density by Dual‑energy X‑ray absorptiometry scan was suggestive of osteoporosis with a T score of −2.9 and Z score of −2.4. Introduction Activated vitamin D (1,25 OH vitamin D) plays a crucial role in a plethora of physiological functions. Vitamin D deficiency is associated with various illnesses other than disorders of calcium metabolism, including infectious diseases, autoimmune diseases, cardiovascular disease, type 2 diabetes mellitus, and some cancers.[1] Hence, vitamin D is now a frequently prescribed drug for various disorders. Unfortunately, there is lack of awareness of the various preparations and dosages of this hormone. This occasionally leads to avoidable errors in prescription, leading to unwanted side effects. Case Report The patient was managed by continuous saline infusion, diuretics, and bisphosphonates. Parathyroid hormone (PTH) was 13.54 pg/mL and vitamin D 25(OH) was >150 ng/mL. Retrospectively, while reviewing her previous medical prescriptions, it was found that she had received multiple prescriptions of oral calcium carbonate, oral cholecalciferol, and oral calcitriol over the last 2 years. Two months earlier, she had also received intramuscular injections of cholecalciferol 600,000 IU daily for 20 consecutive days. Serum and urine protein electrophoresis was negative for M protein. Malignancy screen was negative. A 46‑year‑old female patient was referred to the Department of Nephrology for evaluation of renal failure. She gave a history of low backache for the past 2 years. Since then, she has been on several medications. She denied history of reduced urine output or pedal edema. Her blood pressure was 110/80 mm of Hg. Neurological examination was significant for tenderness and bony step at the level of L5. Her motor and sensory examination was normal. The laboratory investigations revealed the following results: Hemoglobin 9.4 g/dL, erythrocyte sedimentation rate Patient was advised surgery for spondylolisthesis for which the relatives refused to. She was discharged after 2 weeks with serum calcium and creatinine of 12.1 mg/dL and Access this article online Quick Response Code: Website: www.jfmpc.com Address for correspondence: Dr. Hemachandar R, Department of Nephrology, Mahatma Gandhi Medical College and Research Institute, Pondy ‑Cuddalore Main Road, Pillaiyarkuppam, Puducherry ‑ 607 402, India. E‑mail: [email protected] DOI: 10.4103/2249-4863.148153 Journal of Family Medicine and Primary Care 464 October 2014 : Volume 3 : Issue 4 [Downloaded free from http://www.jfmpc.com on Thursday, January 01, 2015, IP: 163.47.15.163] || Click here to download free Android application for this journal Hemachandar, et al.: Vitamin D toxicity Figure 1: X-ray lumbosacral spine spine lateral view showing spondylolisthesis of L5 over S1 Figure 2: Magnetic resonance imaging spine showing spondylolisthesis of L5 over S1 1.6 mg/dL, respectively. During her last follow‑up, her calcium was 10.9 mg/dL and creatinine was 1.1 mg/dL. She was started on oral bisphosphonates for osteoporosis. toxic in huge doses and reports of vitamin D toxicity exist in literature.[5] Vitamin D intoxication usually occurs at levels of 25(OH) vitamin D > 150 ng/mL.[6] The clinical manifestations are kidney disorders (65.0%), renal insufficiency (51.0%), gastrointestinal tract disorders (23.0%), and arterial hypertension (52.0%).[7] Discussion Vitamin D has achieved increasing prominence over the past few decades in the research publications. 1,25(OH) 2D3 is now considered to be a steroid hormone and functions the same way as other steroid hormones by interacting with its vitamin D receptor (VDR). Over the past several decades, various research has shown that the VDR is widely distributed among various body tissues than previously thought (intestine, bone, kidney, and parathyroid).[2] The pluripotent steroid hormone 1,25(OH) 2D3 initiates the physiologic responses of at least 36 cell types that possess the VDR. In addition to the production of circulating 1,25(OH) 2D3 in the kidneys, researchers have found a paracrine production of this steroid hormone in at least 10 extra renal organs. The management of these patients includes withdrawal of the offending agent/s, intravenous volume expansion, furosemide, bisphosphonates and hydrocortisone in selected cases. Complete recovery of renal function can occur if the diagnosis is made early in the course of the disease. In our patient, hypercalcemia was parathyroid independent, as the serum levels of PTH was low normal. The malignancy as the cause of hypercalcemia was ruled out by absence of clinical and laboratory evidence of malignancy. Conclusion The toxic potential of mega doses of vitamin D therapy is still not generally appreciated among health care providers. This case report highlights that large doses of vitamin D prescribed without adequate supervision can be potentially toxic despite its wide margin of safety. This case questions the rationale behind empirical treatment with vitamin D and calcium supplements. Vitamins are generally considered to be beneficial and not harmful. Nevertheless to say anything that is overdone becomes dangerous. Vitamin D has been found to have important role the adaptive immune system, the innate immune system, insulin secretion by the pancreatic β cell, myocardial functioning, blood pressure regulation, and brain and fetal development.[2] Vitamin D depletion has been associated with increased risk of osteoporosis, hip fracture in the elderly, hypertension, cardiovascular disease, and some types of malignancies.[1] Vitamin D deficiency prevails in epidemic proportions even in a tropical country like India, with a prevalence of 70%–100% in the general population.[3] Therefore, it is not surprising that vitamin D supplements are being prescribed for various diseases. Many patients are given vitamin D supplements empirically in doses much beyond the recommended doses, without the laboratory evidence of vitamin D deficiency and without monitoring. References In patients taking vitamin D preparations monitoring should be done by periodic estimation of 24‑h urinary calcium excretion, which should not exceed 250 mg.[4] Vitamin D is Journal of Family Medicine and Primary Care 465 1. Gröber U, Spitz J, Reichrath J, Kisters K, Holick MF. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermatoendocrinol 2013;5:331‑47. 2. Norman AW. From vitamin D to hormone D: Fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 2008;88:491S‑9. 3. G R, Gupta A. Vitamin D deficiency in India: Prevalence, causalities and interventions. Nutrients 2014;6:729‑75. October 2014 : Volume 3 : Issue 4 [Downloaded free from http://www.jfmpc.com on Thursday, January 01, 2015, IP: 163.47.15.163] || Click here to download free Android application for this journal Hemachandar, et al.: Vitamin D toxicity 4. 5. Brighurst FR, Demay MB, Krane SM, Kronenberg HM. Bone and mineral metabolism in health and diseases. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison’s Principles of Internal Medicine. 17th ed., Vol. 2. New York: McGraw Hill; 2008. p. 2365‑77. View publication stats Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266‑81. 7. Rudneva LF, Androsova LA. Long‑term outcomes after acute vitamin D3 intoxication. Vopr Pitan 2004;73:11‑3. How to cite this article: Hemachandar R, Shanmugam L, Malepati B, Venugopal S. Hyper vitaminosis D: are we overprescribing vitamin D?. J Fam Med Primary Care 2014;3:464-6. Pandita KK, Razdan S, Kudyar RP, Beigh A, Kuchay S, Banday T. “Excess gooD can be Dangerous”. A case series of iatrogenic symptomatic hypercalcemia due to hypervitaminosis D. Clin Cases Miner Bone Metab 2012;9:118‑20. Journal of Family Medicine and Primary Care 6. Source of Support: Nil. Conflict of Interest: None declared. 466 October 2014 : Volume 3 : Issue 4