• Muhammad Naeem Khan
  • Muhammad Qamar Masood Aga Khan University Hospital Karachi
  • Muhammad Arsalan Siddiqui Dow Medical College Karachi
  • Sabahat Naz Aga Khan University Hospital Karachi
  • Najmul Islam Aga Khan University Hospital Karachi


Background: Hypercalcemia is a common clinical problem; primary hyperparathyroidism and malignancy is commonest causes of hypercalcemia. Aetiology of hypercalcemia are changing, causes that were diseases of the past like Vitamin-D toxicity and milk alkali syndrome are observed more often. Vitamin-D deficiency is an important problem and overzealous replacement of Vitamin-D has been observed, suspected to cause toxicity. Method: This was a retrospective review of patients admitted at the Aga Khan University Hospital from January 2008 to December 2013 with hypercalcemia. We reviewed the electronic health records for laboratory and radiological studies, and discharge summaries to establish the cause of hypercalcemia. Patients with solid tumour malignancy were excluded from the analysis. The treatment records and hospital course of patients diagnosed with Vitamin-D toxicity were also reviewed. Results: Primary hyperparathyroidism was the most common cause of hypercalcemia comprising 41 (28.2 %) patients. Vitamin-D toxicity was present in 25 (17.3%) and probable Vitamin-D toxicity 11 (7.6 %) inpatients. Vitamin-D toxicity and probable Vitamin-D toxicity together comprised 36 (24.8%) cases. Other causes of hypercalcemia included multiple myeloma 18 (12.4%) patients, tuberculosis 6 (4.1%) patients, chronic kidney disease6 (4.1%) cases, sarcoidosis 4 (2.7%) and lymphoma 3 (2.0%) patients. In 29(20%) patients a cause of hypercalcemia could not be determined and were labelled as undiagnosed cases. Conclusion: Vitamin-D toxicity was the second commonest cause of hypercalcemia after primary hyperparathyroidism. Knowledge of the prevalent and emerging causes of hypercalcemia is important for prompt diagnosis and treatment.Keywords: Vitamin-D toxicity; Hyperparathyroidism; Hypercalcemia


Ratcliffe WA, Hutchesson AC, Bundred NJ, Ratcliffe JG. Role of assays for parathyroid-hormone-related protein in investigation of hypercalcaemia. Lancet 1992;339(8786):164–7.

Jacobs TP, Bilezikian JP. Clinical review: Rare causes of hypercalcemia. J Clin Endocrinol Metab 2005;90(11):6316–22.

Newman EM, Bouvet M, Borgehi S, Herold DA, Deftos LJ. Causes of Hypercalcemia in a population of military veterans in the United States. Endocr Pract 2006;12(5):535–41.

Mansoor S, Siddiqui I, Adil S, Kakapeto GN, Fatmi Z. Frequency of hypercalcemia in patients of multiple myeloma in Karachi. J Coll Physicians Surg Pak 2005;15(7):409–12.

Masood MQ, Khan AH, Awan S, Dar F, Naz S, Naureen G, et al. Comparison of Vitamin-D replacement strategies with high dose intramuscular or oral cholecalciferol: A prospective interventional study. Endocr Pract 2015;21(10):1125–33.

Khan AH, Majid H, Iqbal R. Shifting of Vitamin-D deficiency to hypervitaminosis and toxicity. J Coll Physicians Surg Pak 2014;24(7):536.

Bansal RK, Tyagi P, Sharma P, Singla V, Arora V, Bansal N, et al. Iatrogenic hypervitaminosis D as an unusual cause of persistent vomiting: a case report. J Med Case Rep 2014;8:74.

Chiricone D, De Santo NG, Cirillo M. Unusual cases of chronic intoxication by Vitamin-D. J Nephrol 2003;16(6):917–21.

Klontz KC, Acheson DW. Dietary supplement-induced Vitamin-D intoxication. N Engl J Med 2007;357(3):308–9.

Koutkia P, Chen TC, Holick MF. Vitamin-D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345(1):66–7.

Minisola S, Pepe J, Piemonte S, Cipriani C. The diagnosis and management of hypercalcaemia. BMJ 2015;350:h2723.

Marcocci C, Cetani F. Primary Hyperparathyroidism. N Engl J Med 2011;365(25):2389–97.

Wermers RA, Khosla S, Atkinson EJ, Achenbach SJ, Oberg AL, Grant CS, et al. Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: an update on the changing epidemiology of the disease. J Bone Miner Res 2006;21(1):171–7.

Kukora JS, Zeiger MA. The American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons position statement on the diagnosis and management of primary hyperparathyroidism. Endocr Pract 2005;11(1):49–54.

Koul PA, Ahmad SH, Ahmad F, Jan RA, Shah SU, Khan UH. Vitamin-D Toxicity in Adults: A Case Series from an Area with Endemic Hypovitaminosis D. Oman Med J 2011;6(3):201–4.

Luxwolda MF, Kuipers RS, Kema IP, Dijck-Brouwer DA, Muskiet FA. Traditionally living populations in East Africa have a mean serum 25-hydroxyVitamin-D concentration of 115 nmol/l. Br J Nutr 2012;108(9):1557–61.

Marcus JF, Shalev SM, Harris CA, Goodin DS, Josephson SA. Severe Hypercalcemia Following Vitamin-D Supplementation in a Patient with Multiple Sclerosis: a note of caution. Arch Neurol 2012;69(1):129–32.

Natalie EC, John PB. Parathyroid Hormone in the Evaluation of Hypercalcemia. JAMA 2014;312(24):2680–1.

Basso SM, Lumachi F, Nascimben F, Luisetto G, Camozzi V. Treatment of acute hypercalcemia. Med Chem 2012;8(4):564–8.

Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, 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(7):1911–30.

Del Valle HB, Yaktine AL, Taylor CL, Ross AC. Dietary reference intakes for calcium and Vitamin-D. National Academies Press; 2011.



Most read articles by the same author(s)