Characteristics and outcome of severe hypercalcemia on admission to the emergency department: a retrospective cohort study
AIMS OF THE STUDY: To investigate the prevalence of hypercalcemia (>2.60 mmol/l) and severe hypercalcemia (≥2.80 mmol/l) on admission. Symptoms, causes, course of serum calcium, treatment and outcome of severe hypercalcemia were evaluated and compared to historical data from previous studies.
METHODS: In this retrospective cohort study, all patients presenting to the interdisciplinary emergency department of the Buergerspital Solothurn between 01 January 2017 and 31 December 2020 with measurements of serum calcium were included. Chart reviews were performed for patients with calcium ≥2.80 mmol/l to assess clinical presentation, course of disease and treatment for severe hypercalcemia.
RESULTS: Of 31,963 tested patients, 869 patients (2.7%) had hypercalcemia on the admission, of which 161 had severe hypercalcemia. Non-albumin corrected calcium was 3.07 (0.32) while albumin corrected calcium was 3.34 (0.44). Calcium was higher in patients with malignancy-related hypercalcemia (3.18 [0.34] versus 3.00 [0.3], p <0.001). Neuropsychiatric (35%) and gastrointestinal (24%) were the leading symptoms. Malignancy was the most common identifiable cause of hypercalcemia (40%), with lung cancer (20%), multiple myeloma (14%) and renal cell carcinoma (11%) being the main cancer types. 36% of patients with severe hypercalcemia took calcium supplements. Bisphosphonate treatment was an independent predictor of a fall in calcium until day 5 (regression coefficient: –0.404, standard error 0.11, p <0.001). Hypercalcemia was not mentioned in the final discharge report in 38% of cases.
CONCLUSION: Severe hypercalcemia is common and malignancy-related in almost half of the cases. Neuropsychiatric and gastrointestinal symptoms were most prevalent. Awareness of hypercalcemia, particularly in cancer patients and those with known triggering factors, should be raised in order to identify and treat this harmful disorder early.
- Arampatzis S , Funk GC , Leichtle AB , Fiedler GM , Schwarz C , Zimmermann H , et al. Impact of diuretic therapy-associated electrolyte disorders present on admission to the emergency department: a cross-sectional analysis. BMC Med. 2013 Mar;11(1):83. https://doi.org/10.1186/1741-7015-11-83
- Akirov A , Gorshtein A , Shraga-Slutzky I , Shimon I . Calcium levels on admission and before discharge are associated with mortality risk in hospitalized patients. Endocrine. 2017 Aug;57(2):344–51. https://doi.org/10.1007/s12020-017-1353-y
- Cheungpasitporn W , Thongprayoon C , Mao MA , Kittanamongkolchai W , Sakhuja A , Erickson SB . Impact of admission serum calcium levels on mortality in hospitalized patients. Endocr Res. 2018 May;43(2):116–23. https://doi.org/10.1080/07435800.2018.1433200
- Tonon CR , Silva TA , Pereira FW , Queiroz DA , Junior EL , Martins D , et al. A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia. Med Sci Monit. 2022 Feb;28:e935821. https://doi.org/10.12659/MSM.935821
- Basso SM , Lumachi F , Nascimben F , Luisetto G , Camozzi V . Treatment of acute hypercalcemia. Med Chem. 2012 Jul;8(4):564–8. https://doi.org/10.2174/157340612801216382
- Endo M . Calcium ion as a second messenger with special reference to excitation-contraction coupling. J Pharmacol Sci. 2006;100(5):519–24. https://doi.org/10.1254/jphs.CPJ06004X
- Kuo IY , Ehrlich BE . Signaling in muscle contraction. Cold Spring Harb Perspect Biol. 2015 Feb;7(2):a006023. https://doi.org/10.1101/cshperspect.a006023
- Landstrom AP , Dobrev D , Wehrens XH . Calcium Signaling and Cardiac Arrhythmias. Circ Res. 2017 Jun;120(12):1969–93. https://doi.org/10.1161/CIRCRESAHA.117.310083
- Carnaille B , Oudar C , Pattou F , Combemale F , Rocha J , Proye C . Pancreatitis and primary hyperparathyroidism: forty cases. Aust N Z J Surg. 1998 Feb;68(2):117–9. https://doi.org/10.1111/j.1445-2197.1998.tb04719.x
- Mousseaux C , Dupont A , Rafat C , Ekpe K , Ghrenassia E , Kerhuel L , et al. Epidemiology, clinical features, and management of severe hypercalcemia in critically ill patients. Ann Intensive Care. 2019 Nov;9(1):133. https://doi.org/10.1186/s13613-019-0606-8
- Lindner G , Felber R , Schwarz C , Marti G , Leichtle AB , Fiedler GM , et al. Hypercalcemia in the emergency department: prevalence, etiology, and outcome. Am J Emerg Med. 2013 Apr;31(4):657–60. https://doi.org/10.1016/j.ajem.2012.11.010
- Nagy L , Mangini P , Schroen C , Aziz R , Tobia A . Prolonged Hypercalcemia-Induced Psychosis. Case Rep Psychiatry. 2020 Feb;2020:6954036. https://doi.org/10.1155/2020/6954036
- Ahmed R , Hashiba K . Reliability of QT intervals as indicators of clinical hypercalcemia. Clin Cardiol. 1988 Jun;11(6):395–400. https://doi.org/10.1002/clc.4960110607
- Abugroun A , Tyle A , Faizan F , Accavitti M , Ahmed C , Wang T . Hypercalcemia-Induced ST-Segment Elevation Mimicking Acute Myocardial Injury: A Case Report and Review of the Literature. Case Rep Emerg Med. 2020 Mar;2020:4159526. https://doi.org/10.1155/2020/4159526
- Chou FF , Sheen-Chen SM , Leong CP . Neuromuscular recovery after parathyroidectomy in primary hyperparathyroidism. Surgery. 1995 Jan;117(1):18–25. https://doi.org/10.1016/S0039-6060(05)80224-7
- Ritter A , Vargas-Poussou R , Mohebbi N , Seeger H . Recurrent Nephrolithiasis in a Patient With Hypercalcemia and Normal to Mildly Elevated Parathyroid Hormone. Am J Kidney Dis. 2021 Jun;77(6):A13–5. https://doi.org/10.1053/j.ajkd.2020.09.022
- Levi M , Ellis MA , Berl T . Control of renal hemodynamics and glomerular filtration rate in chronic hypercalcemia. Role of prostaglandins, renin-angiotensin system, and calcium. J Clin Invest. 1983 Jun;71(6):1624–32. https://doi.org/10.1172/JCI110918
- Lins LE . Reversible renal failure caused by hypercalcemia. A retrospective study. Acta Med Scand. 1978;203(4):309–14.
- Jalbert M , Mignot A , Gauchez AS , Dobrokhotov AC , Fourcade J . [Severe hypercalcemia of unusual cause, looking for the culprit: case report and review of the literature]. Nephrol Ther. 2018 Jun;14(4):231–6. https://doi.org/10.1016/j.nephro.2018.03.003
- Varghese RT , Khasawneh K , Desikan RK , Subramaniam A , Weaver T , Nair GK . Vitamin A and Hydrochlorothiazide Causing Severe Hypercalcemia in a Patient With Primary Hyperparathyroidism. J Investig Med High Impact Case Rep. 2019;7:2324709618823805. https://doi.org/10.1177/2324709618823805
- Dhivyasree S , Dhivyalakshmi J , Sankaranarayanan S , Scott JX . Severe hypercalcemia: A rare and unusual presentation of acute lymphoblastic leukemia. J Cancer Res Ther. 2018 Dec;14(7 Supplement):S1244–6. https://doi.org/10.4103/0973-1482.187240
- Volpicelli G , Mussa A , Frascisco M . A case of severe hypercalcemia with acute renal failure in sarcoidosis: a diagnostic challenge for the emergency department. Eur J Emerg Med. 2005 Dec;12(6):320–1. https://doi.org/10.1097/00063110-200512000-00015
- Acharya R , Winters DM , Rowe C , Buckley N , Kafle S , Chhetri B . An unusual case of severe hypercalcemia: as dehydrated as a bone. J Community Hosp Intern Med Perspect. 2021 Jan;11(1):135–8. https://doi.org/10.1080/20009666.2020.1851859
- Payne RB , Little AJ , Williams RB , Milner JR . Interpretation of serum calcium in patients with abnormal serum proteins. BMJ. 1973 Dec;4(5893):643–6. https://doi.org/10.1136/bmj.4.5893.643
- Gastanaga VM , Schwartzberg LS , Jain RK , Pirolli M , Quach D , Quigley JM , et al. Prevalence of hypercalcemia among cancer patients in the United States. Cancer Med. 2016 Aug;5(8):2091–100. https://doi.org/10.1002/cam4.749
- Catalano A , Chilà D , Bellone F , Nicocia G , Martino G , Loddo I , et al. Incidence of hypocalcemia and hypercalcemia in hospitalized patients: is it changing? J Clin Transl Endocrinol. 2018 May;13:9–13. https://doi.org/10.1016/j.jcte.2018.05.004
- Banu S , Batool S , Sattar S , Masood MQ . Malignant and Non-Malignant Causes of Hypercalcemia: A Retrospective Study at a Tertiary Care Hospital in Pakistan. Cureus. 2021 Jun;13(6):e15845. https://doi.org/10.7759/cureus.15845
- Griebeler ML , Kearns AE , Ryu E , Thapa P , Hathcock MA , Melton LJ 3rd , et al. Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades. J Clin Endocrinol Metab. 2016 Mar;101(3):1166–73. https://doi.org/10.1210/jc.2015-3964
- Desai HV , Gandhi K , Sharma M , Jennine M , Singh P , Brogan M . Thiazide-induced severe hypercalcemia: a case report and review of literature. Am J Ther. 2010;17(6):e234–6. https://doi.org/10.1097/MJT.0b013e3181c6c21b