Clinical manifestations of hypercalcemia
- Elizabeth Shane, MD
Elizabeth Shane, MD
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
Hypercalcemia can be produced by a variety of disorders, but primary hyperparathyroidism and malignancy account for most cases. (See "Etiology of hypercalcemia".) It may be associated with a spectrum of clinical manifestations (table 1), ranging from few if any symptoms if the hypercalcemia is mild and/or chronic to obtundation and coma if it is severe and/or acute . The symptoms and signs associated with hypercalcemia are typically independent of the etiology .
Patients with mild hypercalcemia (calcium <12 mg/dL [3 mmol/L]) may be asymptomatic, or they may report nonspecific symptoms, such as constipation, fatigue, and depression. A serum calcium of 12 to 14 mg/dL (3 to 3.5 mmol/L) may be well-tolerated chronically, while an acute rise to these concentrations may cause marked symptoms, including polyuria, polydipsia, dehydration, anorexia, nausea, muscle weakness, and changes in sensorium. In patients with severe hypercalcemia (calcium >14 mg/dL [3.5 mmol/L]), there is often progression of these symptoms [1,2].
This topic will review those symptoms directly associated with hypercalcemia. The clinical manifestations more directly associated with hyperparathyroidism and the diagnostic approach to and treatment of hypercalcemia are discussed separately. (See "Clinical manifestations of primary hyperparathyroidism" and "Diagnostic approach to hypercalcemia" and "Treatment of hypercalcemia".)
A number of mild neuropsychiatric disturbances have been associated with hypercalcemia, mostly in patients with primary hyperparathyroidism. The most common symptoms have been anxiety, depression, and cognitive dysfunction. Improvement in some or all of these symptoms has been described after correction of the hyperparathyroidism, but these reports are of uncontrolled cases and therefore difficult to evaluate. (See "Clinical manifestations of primary hyperparathyroidism", section on 'Neuropsychiatric disturbances' and "Management of primary hyperparathyroidism", section on 'Neuropsychiatric'.)
More severe symptoms, including lethargy, confusion, stupor, and coma may occur in patients with severe hypercalcemia (calcium >14 mg/dL [3.5 mmol/L]) from any cause . These symptoms are more likely to occur in the elderly and in those with rapidly rising calcium concentrations [2,3].
- Shane, E, Dinaz, I. Hypercalcemia: Pathogenesis, clinical manifestations, differential diagnosis, and managment. In: Favus, MJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. Sixth ed. Philadelphia: Lippincott, Williams, and Wilkins. 2006; 26:176.
- Inzucchi SE. Understanding hypercalcemia. Its metabolic basis, signs, and symptoms. Postgrad Med 2004; 115:69.
- Ohrvall U, Akerström G, Ljunghall S, et al. Surgery for sporadic primary hyperparathyroidism in the elderly. World J Surg 1994; 18:612.
- Gardner EC Jr, Hersh T. Primary hyperparathyroidism and the gastrointestinal tract. South Med J 1981; 74:197.
- Carnaille B, Oudar C, Pattou F, et al. Pancreatitis and primary hyperparathyroidism: forty cases. Aust N Z J Surg 1998; 68:117.
- Gaur S. Sarcoidosis manifested as hypercalcemic pancreatitis. South Med J 2001; 94:939.
- Wynn D, Everett GD, Boothby RA. Small cell carcinoma of the ovary with hypercalcemia causes severe pancreatitis and altered mental status. Gynecol Oncol 2004; 95:716.
- Bourgain A, Acker O, Lambaudie E, et al. [Small cell carcinoma of the ovary of the hypercalcemic type revealed by a severe acute pancreatitis: about one case]. Gynecol Obstet Fertil 2005; 33:35.
- Mithöfer K, Fernández-del Castillo C, Frick TW, et al. Acute hypercalcemia causes acute pancreatitis and ectopic trypsinogen activation in the rat. Gastroenterology 1995; 109:239.
- Ward JB, Petersen OH, Jenkins SA, Sutton R. Is an elevated concentration of acinar cytosolic free ionised calcium the trigger for acute pancreatitis? Lancet 1995; 346:1016.
- Norton JA, Cornelius MJ, Doppman JL, et al. Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger-Ellison syndrome, and multiple endocrine neoplasia type I: a prospective study. Surgery 1987; 102:958.
- Caruana RJ, Buckalew VM Jr. The syndrome of distal (type 1) renal tubular acidosis. Clinical and laboratory findings in 58 cases. Medicine (Baltimore) 1988; 67:84.
- 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; 71:1624.
- Lins LE. Reversible renal failure caused by hypercalcemia. A retrospective study. Acta Med Scand 1978; 203:309.
- Peacock M. Primary hyperparathyroidism and the kidney: biochemical and clinical spectrum. J Bone Miner Res 2002; 17 Suppl 2:N87.
- Ahmed R, Hashiba K. Reliability of QT intervals as indicators of clinical hypercalcemia. Clin Cardiol 1988; 11:395.
- Rosenqvist M, Nordenström J, Andersson M, Edhag OK. Cardiac conduction in patients with hypercalcaemia due to primary hyperparathyroidism. Clin Endocrinol (Oxf) 1992; 37:29.
- Kiewiet RM, Ponssen HH, Janssens EN, Fels PW. Ventricular fibrillation in hypercalcaemic crisis due to primary hyperparathyroidism. Neth J Med 2004; 62:94.
- Diercks DB, Shumaik GM, Harrigan RA, et al. Electrocardiographic manifestations: electrolyte abnormalities. J Emerg Med 2004; 27:153.
- Nishi SP, Barbagelata NA, Atar S, et al. Hypercalcemia-induced ST-segment elevation mimicking acute myocardial infarction. J Electrocardiol 2006; 39:298.
- Turhan S, Kilickap M, Kilinc S. ST segment elevation mimicking acute myocardial infarction in hypercalcaemia. Heart 2005; 91:999.
- Ashizawa N, Arakawa S, Koide Y, et al. Hypercalcemia due to vitamin D intoxication with clinical features mimicking acute myocardial infarction. Intern Med 2003; 42:340.
- Roberts WC, Waller BF. Effect of chronic hypercalcemia on the heart. An analysis of 18 necropsy patients. Am J Med 1981; 71:371.
- Albright F, Reifenstein EC Jr. The Parathyroid Glands and Metabolic Bone Disease: Selected Cases, The Williams and Wilkins Company, Baltimore 1948.
- Chou FF, Sheen-Chen SM, Leong CP. Neuromuscular recovery after parathyroidectomy in primary hyperparathyroidism. Surgery 1995; 117:18.
- Wilson KS, Alexander S, Chisholm IA. Band keratopathy in hypercalcemia of myeloma. Can Med Assoc J 1982; 126:1314.