Clinical manifestations of hypocalcemia
- David Goltzman, MD
David Goltzman, MD
- Professor of Medicine
- McGill University
- Senior Physician, Division of Endocrinology and Department of Medicine
- McGill University Health Centre
Hypocalcemia may be associated with a spectrum of clinical manifestations (table 1), ranging from few (if any) symptoms if the hypocalcemia is mild, to life-threatening seizures, refractory heart failure, or laryngospasm if it is severe. In addition to severity, the rate of development of hypocalcemia and chronicity determine the clinical manifestations.
Among the symptoms of hypocalcemia, tetany, papilledema, and seizures may occur in patients who develop hypocalcemia acutely. By comparison, ectodermal and dental changes, cataracts, basal ganglia calcification, and extrapyramidal disorders are features of chronic hypocalcemia. These last findings are most common in patients with hypoparathyroidism.
The clinical manifestations of hypocalcemia are discussed here. The etiology of, diagnostic approach to, and treatment of hypocalcemia are discussed separately. (See "Etiology of hypocalcemia in adults" and "Diagnostic approach to hypocalcemia" and "Treatment of hypocalcemia" and "Hypoparathyroidism".)
The hallmark of acute hypocalcemia is tetany, which is characterized by neuromuscular irritability. The symptoms of tetany may be mild (perioral numbness, paresthesias of the hands and feet, muscle cramps) or severe (carpopedal spasm, laryngospasm, and focal or generalized seizures, which must be distinguished from the generalized tonic muscle contractions that occur in severe tetany) (table 1). Other patients have less specific symptoms, such as fatigue, hyperirritability, anxiety, and depression, and some patients, even with severe hypocalcemia, have no neuromuscular symptoms.
Tetany — Acute hypocalcemia directly increases peripheral neuromuscular irritability . As measured electromyographically, tetany consists of repetitive, high-frequency discharges after a single stimulus. Hyperexcitability of peripheral neurons is probably the most important pathophysiologic effect of hypocalcemia, but hyperexcitability occurs at all levels of the nervous system, including motor endplates, the spinal reflexes, and the central nervous system.
- Macefield G, Burke D. Paraesthesiae and tetany induced by voluntary hyperventilation. Increased excitability of human cutaneous and motor axons. Brain 1991; 114 ( Pt 1B):527.
- Tohme JF, Bilezikian JP. Hypocalcemic emergencies. Endocrinol Metab Clin North Am 1993; 22:363.
- Navarro J, Oster JR, Gkonos PJ, et al. Tetany induced on separate occasions by administration of potassium and magnesium in a patient with hungry-bone syndrome. Miner Electrolyte Metab 1991; 17:340.
- Cohen L. Potassium replacement associated with the development of tetany in a patient with hypomagnesaemia. Magnes Res 1993; 6:43.
- Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ 2008; 336:1298.
- Thakker RV. Hypocalcemia: Pathogenesis, differential diagnosis, and management. In: Primer on the metabolic bone diseases and disorders of mineral metabolism, 6th ed, Favus MJ. (Ed), American Society of Bone and Mineral Research, Washington, DC 2006. p.213.
- Armelisasso C, Vaccario ML, Pontecorvi A, Mazza S. Tonic-clonic seizures in a patient with primary hypoparathyroidism: a case report. Clin EEG Neurosci 2004; 35:97.
- Mrowka M, Knake S, Klinge H, et al. Hypocalcemic generalised seizures as a manifestation of iatrogenic hypoparathyroidism months to years after thyroid surgery. Epileptic Disord 2004; 6:85.
- Zuckermann EC, Glaser GH. Anticonvulsive action of increased calcium concentration in cerebrospinal fluid. Arch Neurol 1973; 29:245.
- Swash M, Rowan AJ. Electroencephalographic criteria of hypocalcemia and hypercalcemia. Arch Neurol 1972; 26:218.
- Denlinger JK, Nahrwold ML. Cardiac failure associated with hypocalcemia. Anesth Analg 1976; 55:34.
- Ghent S, Judson MA, Rosansky SJ. Refractory hypotension associated with hypocalcemia and renal disease. Am J Kidney Dis 1994; 23:430.
- Brunelli SM, Sibbel S, Do TP, et al. Facility Dialysate Calcium Practices and Clinical Outcomes Among Patients Receiving Hemodialysis: A Retrospective Observational Study. Am J Kidney Dis 2015; 66:655.
- Thurlow JS, Yuan CM. Dialysate-induced hypocalcemia presenting as acute intradialytic hypotension: A case report, safety review, and recommendations. Hemodial Int 2016; 20:E8.
- Shinoda T, Aizawa T, Shirota T, et al. Exacerbation of latent heart failure by mild hypocalcemia after parathyroidectomy in a long-term hemodialysis patient. Nephron 1992; 60:482.
- Kazmi AS, Wall BM. Reversible congestive heart failure related to profound hypocalcemia secondary to hypoparathyroidism. Am J Med Sci 2007; 333:226.
- Levine SN, Rheams CN. Hypocalcemic heart failure. Am J Med 1985; 78:1033.
- Wong CK, Lau CP, Cheng CH, et al. Hypocalcemic myocardial dysfunction: short- and long-term improvement with calcium replacement. Am Heart J 1990; 120:381.
- Kudoh C, Tanaka S, Marusaki S, et al. Hypocalcemic cardiomyopathy in a patient with idiopathic hypoparathyroidism. Intern Med 1992; 31:561.
- Brunvand L, Hågå P, Tangsrud SE, Haug E. Congestive heart failure caused by vitamin D deficiency? Acta Paediatr 1995; 84:106.
- Rimailho A, Bouchard P, Schaison G, et al. Improvement of hypocalcemic cardiomyopathy by correction of serum calcium level. Am Heart J 1985; 109:611.
- Benoit SR, Mendelsohn AB, Nourjah P, et al. Risk factors for prolonged QTc among US adults: Third National Health and Nutrition Examination Survey. Eur J Cardiovasc Prev Rehabil 2005; 12:363.
- Meyer T, Ruppert V, Karatolios K, Maisch B. Hereditary long QT syndrome due to autoimmune hypoparathyroidism in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. J Electrocardiol 2007; 40:504.
- Bajandas FJ, Smith JL. Optic nueritis in hypoparathyroidism. Neurology 1976; 26:451.
- Sheldon RS, Becker WJ, Hanley DA, Culver RL. Hypoparathyroidism and pseudotumor cerebri: an infrequent clinical association. Can J Neurol Sci 1987; 14:622.
- Hochman HI, Mejlszenkier JD. Cataracts and pseudotumor cerebri in an infant with vitamin D-deficiency rickets. J Pediatr 1977; 90:252.
- Lin KF, Chen KH, Huang WL. Organic anxiety in a woman with breast cancer receiving denosumab. Gen Hosp Psychiatry 2015; 37:192.e7.
- Tafaj O, Jüppner H. Pseudohypoparathyroidism: one gene, several syndromes. J Endocrinol Invest 2017; 40:347.
- Roszko KL, Bi RD, Mannstadt M. Autosomal Dominant Hypocalcemia (Hypoparathyroidism) Types 1 and 2. Front Physiol 2016; 7:458.
- ACUTE MANIFESTATIONS
- - Trousseau's sign
- - Chvostek's sign
- Psychiatric manifestations
- DISEASE-SPECIFIC MANIFESTATIONS
- Vitamin D deficiency
- Autosomal dominant hypocalcemia
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS