Evaluation of hypocalcemia

Diseases

Summary

Hypocalcemia is a state of electrolyte imbalance in which the circulating serum calcium level is low. During hypocalcemia, the total calcium level and the ionized calcium level fall below the laboratory reference range.

Hypocalcemia may occur subsequent to failure of any of the mechanisms by which serum calcium concentration is maintained. But it is usually the result of failure of parathyroid hormone secretion or an inability to release calcium from bone.

The clinical features of hypocalcemia largely manifest through neuromuscular excitability. Hypocalaemia can present acutely and be life threatening; early recognition and correction is critical. Quantitatively severe hypocalcemia can sometimes present with few symptoms, if onset has been protracted and chronic.

Pathophysiology

Calcium is one of the most abundant electrolytes in the body, and levels are tightly controlled by parathyroid hormone and vitamin D. Calcium is essential for cell function, cell membrane stability, neuronal transmission, bone physiology, blood homeostasis, and cell signaling.

Circulating calcium levels are impaired by several factors, but hypocalcemia is mainly secondary to the imbalance of calcium absorption, excretion, and distribution.

As 40% of circulating calcium is bound to albumin, in a ratio of 1 mg albumin to 0.8 mg calcium, measuring albumin is essential in interpreting total serum calcium levels. However, if ionized calcium is determined, there is no need to measure albumin or adjust the value of calcium concentration. Approximately 15% of circulating calcium is bound to sulfates, phosphates, lactate, and citrate, and the remaining 45% circulates as biologically active calcium in an ionized form.[1]

Signs and symptoms

Hypocalcemia varies from a mild asymptomatic biochemical abnormality to a life-threatening disorder. Acute hypocalcemia can lead to paresthesia, tetany, and seizures (characteristic physical signs may be observed, including Chvostek sign, which is neither sensitive nor specific for hypocalcemia, and Trousseau sign).[2] [3]Image

Papilledema, cataracts, basal ganglia calcifications, and skin, hair, and dental changes may occur with chronic hypocalcemia.[4] Neuropsychiatric manifestations include dementia in adults, anxiety, depression, lethargy, and extrapyramidal symptoms (parkinsonism).[4] [5] [6] Skin exam may show dermatitis, eczema, hyperpigmentation, psoriasis, brittle hair with patchy alopecia, and brittle nails with characteristic transverse grooves.Image Patients rarely may have congestive heart failure, angina, and hypotension.

Library

Carpopedal spasm (Trousseau sign) occurred a few minutes after inflation of a sphygmomanometer cuff above systolic blood pressure
Nail dystrophy due to hypocalcemia
Electrocardiogram (ECG) showing an adjusted QT interval (QTc) of 503 ms while in sinus rhythm

Citations

Key Articles

Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008 Jun 7;336(7656):1298-302.[Abstract][Full Text]
Turner J, Gittoes N, Selby P, et al. Society for endocrinology endocrine emergency guidance: emergency management of acute hypocalcaemia in adult patients. Endocr Connect. 2016 Sep;5(5):G7-8.[Abstract][Full Text]
Hannan FM, Thakker RV. Investigating hypocalcaemia. BMJ. 2013 May 9;346:f2213.

Referenced Articles

1. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008 Jun 7;336(7656):1298-302.[Abstract][Full Text]
2. Turner J, Gittoes N, Selby P, et al. Society for endocrinology endocrine emergency guidance: emergency management of acute hypocalcaemia in adult patients. Endocr Connect. 2016 Sep;5(5):G7-8.[Abstract][Full Text]
3. Jesus JE, Landry A. Images in clinical medicine. Chvostek's and Trousseau's signs. N Engl J Med. 2012 Sep 13;367(11):e15.[Abstract][Full Text]
4. Pepe J, Colangelo L, Biamonte F, et al. Diagnosis and management of hypocalcemia. Endocrine. 2020 Sep;69(3):485-95.[Abstract]
5. Maiti A, Chatterjee S. Neuropsychiatric manifestations and their outcomes in chronic hypocalcaemia. J Indian Med Assoc. 2013 Mar;111(3):174-7.[Abstract]
6. Hall A, Bin Farooq T, Alcaraz R Jr. Hypocalcemia-induced reversible psychosis. Cureus. 2022 Jan 2;14(1):e20874.[Abstract][Full Text]
7. Clarke BL, Brown EM, Collins MT, et al. Epidemiology and diagnosis of hypoparathyroidism. J Clin Endocrinol Metab. 2016 Jun;101(6):2284-99.[Abstract][Full Text]
8. De Sanctis V, Vullo C, Bagni B, et al. Hypoparathyroidism in beta-thalassemia major. Clinical and laboratory observations in 24 patients. Acta Haematol. 1992;88(2-3):105-8.[Abstract]
9. Carpenter TO, Carnes DL Jr, Anast CS. Hypoparathyroidism in wilson's disease. N Engl J Med. 1983 Oct 13;309(15):873-7.[Abstract]
10. Institute of Medicine. Dietary reference intakes for calcium and vitamin D. 2011 [internet publication].[Full Text]
11. Demay MB, Pittas AG, Bikle DD, et al. Vitamin D for the prevention of disease: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2024 Jul 12;109(8):1907-47.[Abstract][Full Text]
12. Ayuk J, Gittoes NJ. Contemporary view of the clinical relevance of magnesium homeostasis. Ann Clin Biochem. 2014 Mar;51(pt 2):179-88.[Abstract][Full Text]
13. Mantovani G, Bastepe M, Monk D, et al. Recommendations for diagnosis and treatment of pseudohypoparathyroidism and related disorders: an updated practical tool for physicians and patients. Horm Res Paediatr. 2020;93(3):182-96.[Abstract][Full Text]
14. Linglart A, Levine MA, Jüppner H. Pseudohypoparathyroidism. Endocrinol Metab Clin North Am. 2018 Dec;47(4):865-88.[Abstract][Full Text]
15. Tai YL, Shen HY, Nai WH, et al. Hungry bone syndrome after parathyroid surgery. Hemodial Int. 2023 Apr;27(2):134-45.[Abstract]
16. Witteveen JE, van Thiel S, Romijn JA, et al. Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol. 2013 Mar;168(3):R45-53.[Abstract]
17. Saxena R, Kumar S, Nafe Z, et al. Clinical, biochemical, and radiological correlation in the severity of acute pancreatitis: a retrospective study. Cureus. 2023 Feb 14;15(2):e34996.[Abstract][Full Text]
18. Smallridge RC, Wray HL, Schaaf M. Hypocalcemia with osteoblastic metastases in patient with prostate carcinoma. A cause of secondary hyperparathyroidism. Am J Med. 1981 Jul;71(1):184-8.[Abstract]
19. Murray RM, Grill V, Crinis N, et al. Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer. J Clin Endocrinol Metab. 2001 Sep;86(9):4133-8.[Abstract][Full Text]
20. Sadjadi SA, Pi A. Hyperphosphatemia, a cause of high anion gap metabolic acidosis: report of a case and review of the literature. Am J Case Rep. 2017 Apr 28;18:463-6.[Abstract][Full Text]
21. Perissinotti AJ, Bishop MR, Bubalo J, et al. Expert consensus guidelines for the prophylaxis and management of tumor lysis syndrome in the United States: results of a modified delphi panel. Cancer Treat Rev. 2023 Nov;120:102603.[Abstract]
22. Zheng WH, Yao Y, Zhou H, et al. Hyperphosphatemia and outcomes in critically ill patients: a systematic review and meta-analysis. Front Med (Lausanne). 2022 May 17;9:870637.[Abstract][Full Text]
23. Maalouf NM, Heller HJ, Odvina CV, et al. Bisphosphonate-induced hypocalcemia: report of three cases and review of literature. Endocr Pract. 2006 Jan-Feb;12(1):48-53.[Abstract]
24. Richmond BK. Profound refractory hypocalcemia after thyroidectomy in a patient receiving chronic oral bisphosphonate therapy. Am Surg. 2005 Oct;71(10):872-3.[Abstract]
25. Louie KS, Erhard C, Wheeler DC, et al. Cinacalcet-induced hypocalcemia in a cohort of European haemodialysis patients: predictors, therapeutic approaches and outcomes. J Nephrol. 2020 Aug;33(4):803-16.[Abstract][Full Text]
26. Zivin JR, Gooley T, Zager RA, et al. Hypocalcemia: a pervasive metabolic abnormality in the critically ill. Am J Kidney Dis. 2001 Apr;37(4):689-98.[Abstract]
27. Melchers M, van Zanten ARH. Management of hypocalcaemia in the critically ill. Curr Opin Crit Care. 2023 Aug 1;29(4):330-8.[Abstract][Full Text]
28. Prince MR, Erel HE, Lent RW, et al. Gadodiamide administration causes spurious hypocalcemia. Radiology. 2003 Jun;227(3):639-46.[Abstract]
29. Famularo G, Gasbarrone L, Minisola G. Hypomagnesemia and proton-pump inhibitors. Expert Opin Drug Saf. 2013 Sep;12(5):709-16.[Abstract]
30. Hess MW, Hoenderop JG, Bindels RJ, et al. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012 Sep;36(5):405-13.[Abstract][Full Text]
31. Lin LY, Smeeth L, Langan S, et al. Distribution of vitamin D status in the UK: a cross-sectional analysis of UK biobank. BMJ Open. 2021 Jan 6;11(1):e038503.[Abstract][Full Text]
32. Donzuso G, Mostile G, Nicoletti A, et al. Basal ganglia calcifications (fahr's syndrome): related conditions and clinical features. Neurol Sci. 2019 Nov;40(11):2251-63.[Abstract][Full Text]
33. Abu-Ain M, Aazem S, Morton C, et al. A rare potentially treatable cause of bilateral optic disc swelling. BMJ Case Rep. 2010 Oct 13;2010:bcr0320102835.[Abstract][Full Text]
34. Hannan FM, Thakker RV. Investigating hypocalcaemia. BMJ. 2013 May 9;346:f2213.
35. Hines OJ, Pandol SJ. Management of severe acute pancreatitis. BMJ. 2019 Dec 2;367:l6227.[Abstract][Full Text]
36. Tenner S, Vege SS, Sheth SG, et al. American College of Gastroenterology guidelines: management of acute pancreatitis. Am J Gastroenterol. 2024 Mar 1;119(3):419-37.[Abstract][Full Text]
37. Orloff LA, Wiseman SM, Bernet VJ, et al. American Thyroid Association statement on postoperative hypoparathyroidism: diagnosis, prevention, and management in adults. Thyroid. 2018 Jul;28(7):830-41.[Abstract][Full Text]
38. World Health Organization. Prevention and management of osteoporosis: report of a WHO scientific group. 2003 [internet publication].[Full Text]
39. National Institutes of Health. Health information: magnesium: fact sheet for health professionals. Jun 2022 [internet publication].[Full Text]
40. Rompianesi G, Hann A, Komolafe O, et al. Serum amylase and lipase and urinary trypsinogen and amylase for diagnosis of acute pancreatitis. Cochrane Database Syst Rev. 2017 Apr 21;4(4):CD012010.[Abstract][Full Text]
41. Leppäniemi A, Tolonen M, Tarasconi A, et al. 2019 WSES guidelines for the management of severe acute pancreatitis. World J Emerg Surg. 2019 Jun 13;14:27.[Abstract][Full Text]
42. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013 Jul-Aug;13(4 suppl 2):e1-15.[Abstract][Full Text]
43. American College of Radiology. ACR appropriateness criteria: acute pancreatitis. 2019 [internet publication].[Full Text]
44. Zeng W, Swee DS. Severe and refractory hypocalcaemia secondary to osteoblastic bone metastases in bladder signet ring carcinoma: a case report and literature review. Medicine (Baltimore). 2022 Jul 1;101(26):e29731.[Abstract][Full Text]