Hypocalcemia Workup

  • Author: Manish Suneja, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Oct 27, 2011
 

Approach Considerations

Symptomatic patients with classic clinical findings of acute hypocalcemia require immediate resuscitation and evaluation. However, most cases of hypocalcemia are discovered by clinical suspicion and appropriate laboratory testing. Albumin, liver function studies, and coagulation parameters should be obtained to assess liver dysfunction and hypoalbuminemia. Blood urea nitrogen (BUN) and serum creatinine should be measured, as elevated levels may indicate renal dysfunction.

In a patient with hypocalcemia, measurement of the serum albumin is essential to distinguish true hypocalcemia, which involves a reduction in ionized serum calcium, from factitious hypocalcemia, meaning decreased total, but not ionized, calcium. To correct for hypoalbuminemia, subtract 0.8 mg/dL from the total serum calcium for each 1.0 g/dL decrease in albumin below 4.0 g/dL.

The parathyroid hormone (PTH) level should be checked as early as possible. Vitamin D should be measured if deficiency is suspected. In patients with PTH deficiencies, alkaline phosphatase levels tend to be normal or slightly decreased, whereas these levels frequently are elevated in patients with osteomalacia and rickets. If the diagnosis of osteomalacia is suspected, a bone biopsy can determine the final diagnosis.

An electrocardiogram (ECG) is indicated. Imaging studies may include plain radiography or computed tomography (CT) scans. On radiographs, disorders associated with rickets or osteomalacia present with the pathognomonic Looser zones, which are better observed in the pubic ramus, upper femoral bone, and ribs. Radiography will also disclose osteoblastic metastases from certain tumors (eg, breast, prostate, lung), which can cause hypocalcemia. CT scans of the head may show basal ganglia calcification and extrapyramidal neurologic symptoms (in idiopathic hypoparathyroidism).

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Serum Ionized Calcium

Ionized calcium is the definitive method for diagnosing hypocalcemia. A serum calcium level less than 8.5 mg/dL or an ionized calcium level less than 1.0 mmol/L is considered hypocalcemia.

Analysis for the ionized calcium level must be performed rapidly with whole blood to avoid changes in pH and anion chelation. Blood should be drawn in an unheparinized syringe for best results.

Falsely elevated calcium levels may be seen with elevated acetaminophen levels, alcohol, hydralazine, and hemolysis. Falsely depressed levels can be seen with heparin, oxalate, citrate, or hyperbilirubinemia.

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Serum Electrolytes

In healthy kidneys, parathyroid hormone (PTH) stimulates phosphate excretion. The combination of hypocalcemia and elevated phosphorus levels typically suggests hypoparathyroidism or pseudohypoparathyroidism.

Patients with renal failure and hypocalcemia usually present with hyperphosphatemia and high PTH levels. Hypophosphatemia develops in patients with vitamin D deficiency and hungry bone disease.

The serum magnesium level should always be checked to determine its potential contribution to the hypocalcemia. Occasionally, inadequate dietary magnesium intake leads to hypomagnesemia, hypophosphatemia, and hypocalcemia.

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Parathyroid Hormone

The parathyroid hormone level should be checked as early as possible. This test is an antibody-mediated radioimmunoassay. Low-to-normal PTH levels occur in patients with hereditary or acquired hypoparathyroidism and in patients with severe hypomagnesemia.

Patients with ineffective PTH have elevated PTH levels. The PTH elevation is a result of hypocalcemia.

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Vitamin D Metabolites

If vitamin D deficiency is suspected, measurements of 25(OH) D and 1,25(OH)2 D should be performed. A low 25(OH) D level suggests vitamin D deficiency from poor nutritional intake, lack of sunlight, or malabsorption. Low levels of 1,25(OH)2 D in association with high PTH suggest ineffective PTH from a lack of vitamin D, as observed in patients with chronic renal failure, vitamin D–dependent rickets type I (VDDR-I), and pseudohypoparathyroidism.

Urinary cyclic adenosine monophosphate (cAMP) may help differentiate hypoparathyroidism from pseudohypoparathyroidism types I and II. Urinary cAMP levels are generally elevated in hypoparathyroidism.

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Electrocardiogram

Acute hypocalcemia causes prolongation of the QT interval, which may lead to ventricular dysrhythmias (see the image below). It also causes decreased myocardial contractility, which can lead to heart failure, hypotension, and angina. Cardiomyopathy and ventricular tachycardia may be reversible with treatment.

Electrocardiogram (ECG) findings in severe hypocalElectrocardiogram (ECG) findings in severe hypocalcemia.
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Contributor Information and Disclosures
Author

Manish Suneja, MD  Assistant Professor, Department of Internal Medicine, Division of Nephrology, University of Iowa Hospitals and Clinics

Manish Suneja, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology, and National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Heather A Muster  MD, MS, Medical Director

Heather A Muster is a member of the following medical societies: American College of Physicians, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Minnesota Medical Association, and National Kidney Foundation

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

Additional Contributors

Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Christopher B Beach, MD, FACEP, FAAEM Associate Professor and Vice Chair of Emergency Medicine, Department of Emergency Medicine, Associate Professor of Institute for Healthcare Studies, Institute for Patient Safety, Feinberg School of Medicine, Northwestern University

Christopher B Beach, MD, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Robin R Hemphill, MD, MPH Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University

Robin R Hemphill, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Dept of Veterans Affairs Grant/research funds Research

James W Lohr, MD Professor, Department of Internal Medicine, Division of Nephrology, Fellowship Program Director, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research

Disclosure: Genzyme Honoraria Speaking and teaching

Alfredo A Pegoraro, MD Consulting Staff, Nephrology Associates

Alfredo A Pegoraro, MD is a member of the following medical societies: American Medical Assocation, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

  1. Levine BA, Williams RP. Calcium binding to proteins and other large biological anion centers. Academic Press. 1982;II:1.

  2. Pedersen KO. Binding of calcium to serum albumin. I. Stoichiometry and intrinsic association constant at physiological pH, ionic strength, and temperature. Scand J Clin Lab Invest. Dec 1971;28(4):459-69. [Medline].

  3. Sarko J. Bone and mineral metabolism. Emerg Med Clin North Am. Aug 2005;23(3):703-21, viii. [Medline].

  4. Hofer AM, Brown EM. Extracellular calcium sensing and signalling. Nat Rev Mol Cell Biol. Jul 2003;4(7):530-8. [Medline].

  5. Mundy GR, Guise TA. Hormonal control of calcium homeostasis. Clin Chem. Aug 1999;45(8 Pt 2):1347-52. [Medline].

  6. Silver J, Yalcindag C, Sela-Brown A, Kilav R, Naveh-Many T. Regulation of the parathyroid hormone gene by vitamin D, calcium and phosphate. Kidney Int Suppl. Dec 1999;73:S2-7. [Medline].

  7. Yamamoto M, Kawanobe Y, Takahashi H, Shimazawa E, Kimura S, Ogata E. Vitamin D deficiency and renal calcium transport in the rat. J Clin Invest. Aug 1984;74(2):507-13. [Medline].

  8. Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med. Jul 24 2008;359(4):391-403. [Medline].

  9. Burch WM, Posillico JT. Hypoparathyroidism after I-131 therapy with subsequent return of parathyroid function. J Clin Endocrinol Metab. Aug 1983;57(2):398-401. [Medline].

  10. Cruz DN, Perazella MA. Biochemical aberrations in a dialysis patient following parathyroidectomy. Am J Kidney Dis. May 1997;29(5):759-62. [Medline].

  11. Looker AC, Dawson-Hughes B, Calvo MS, Gunter EW, Sahyoun NR. Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone. May 2002;30(5):771-7. [Medline].

  12. Linnebur SA, Vondracek SF, Vande Griend JP, Ruscin JM, McDermott MT. Prevalence of vitamin D insufficiency in elderly ambulatory outpatients in Denver, Colorado. Am J Geriatr Pharmacother. Mar 2007;5(1):1-8. [Medline].

  13. Barone A, Giusti A, Pioli G, Girasole G, Razzano M, Pizzonia M, et al. Secondary hyperparathyroidism due to hypovitaminosis D affects bone mineral density response to alendronate in elderly women with osteoporosis: a randomized controlled trial. J Am Geriatr Soc. May 2007;55(5):752-7. [Medline].

  14. Beckerman P, Silver J. Vitamin D and the parathyroid. Am J Med Sci. Jun 1999;317(6):363-9. [Medline].

  15. Johnson JM, Maher JW, DeMaria EJ, Downs RW, Wolfe LG, Kellum JM. The long-term effects of gastric bypass on vitamin D metabolism. Ann Surg. May 2006;243(5):701-4; discussion 704-5. [Medline].

  16. Brasier AR, Nussbaum SR. Hungry bone syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med. Apr 1988;84(4):654-60. [Medline].

  17. Dettelbach MA, Deftos LJ, Stewart AF. Intraperitoneal free fatty acids induce severe hypocalcemia in rats: a model for the hypocalcemia of pancreatitis. J Bone Miner Res. Dec 1990;5(12):1249-55. [Medline].

  18. Szczech LA. The impact of calcimimetic agents on the use of different classes of phosphate binders: results of recent clinical trials. Kidney International. 2004;90:S46-48.

  19. Kido Y, Okamura T, Tomikawa M, Yamamoto M, Shiraishi M, Okada Y. Hypocalcemia associated with 5-fluorouracil and low dose leucovorin in patients with advanced colorectal or gastric carcinomas. Cancer. Oct 15 1996;78(8):1794-7. [Medline].

  20. Recker RR, Lewiecki EM, Miller PD, Reiffel J. Safety of bisphosphonates in the treatment of osteoporosis. Am J Med. Feb 2009;122(2 Suppl):S22-32. [Medline].

  21. Stamp TC, Round JM, Rowe DJ, Haddad JG. Plasma levels and therapeutic effect of 25-hydroxycholecalciferol in epileptic patients taking anticonvulsant drugs. Br Med J. Oct 7 1972;4(5831):9-12. [Medline].

  22. Dykes C, Cash BD. Key safety issues of bowel preparations for colonoscopy and importance of adequate hydration. Gastroenterol Nurs. Jan-Feb 2008;31(1):30-5; quiz 36-7. [Medline].

  23. Niemeijer ND, Rijk MC, van Guldener C. Symptomatic hypocalcemia after sodium phosphate preparation in an adult with asymptomatic hypoparathyroidism. Eur J Gastroenterol Hepatol. Apr 2008;20(4):356-8. [Medline].

  24. Lier H, Krep H, Schroeder S, Stuber F. Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia, anemia, and hypothermia on functional hemostasis in trauma. J Trauma. Oct 2008;65(4):951-60. [Medline].

  25. Desai TK, Carlson RW, Geheb MA. Prevalence and clinical implications of hypocalcemia in acutely ill patients in a medical intensive care setting. Am J Med. Feb 1988;84(2):209-14. [Medline].

  26. Zivin JR, Gooley T, Zager RA, Ryan MJ. Hypocalcemia: a pervasive metabolic abnormality in the critically ill. Am J Kidney Dis. Apr 2001;37(4):689-98. [Medline].

  27. Forsythe RM, Wessel CB, Billiar TR, Angus DC, Rosengart MR. Parenteral calcium for intensive care unit patients. Cochrane Database Syst Rev. 2008;(4):CD006163. [Medline].

  28. Russell CF, Edis AJ. Surgery for primary hyperparathyroidism: experience with 500 consecutive cases and evaluation of the role of surgery in the asymptomatic patient. Br J Surg. May 1982;69(5):244-7. [Medline].

  29. Hurley K, Baggs D. Hypocalcemic cardiac failure in the emergency department. J Emerg Med. Feb 2005;28(2):155-9. [Medline].

  30. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. Jun 7 2008;336(7656):1298-302. [Medline].

  31. Kaye M, Somerville PJ, Lowe G, Ketis M, Schneider W. Hypocalcemic tetany and metabolic alkalosis in a dialysis patient: an unusual event. Am J Kidney Dis. Sep 1997;30(3):440-4. [Medline].

  32. Eraut D. Idiopathic hypoparathyroidism presenting as dementia. Br Med J. Mar 9 1974;1(5905):429-30. [Medline].

  33. Murphy G, Bartle S. Hypocalcemic laryngospasm and tetany in a child with renal dysplasia. Pediatr Emerg Care. Jul 2006;22(7):507-9. [Medline].

  34. Soffer D, Licht A, Yaar I, Abramsky O. Paroxysmal choreoathetosis as a presenting symptom in idiopathic hypoparathyroidism. J Neurol Neurosurg Psychiatry. Jul 1977;40(7):692-4. [Medline].

  35. Doorenbos CJ, Ozyilmaz A, van Wijnen M. Severe pseudohypocalcemia after gadolinium-enhanced magnetic resonance angiography. N Engl J Med. Aug 21 2003;349(8):817-8. [Medline].

  36. Mark PB, Mazonakis E, Shapiro D, Spooner RJ, Stuart C Rodger R. Pseudohypocalcaemia in an elderly patient with advanced renal failure and renovascular disease. Nephrol Dial Transplant. Jul 2005;20(7):1499-500. [Medline].

  37. Prince MR, Choyke PL, Knopp MV. More on pseudohypocalcemia and gadolinium-enhanced MRI. N Engl J Med. Jan 1 2004;350(1):87-8; author reply 87-8. [Medline].

  38. Jung RT, Davie M, Hunter JO, Chalmers TM. Ultraviolet light: an effective treatment of osteomalacia in malabsorption. Br Med J. Jun 24 1978;1(6128):1668-9. [Medline].

  39. Norman JG, Politz DE. Safety of immediate discharge after parathyroidectomy: a prospective study of 3,000 consecutive patients. Endocr Pract. Mar-Apr 2007;13(2):105-13. [Medline].

 
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Electrocardiogram (ECG) findings in severe hypocalcemia.
 
 
 
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