What is the best workup for hypocalcemia?

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What is the best workup for hypocalcemia?

J Fam Pract. 2008 October;57(10):677-679

References

1. Fukugawa M, Kurokawa K. Calcium homeostasis and imbalance. Nephron. 2002;92(suppl 1):41-45.

2. Ruppe M. Hypocalcemia. In: American College of Physicians (ACP) Physician’s Information and Education Resource (PIER) database. Available at: http://pier.acponline.org/index.html. Accessed October 30, 2007.

3. Carlstedt F, Lind L. Hypocalcemic syndromes. Crit Care Clin. 2001;17:139, 53, vii-viii.

4. Centers for Disease Control and Prevention (CDC). Prevalence of chronic kidney disease and associated risk factors—United States, 1999-2004. MMWR Morb Mortal Wkly Rep. 2007;56:161-165.

5. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 suppl 3):S1-S201.

6. Rix M, Andreassen H, Eskildsen P, Langdahl B, Olgaard K. Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int. 1999;56:1084-1093.

7. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338:777-783.

8. Tangpricha V, Pearce EN, Chen TC, Holick MF. Vitamin D insufficiency among free-living healthy young adults. Am J Med. 2002;112:659-662.

9. Fardellone P, Sebert JL, Garabedian M, et al. Prevalence and biological consequences of vitamin D deficiency in elderly institutionalized subjects. Rev Rhum Engl Ed. 1995;62:576-581.

10. Hodkinson HM. Serum calcium in a geriatric inpatient population. Age Ageing. 1973;2:157-162.

11. 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. 1988;84:209-214.

12. Pattou F, Combemale F, Fabre S, et al. Hypocalcemia following thyroid surgery: incidence and prediction of outcome. World J Surg. 1998;22:718-724.

13. Guise TA, Mundy GR. Clinical review 69: evaluation of hypocalcemia in children and adults. J Clin Endocrinol Metab. 1995;80:1473-1478.

14. Hastbacka J, Pettila V. Prevalence and predictive value of ionized hypocalcemia among critically ill patients. Acta Anaesthesiol Scand. 2003;47:1264-1269.

Chronic kidney disease (66%) and vitamin D deficiency (24%) were the most common causes of hypocalcemia in a study of 594 elderly general medicine inpatients.¹⁰ In a study of 62 hypocalcemic patients in a medical intensive care unit, the cause of the hypocalcemia could be determined in only 28 (45%); most of the cases were caused by hypomagnesemia (28%), renal insufficiency (8%), and pancreatitis (3%).¹¹

TABLE
Causes of hypocalcemia by key test results

TEST RESULTS	COMMON CAUSES	LESS COMMON CAUSES
High PTH, high phosphorus	Renal failure	Pseudohypoparathyroidism (unresponsiveness to PTH) Other hyperphosphatemic states (eg, rhabdomyolysis or massive tumor lysis)
High PTH, low phosphorus	Vitamin D deficiency (with low bone calcium) caused by: inadequate diet or lack of sunlight gastrointestinal malabsorption, including drug-induced malabsorption (cholestyramine) hepatobiliary disease and hepatic drug metabolism pancreatitis	Blood transfusions (citrate) Bisphosphonates End organ unresponsiveness to vitamin D Congenital absence of renal vitamin D hydroxylase
Low PTH, high phosphorus	Hypoparathyroidism and hypomagnesemia	Thyroid and parathyroid surgery Autoimmune disorder (polyglandular syndrome) Hypothyroidism Damage to parathyroid gland from invasion or infiltration (eg, tumor) or radiation Inherited hypoparathyroidism
PTH, parathyroid hormone.

Serious causes of hypocalcemia

The usual cause of critically low serum calcium (<7 mg/dL “corrected” or <3.2 mg/dL ionized) is parathyroidectomy or acute renal failure. Hypocalcemia resulting from partial parathyroidectomy or thyroidectomy (with inadvertent parathyroidectomy) occurs in approximately 5% of these surgeries; 99.5% of cases resolve completely within a year.¹²

FAST TRACK

The most common causes of hypocalcemia:

renal failure
vitamin D deficiency
hypomagnesemia
pancreatitis
hypoparathyroidism

Recommendations

Several reviewers recommend a similar workup and differential diagnosis for hypocalcemia. Unfortunately, none cites quantitative data on the prevalence of hypocalcemia and its causes.^2,13

Some authors recommend measuring 25-OH vitamin D in all hypocalcemia patients with elevated PTH without hyperphosphatemia to confirm vitamin D deficiency.^1,2 Others emphasize the importance of measuring ionized calcium to detect hypocalcemia, especially in critically ill patients, in whom many acute variables can decrease ionized calcium (alkalosis can increase protein binding, for example).^1,3,14

Although several reviewers present an algorithmic approach to determining the cause of hypocalcemia,³ we could find no data on the derivation or validation of the diagnostic effectiveness of these algorithms.

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What is the best workup for hypocalcemia?

References

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