Hypocalcemia: updates in diagnosis and management for primary care

Jeremy Fong, Aliya Khan, Jeremy Fong, Aliya Khan

Abstract

Objective: To provide family physicians with an evidence-based approach to the diagnosis and management of hypocalcemia. Quality of evidence MEDLINE and EMBASE articles from 2000 to 2010 were searched, with a focus on the diagnosis and management of hypocalcemia. Levels of evidence (I to III) were cited where appropriate, with most studies providing level II or III evidence. References of pertinent papers were also searched for relevant articles. Main message Chronic hypocalcemia is commonly due to inadequate levels of parathyroid hormone or vitamin D, or due to resistance to these hormones. Treatment focuses on oral calcium and vitamin D supplements, as well as magnesium if deficiency is present. Treatment can be further intensified with thiazide diuretics, phosphate binders, and a low-salt and low-phosphorus diet when treating hypocalcemia secondary to hypoparathyroidism. Acute and life-threatening calcium deficit requires treatment with intravenous calcium.The current treatment recommendations are largely based on expert clinical opinion and published case reports,as adequately controlled clinical trial data are not currently available. Complications of current therapies for hypoparathyroidism include hypercalciuria, nephrocalcinosis, renal impairment, and soft tissue calcification. Current therapy is limited by serum calcium fluctuations. Although these complications are well recognized, the effects of therapy on overall well-being, mood, cognition, and quality of life, as well as the risk of complications,have not been adequately studied.

Conclusion: Family physicians play a crucial role in educating patients about the long-term management and complications of hypocalcemia. Currently, management is suboptimal and marked by fluctuations in serum calcium and a lack of approved parathyroid hormone replacement therapy for hypoparathyroidism.

References

    1. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008;336(7656):1298–302.
    1. Murphy E, Williams GR. Hypocalcaemia. Medicine. 2009;37(9):465–8.
    1. Liamis G, Milionis HJ, Elisaf M. A review of drug-induced hypocalcemia. J Bone Miner Metab. 2009;27(6):635–42.
    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.
    1. Bilezikian JP, Khan A, Potts JT, Jr, Brandi ML, Clark BL, Shoback D, et al. Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res. 2011;26(10):2317–37. doi: 10.1002/jbmr.483.
    1. Walker Harris V, Jan De Beur S. Postoperative hypoparathyroidism: medical and surgical therapeutic options. Thyroid. 2009;19(9):967–73.
    1. Noto H, Heller HJ. Vitamin D deficiency as an ignored cause of hypocalcemia in acute illness: report of 2 cases and review of literature. Open Endocrinol J. 2009;3:1–4.
    1. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81(3):353–73.
    1. Mughal MZ, Salama H, Greenaway T, Laing I, Mawer EB. Lesson of the week: florid rickets associated with prolonged breast feeding without vitamin D supplementation. BMJ. 1999;318(7175):39–40.
    1. Rosen CJ, Brown S. Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med. 2003;348(15):1503–4.
    1. Peter R, Mishra V, Fraser WD. Severe hypocalcaemia after being given intravenous bisphosphonate. BMJ. 2004;328(7435):335–6.
    1. Mishra A, Wong L, Jonklaas J. Prolonged, symptomatic hypocalcemia with pamidronate administration and subclinical hypoparathyroidism. Endocrine. 2001;14(2):159–64.
    1. Yazbeck CF, Gonzalez-Angulo AM, Shaw SA, Waguespack SG, Vassilopoulou-Sellin R, Busaidy NL. Hypocalcemia induced by bisphophonates in cancer patients with vitamin D deficiency [2007 ASCO Annual Meeting abstract 19644] J Clin Oncol. 2007;25(18 Suppl):19644.
    1. Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y, et al. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2005;23(15):3314–21. Epub 2005 Feb 28.
    1. Khan A, Bilezikian J. Primary hyperparathyroidism: pathophysiology and impact on bone. CMAJ. 2000;163(2):184–7.
    1. Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med. 2008;359(4):391–403.
    1. Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med. 2000;343(25):1863–75.
    1. Maeda SS, Fortes EM, Oliveira UM, Borba VC, Lazaretti-Castro M. Hypoparathyroidism and pseudohypoparathyroidism. Arq Bras Endocrinol Metabol. 2006;50(4):664–73.
    1. Shiohara M, Shiozawa R, Kurata K, Matsuura H, Arai F, Yasuda T, et al. Effect of parathyroid hormone administration in a patient with severe hypoparathyroidism caused by gain-of-function mutation of calcium-sensing receptor. Endocr J. 2006;53(6):797–802. Epub 2006 Sep 19.
    1. Egbuna OI, Brown EM. Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations. Best Pract Res Clin Rheumatol. 2008;22(1):129–48.
    1. Herwadkar A, Gennery AR, Moran AS, Haeney MR, Arkwright PD. Association between hypoparathyroidism and defective T cell immunity in 22q11.2 deletion syndrome. J Clin Pathol. 2010;63(2):151–5.
    1. Botto LD, May K, Fernhoff PM, Correa A, Coleman K, Rasmussen SA, et al. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics. 2003;112(1 Pt 1):101–7.
    1. Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN. Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism. Hum Mutat. 2009;30(1):85–92.
    1. Urbano FL. Signs of hypocalcemia: Chvostek’s and Trousseau’s signs. Hosp Physician. 2000;36(3):43–5.
    1. Schaaf M, Payne CA. Effect of diphenylhydantoin and phenobarbital on overt and latent tetany. N Engl J Med. 1966;274(22):1228–33.
    1. Dickerson RN, Morgan LG, Cauthen AD, Alexander KH, Croce MA, Minard G, et al. Treatment of acute hypocalcemia in critically ill multiple-trauma patients. JPEN J Parenter Enteral Nutr. 2005;29(6):436–41.
    1. Dickerson RN, Henry NY, Miller PL, Minard G, Brown RO. Low serum total calcium concentration as a marker of low serum ionized calcium concentration in critically ill patients receiving specialized nutrition support. Nutr Clin Pract. 2007;22(3):323–8.
    1. Dickerson RN, Alexander KH, Minard G, Croce MA, Brown RO. Accuracy of methods to estimate ionized and “corrected” serum calcium concentrations in critically ill multiple trauma patients receiving specialized nutrition support. JPEN J Parenter Enteral Nutr. 2004;28(3):133–41.
    1. Dickerson RN. Treatment of hypocalcemia in critical illness—part 1. Nutrition. 2007;23(4):358–61.
    1. Tohme JF, Bilezikian JP. Diagnosis and treatment of hypocalcemic emergencies. Endocrinologist. 1996;6(1):10–8.
    1. Body JJ, Bouillon R. Emergencies of calcium homeostasis. Rev Endocr Metab Disord. 2003;4(2):167–75.
    1. Harvey JA, Zobitz MM, Pak CY. Dose dependency of calcium absorption: a comparison of calcium carbonate and calcium citrate. J Bone Miner Res. 1988;3(3):253–8.
    1. Eryol NK, Colak R, Ozdoğru I, Tanriverdi F, Unal S, Topsakal R, et al. Effects of calcium treatment on QT interval and QT dispersion in hypocalcemia. Am J Cardiol. 2003;91(6):750–2.
    1. Hopper AD, Hadjivassiliou M, Butt S, Sanders DS. Adult coeliac disease. BMJ. 2007;335(7619):558–62.
    1. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet. 1998;351(9105):805–6.
    1. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77(1):204–10.
    1. Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF. Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Am J Clin Nutr. 2003;77(6):1478–83.
    1. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387–91.
    1. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998;68(4):854–8.
    1. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326(7387):469.
    1. Bouillon R, Norman AW, Lips P. Vitamin D deficiency. N Engl J Med. 2007;357(19):1980–1.
    1. Noordzij M, Voormolen NM, Boeschoten EW, Dekker FW, Bos WJ, Krediet RT, et al. Disordered mineral metabolism is not a risk factor for loss of residual renal function in dialysis patients. Nephrol Dial Transplant. 2009;24(5):1580–7.
    1. Horwitz MJ, Stewart AF. Hypoparathyroidism: is it time for replacement therapy? J Clin Endocrinol Metab. 2008;93(9):3307–9.
    1. Arlt W, Fremerey C, Callies F, Reincke M, Schneider P, Timmermann W, et al. Well-being, mood and calcium homeostasis in patients with hypoparathyroidism receiving standard treatment with calcium and vitamin D. Eur J Endocrinol. 2002;146(2):215–22.
    1. Winer KK, Yanovski JA, Cutler GB., Jr Synthetic human parathyroid hormone 1–34 vs calcitriol and calcium in the treatment of hypoparathyroidism. JAMA. 1996;276(8):631–6.
    1. Winer KK, Yanovski JA, Sarani B, Cutler GB., Jr A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1–34 in treatment of hypoparathyroidism. J Clin Endocrinol Metab. 1998;83(10):3480–6.
    1. Winer KK, Ko CW, Reynolds JC, Dowdy K, Keil M, Peterson D, et al. Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1–34) versus calcitriol and calcium. J Clin Endocrinol Metab. 2003;88(9):4214–20.
    1. Winer KK, Sinaii N, Peterson D, Sainz B, Jr, Cutler GB., Jr Effects of once versus twice-daily parathyroid hormone 1–34 therapy in children with hypoparathyroidism. J Clin Endocrinol Metab. 2008;93(9):3389–95. Epub 2008 May 20.
    1. Winer KK, Sinaii N, Reynolds J, Peterson D, Dowdy K, Cutler GB., Jr Long-term treatment of 12 children with chronic hypoparathyroidism: a randomized trial comparing synthetic human parathyroid hormone 1–34 versus calcitriol and calcium. J Clin Endocrinol Metab. 2010;95(6):2680–8. Epub 2010 Apr 14.
    1. Rubin MR, Sliney J, Jr, McMahon DJ, Silverberg SJ, Bilezikian JP. Therapy of hypoparathyroidism with intact parathyroid hormone. Osteoporos Int. 2010;21(11):1927–34. Epub 2010 Jan 22.
    1. Rubin MR, Bilezikian JP. Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement. Arq Bras Endocrinol Metabol. 2010;54(2):220–6.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅