Q&A

Hypercalcemia: Common Yet Challenging

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Ultrasound of the neck may help to localize an enlarged parathyroid gland, especially if the scan is negative or equivocal.

Q: What are the complications of untreated hypercalcemia?

These include renal stones and urinary tract infections; peptic ulcer; altered mental status; pancreatitis; and during pregnancy, neonatal hypocalcemia.

Q: What is the medical treatment for hypercalcemia?

For acute hypercalcemia, use IV fluids at a high rate, such as normal saline 2,000 cc/hr, unless contraindicated.

Bisphosphonates, such as IV zoledronic acid, are potent inhibitors of bone resorption of calcium and can temporarily treat hypercalcemia, especially in cases of malignancy or severe hyperparathyroidism. It is important to know that oral bisphosphonates are not effective in treating hypercalcemia.

Avoid thiazide diuretics, as well as vitamin A, vitamin D, and calcium supplements. Another caveat: In the face of vitamin D deficiency, correct the vitamin D level to 40 to 60 ng/dL. Patients with 1,25(OH)2D-mediated hypercalcemia should be treated with glucocorticoids (prednisone or IV hydrocortisone), as they decrease 1,25(OH)2D.

Cinacalcet is approved for treatment of secondary hyperparathyroidism due to chronic renal failure, parathyroid carcinoma, and severe hypercalcemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy. The mode of action of cinacalcet is by binding to the parathyroid glands’ extracellular calcium-sensing receptors (CaSRs) to increase their affinity for extracellular calcium and decrease PTH secretion production.

Q: What are the indications for surgical intervention?

Surgery is recommended for patients with kidney stones or bone disease or with notable symptoms; those who have osteoporosis (identified on DXA scan); patients younger than 50; and those with a glomerular filtration rate below 60 mL/min and calcium 1.0 mg/dL or more above the upper limit of normal. Surgical removal of a parathyroid adenoma usually results in a cure.

Q: What causes secondary hyperparathyroidism?

Chronic renal failure is usually the cause. Hyperphosphatemia and decreased 1,25(OH)2D produce a decrease in ionized calcium. The parathyroid glands are thus stimulated and enlarge.

Vitamin D deficiency is another common cause; it is corrected with adequate vitamin D replacement. Once the vitamin D level is corrected, additional calcium supplementation should be given.

Q: What is the prognosis of hypercalcemia?

Primary hyperparathyroidism is usually chronic and progressive unless surgically cured or medically corrected. The prognosis of hypercalcemia is directly related to the degree of renal impairment or the underlying cause, such as malignancy. The presence of pancreatitis increases the mortality rate.

Regular monitoring and follow-up are important, especially if there is a trend of worsening hypercalcemia and etiology has not been identified. Monitor calcium and albumin at least every three months and renal function at least every six months.

Furthermore, check the 24-hour urine calcium and order DXA bone density testing annually.

SUGGESTED READING
American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons. AACE/AAES position statement on the diagnosis and management of primary hyperparathyroidism. Endocr Prac. 2005;11(1): 49-54.

McPhee SJ, Papadakis MA, eds. 2011 Current Medical Diagnosis and Treatment. McGraw Hill; 2011:1090-1097; 1098-1105; 1575-1579.

Jameson J, ed. Harrison’s Endocrinology. 2nd ed. McGraw Hill; 2010:367-378; 406-410; 411-442.

Brown SA. Hyperparathyroidism. In: Runge MS, Greganti MA, eds. Netter’s Internal Medicine. 2nd ed. Saunders; 2009:316-320.

Bilezikian JP, Khan AA, Potts JT Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Third International Workshop. J Clin Endocrinol Metab. 2009;94(2):335-339.

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