If calcium is elevated on a metabolic panel (usually done because the patient has hypertension or diabetes mellitus), I typically determine ionized calcium and parathyroid hormone (PTH) levels. If the ionized calcium is also elevated, should I add a parathyroid hormone-related protein (PTHrP) determination as well, even if I have no reason to suspect that malignancy is causing the hypercalcemia?
—Andrea L. Skaggs, MD, Lexington, Ky.

Ninety percent of the time, hypercalcemia is ultimately attributable to hyperparathyroidism or malignancy (J Bone Miner Res. 1991;6 Suppl 2:S51-S59). Although the PTH level in this patient is not reported, remember that up to 20% of patients with primary hyperparathyroidism have a serum PTH concentration at the upper end of the normal range. “Normal” is a misnomer here since the PTH is still inappropriately high in the presence of hypercalcemia and would be strongly suggestive of primary hyperparathyroidism. You are right to consider checking a PTHrP level next, but humoral hypercalcemia of malignancy is rarely present before clinically symptomatic malignancy. If both PTH and PTHrP levels are low, consider checking calcidiol and calcitriol levels to identify vitamin D intoxication or the extrarenal production of calcitriol seen in granulomatous diseases or lymphoma. If these diagnoses are suspected, a hydrocortisone suppression test may be helpful since hypercalcemia due to excess production of calcitriol will resolve during this test (Lancet. 1980;315:1320-1325). If PTH, PTHrP, and vitamin D levels are all low or normal, consider milk-alkali syndrome or a disorder of increased bone resorption, such as myeloma, thyrotoxicosis, or Paget’s disease.
—Daniel G. Tobin, MD (103-7)

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