Fatal parathyroid hormone-related protein-induced humoral hypercalcemia of malignancy in a 3-month-old infant.

Abstract

Parathyroid hormone-related protein (PTHrP) is the factor responsible for the syndrome of humoral hypercalcemia of malignancy (HHM). The syndrome is well documented in adult cancer patients, but has not previously been described in young children. We report the case of a 3-month-old infant who developed refractory hypercalcemia (peak total calcium 13.8 mg/dl; normal 8.5-10.5, ionized calcium 3.3 meq/l; normal 2.0-2.5) associated with a high-grade, poorly differentiated malignant hepatic sarcoma. Parathyroid hormone (intact) levels were suppressed (7.5 pg/ml; normal 10-65). Fractional excretion of phosphate was markedly elevated (73.5%; normal 8%-20%) as were urinary cAMP levels (12.48 nmol/dl glomerular filtrate; normal 1.83-4.47) suggesting a PTH-like effect. Increased levels of PTHrP were present both in the serum (4.9 pmol/l; normal for adults < 1.5) and ascitic fluid (6.1 pmol/l). Since previous studies have demonstrated a potential role for PTHrP in the regulation of embryonal tissue differentiation and transmembrane calcium flux, our observation of elevated PTHrP levels associated with the development of a poorly differentiated hepatic sarcoma in a young infant may provide insight into the molecular mechanisms underlying HHM. We suggest that serum or plasma PTHrP levels be determined in all children with hypercalcemia of malignancy in whom the hypercalcemia cannot otherwise be explained.