FATAL PARATHYROID HORMONE-RELATED PROTEIN-INDUCED HUMORAL HYPERCALCEMIA OF MALIGNANCY IN A 3-MONTH-OLD INFANT

Parathyroid hormone-related protein (PTHrP) is the factor responsible for the syndrome of humoral hypercalcemia of malignancy (HHM). The syn drome is well documented in adult cancer patients, but has not previou sly 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 hepati c sarcoma. Parathyroid hormone (intact) levels were suppressed (7.5 pg /ml; normal 10-65). Fractional excretion of phosphate was markedly ele vated (73.5%; normal 8%-20%) as were urinary cAMP levels (12.48 nmol/d l 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.lpmol/l). Since previou s studies have demonstrated a potential role for PTHrP in the regulati on of embryonal tissue differentiation and transmembrane calcium flux, our observation of elevated PTHrP levels associated with the developm ent of a poorly differentiated hepatic sarcoma in a young infant may p rovide insight into the molecular mechanisms underlying HHM. We sugges t that serum or plasma PTHrP levels be determined in all children with hypercalcemia of malignancy in whom the hypercalcemia cannot otherwis e be explained.