Octreotide Therapy for Tumor-Induced Osteomalacia

Abstract

UMOR-induced osteomalacia (also known as oncogenic osteomalacia) 1 is a rare disorder characterized by phosphaturia, hypophospha-temia, and osteomalacia mimicking the clinical phenotype of either X-linked 2 or autosomal dominant 3 hereditary hypophosphatemic rickets. Tumor-induced osteomalacia develops because of tumors that are predominantly of benign mesenchymal origin 4 but that may occasionally be malignant, as was recently reported. 5 Surgical removal of the tumor relieves all symptoms. Hemangiopericytoma is the most dominant histologic entity in tumor-induced osteomala-cia. 4,6 Paraneoplastic secretion by the tumor of an unknown factor or factors-termed "phospha-tonins"-causing renal tubular phosphate wasting has been proposed as the pathogenic mechanism. 7 We describe an adult man who had hypophos-phatemic osteomalacia for several years before an oc-treotide scan revealed a mesenchymal tumor in his left thigh. Moreover, subcutaneous administration of octreotide, a synthetic somatostatin analogue, abolished renal tubular phosphate wasting before subsequent surgical removal of the tumor. CASE REPORT A 50-year-old man presented with chronic pain of the spine, ribs, femurs, and tibias. The clinical examination was otherwise normal. There was no family history of metabolic bone disease. The initial evaluation in July 1997 revealed elevated urinary phosphorus excretion, low serum phosphorus levels, and elevated serum alkaline phosphatase and osteocalcin levels. The serum values for calcium, parathyroid hormone, 25-hydroxyvitamin D 3 , and calcitonin were normal; the serum value for 1,25-dihydroxy-T vitamin D 3 was inappropriately low (6.9 pg per milliliter; normal range, 35 to 80). The diagnostic evaluation at this time provided no evidence of tumor. Multiple rib fractures were identified. A bone scan with technetium-99m-labeled 2,3-dicarboxypropane-1,1-diphosphonate showed a pattern of focal, late-phase enhancement in the spine and ribs; this was suggestive of metabolic bone disease. The patient was given the diagnosis of idiopathic hypophos-phatemic osteomalacia with renal phosphate wasting. Continuous oral supplementation with phosphate and 1,25-dihydroxyvitamin D 3 (1.25 µg per day) was initiated. Three years after the initial diagnosis , progressive metabolic bone disease prompted another extensive evaluation. METHODS Assays Serum, plasma, and urinary constituents were measured by standard techniques. Hormone measurements were performed with the use of commercial immunoassay kits. Assays of serum parathyroid hormone, 25-hydroxyvitamin D 3 , 1,25-dihydroxyvitamin D 3 , and calcitonin were performed with commercial kits (DPC Biermann, Bad Nauheim, Germany), as were those for osteocalcin (Diagnos-tic Systems Laboratories, Sinsheim, Germany) and urinary type I collagen C-telopeptides (Beckmann Coulter, Krefeld, Germany). For calculation of renal clearance of phosphate, serum and urinary concentrations of phosphorus were determined together with the excreted urinary volume during two one-hour collection periods (Table 1). Values for the threshold for renal tubular reabsorption of phosphate were derived from the nomogram provided by Walton and Bijvoet. 8 The excreted urinary volume was quantified during a two-hour collection period in the morning, and urinary phosphate and creatinine levels were determined.