title: Hypercalcemia secondary to gastrointestinal stromal tumors: parathyroid hormone-related protein independent mechanism?
abstract: OBJECTIVE
  Hypercalcemia is a common paraneoplastic manifestation of many malignancies like breast, ovarian, and squamous-cell cancers of head and neck; however, there have been only a few case reports of hypercalcemia associated with gastrointestinal stromal tumors (GISTs). We report a case of GIST presenting with hypercalcemia without any osseous metastasis and provide a literature review regarding the mechanisms of hypercalcemia and therapeutic strategies.
  
  
  METHODS
  We present a report of case and a review of the relevant literature.
  
  
  RESULTS
  A 52-year-old woman with history of localized breast cancer in remission and a pelvic 13 × 12 cm GIST with peritoneal, liver, and lung metastases presented with hypercalcemia of 14.3 mg/dL (8.5-10.5 mg/dL). Parathyroid hormone-related protein (PTHrP) was undetectable, intact parathyroid hormone (PTH) was appropriately low at 1 pg/mL (10-65 pg/mL), and 1,25 dihydroxy vitamin D (1,25 OH2 vit D) was elevated at 131 pg/mL (18-78 pg/mL) with normal renal function. Calcium responded transiently to tyrosine kinase inhibitor therapy and bisphosphonates but within a year, she expired due to tumor progression.
  
  
  CONCLUSIONS
  GIST is a rare cause of hypercalcemia. In addition to PTHrP expression, direct tumor production of 1,25(OH)2 vit D or 1-α hydroxylase enzyme resulting in activation of 25-hydroxy vitamin D may be an alternative mechanism in GIST-related hypercalcemia. Therapy with tyrosine kinase inhibitors and bisphosphonates is recommended, though prognosis is poor. Further investigations are needed to characterize the etiology and management of hypercalcemia in these patients.
authors.affiliation: Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Prathima
authors.initials: P
authors.lastname: Jasti
authors.forename: Vipul Tulsi
authors.initials: VT
authors.lastname: Lakhani
authors.forename: Alison
authors.initials: A
authors.lastname: Woodworth
authors.forename: Kathryn McCrystal
authors.initials: KM
authors.lastname: Dahir
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications / Q000473:pathology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism; D004164:Diphosphonates / Q000627:therapeutic use; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017809:Fatal Outcome; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000150:complications*; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology*; D000068877:Imatinib Mesylate; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000097:blood / Q000502:physiology*; D010879:Piperazines / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004791:Enzyme Inhibitors; D044162:Parathyroid Hormone-Related Protein; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D002117:Calcitriol; D002118:Calcium