title: Hypercalcemia of Malignancy and Colorectal Cancer.
abstract: Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control.
authors.affiliation: Icahn School of Medicine at Mount Sinai, Division of Endocrinology, Diabetes and Bone Diseases, Mount Sinai St. Luke's Hospital, 1111 Amsterdam Ave, Babcock Building 10th Floor, Room 1020, New York, NY 10025, USA.
authors.forename: Rodolfo J
authors.initials: RJ
authors.lastname: Galindo
authors.affiliation: Hofstra North-Shore LIJ School of Medicine, Division of Endocrinology Diabetes and Metabolism, 865 Northern Boulevard, Suite 203, Great Neck, NY 11021, USA.
authors.forename: Isabela
authors.initials: I
authors.lastname: Romao
authors.affiliation: Hofstra North-Shore LIJ School of Medicine, Division of Endocrinology Diabetes and Metabolism, 865 Northern Boulevard, Suite 203, Great Neck, NY 11021, USA.
authors.forename: Ageliki
authors.initials: A
authors.lastname: Valsamis
authors.affiliation: Hofstra North-Shore LIJ School of Medicine, Division of Endocrinology Diabetes and Metabolism, 865 Northern Boulevard, Suite 203, Great Neck, NY 11021, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Weinerman
authors.affiliation: Hofstra North-Shore LIJ School of Medicine, Division of Endocrinology Diabetes and Metabolism, 865 Northern Boulevard, Suite 203, Great Neck, NY 11021, USA.
authors.forename: Yael Tobi
authors.initials: YT
authors.lastname: Harris
keywords: Calcitriol; Colorectal cancer; Combined mechanism of hypercalcemia; Hypercalcemia; Parathyroid hormone-related peptide