title: Sunitinib-induced hyperparathyroidism: a possible mechanism to altered bone homeostasis.
abstract: BACKGROUND
  Sunitinib malate is an orally bioavailable tyrosine kinase inhibitor that is active against many tyrosine kinase receptors involving crucial pathways in both healthy tissues and malignant tissues. Because its use in clinical practice is quite recent, many of its possible side effects remain unknown. In this report, the authors describe the incidence of new-onset hyperparathyroidism in a cohort of patients with metastatic renal cell carcinoma who received treatment with sunitinib.
  
  
  METHODS
  Twenty-six patients who received first-line sunitinib for metastatic renal cell carcinoma were enrolled in this study for a mineral and parathyroid function assessment. Plasma levels of intact parathyroid hormone; serum levels of calcium, phosphorus, 25-hydroxyvitamin D(3), and 1,25-dihydrovitamin D(3); and urinary 24-hour calcium and phosphorus excretion all were measured in each patient. Biochemical evaluations were performed before the beginning of treatment and at the end of each sunitinib treatment period.
  
  
  RESULTS
  Eighteen of 26 patients (69.2%) developed hyperparathyroidism with normal serum calcium levels, and 6 of them developed hypophosphatemia. Patients presented with a mean elevation of parathyroid hormone after 2.2 cycles of sunitinib. The levels of 25-OH vitamin D(3) were stable over the course of treatment, whereas 1,25-OH vitamin D(3) levels were increased in 5 hyperparathyroid patients. Those who presenting with elevated parathyroid hormone levels had low or undetectable urinary calcium levels. Parathyroid hormone elevation usually persisted but did not progress during long-term therapy with sunitinib. Permanent treatment interruption resulted in a resolution of hyperparathyroidism.
  
  
  CONCLUSIONS
  Hyperparathyroidism developed in an high percentage of patients on sunitinib. Therefore, the authors concluded that sunitinib may affect parathyroid function and bone mineral homeostasis, possibly resulting in abnormal bone remodeling.
authors.affiliation: Second Medical Oncology Unit, Careggi University Hospital, Florence University, Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Baldazzi
authors.forename: Renato
authors.initials: R
authors.lastname: Tassi
authors.forename: Alberto
authors.initials: A
authors.lastname: Lapini
authors.forename: Alice
authors.initials: A
authors.lastname: Lunghi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Garofoli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Caruso
authors.forename: Marco
authors.initials: M
authors.lastname: Carini
authors.forename: Roberto
authors.initials: R
authors.lastname: Mazzanti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001842:Bone and Bones / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000139:chemically induced* / Q000453:epidemiology; D017674:Hypophosphatemia / Q000139:chemically induced; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects*; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D002118:Calcium; D000077210:Sunitinib