title: The association between fasting hypoglycemia and methylated mercaptopurine metabolites in children with acute lymphoblastic leukemia.
abstract: BACKGROUND
  Symptomatic fasting hypoglycemia has been reported as an unusual side effect in patients with acute lymphoblastic leukemia (ALL) on maintenance therapy. We evaluated the relation of the red cell 6-mercaptopurine (6-MP) metabolite 6-methyl-mercaptopurine (6MMP) with hypoglycemia.
  
  
  METHODS
  We retrospectively reviewed charts of three patients with ALL and symptomatic hypoglycemia while fasting who were noted to have high levels of 6MMP. All patients had an empiric trial of switching from evening to morning 6-MP administration, and two patients were subsequently switched to twice daily dosing. Patients also received complex carbohydrates at bedtime.
  
  
  RESULTS
  Switching 6-MP from evening to morning administration reduced 6MMP levels yet preserved adequate levels of the active metabolite red cell 6-thioguanine nucleotide (6TGN). All patients had decreased hypoglycemic events when changed from evening to morning dosing. Two patients showed a rebound in 6MMP levels with return of hypoglycemic symptoms. Both were then switched to twice daily 6-MP dosing with one having a decrease in 6MMP and hypoglycemic symptoms.
  
  
  CONCLUSIONS
  High levels of 6MMP are associated with symptomatic hypoglycemia which may be mitigated by switching to morning or twice daily 6-MP dose administration.
authors.affiliation: Pediatric Hematology/Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota.
authors.forename: Samyuktha
authors.initials: S
authors.lastname: Melachuri
authors.forename: Laura
authors.initials: L
authors.lastname: Gandrud
authors.forename: Bruce
authors.initials: B
authors.lastname: Bostrom
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001711:Biotransformation; D001786:Blood Glucose / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005215:Fasting / Q000097:blood*; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood*; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007003:Hypoglycemia / Q000139:chemically induced*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D007223:Infant; D008112:Liver Glycogen / Q000378:metabolism; D060046:Maintenance Chemotherapy; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008727:Methotrexate / Q000008:administration & dosage; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012189:Retrospective Studies; D013873:Thionucleotides / Q000097:blood*
chemical_list: D000964:Antimetabolites, Antineoplastic; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D006150:Guanine Nucleotides; D008112:Liver Glycogen; D011355:Prodrugs; D013873:Thionucleotides; C003964:6-thioguanylic acid; C010240:6-methylthiopurine; D003907:Dexamethasone; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D008727:Methotrexate
keywords: 6-mercaptopurine; 6MMP; ALL; ALT; hypoglycemia; thiopurine metabolites