allopurinol and Hypoglycemia

Topics: Acidosis; Acute Kidney Injury; Allopurinol; Aluminum Hydroxide; Burkitt Lymphoma; Child; Humans; Hypercalcemia; Hyperlipidemias; Hypertension, Renal; Hypoglycemia; Lymphoma; Male; Mannitol; Metabolic Diseases; Phosphorus Metabolism Disorders; Uric Acid; Xanthines

Fasting hypoglycemia is a known complication of mercaptopurine (6MP) maintenance therapy for acute lymphoblastic leukemia (ALL). It is associated with high levels of the methylated metabolite 6-methyl-mercaptopurine (6MMP). Symptoms of hypoglycemia include morning tremulousness, nausea and vomiting. We have previously shown that switching 6MP dosing from evening to morning resolved hypoglycemia by reducing 6MMP; however, the reduction of 6MMP was only transient, potentially resulting in return of hypoglycemia. In children and adults with Crohn's disease, co-prescribing allopurinol with 6MP blocks the activity of thiopurine methytransferase (TPMT), reducing 6MMP and improving its tolerance. As a consequence of inhibiting TPMT, 6MP is shunted toward the production of 6-thioguanine nucleotide (6TGN), which will result in pancytopenia if the dose of 6MP is not reduced. We demonstrate that allopurinol with a reduced dose of 6MP in two patients with ALL and 6MMP-associated hypoglycemia resulted in a complete and sustained suppression of 6MMP and rapid reversal of hypoglycemia and its symptoms.

Topics: Allopurinol; Antimetabolites, Antineoplastic; Blood Glucose; Blood Glucose Self-Monitoring; Child; Child, Preschool; Enzyme Inhibitors; Female; Humans; Hypoglycemia; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Skewing of mercaptopurine (6-MP) metabolism preferentially toward the 6-methylmercaptopurine (6-MMP) metabolite over the antileukemic metabolite 6-thioguanine (6-TGN) is associated with 6-MP-related hepatotoxocity. Allopurinol when coadministered with 6-MP can reduce this skewing and ameliorate the associated adverse effects. The cases we report here demonstrate that aberrant overproduction of 6-MMP is also associated with profound 6-MP-associated hypoglycemia, which can be reversed by administration of allopurinol. This case series contributes to the scant literature on 6-MP-induced hypoglycemia and provides evidence that addition of allopurinol to reduced dose 6-MP can successfully manage this severe toxicity.

Topics: Allopurinol; Child; Female; Humans; Hypoglycemia; Male; Mercaptopurine; Thioguanine

University of Wisconsin (UW) solution (Viaspan) is currently used to preserve organs from nonheartbeating donors. Histidine-tryptophan-ketoglutarate (HTK) solution (Custodiol) is of proven efficacy in experimental pancreas preservation, but its efficacy in combined warm ischemia (WI) and cold ischemia (CI) is unknown. The viability of HTK-preserved porcine pancreatic grafts was assessed after various periods of WI and compared with grafts flushed and preserved with UW solution.. A total of 14 pigs were used: G1 (n=4, UW) and G2 (n=4, HTK) with 15-min WI and 16-hr cold storage; G3 (n=3, UW) and G4 (n=3, HTK) with 30-min WI and 16-hr cold storage.. All animals in G1 and G2 were normoglycemic, whereas only 66% of pancreases were functioning in G3 and G4. HTK perfusion was associated with increased wet weight. Transient hyperinsulinemia was noted in all the groups on postoperative day 1 (mean range: 8.9-12.4 microU/L). Postoperative serum amylase and lipase were more pronounced in G3 and G4. However, HTK-stored grafts exhibited less evidence of biochemical pancreatitis as compared with UW-stored grafts on the first postoperative day in the group with 15-min WI. Mean K values of intravenous glucose tolerance tests on postoperative day 14 were similar in both groups. Vascular congestion was uniformly observed and was considered a typical feature of WI.. Porcine pancreatic grafts are viable after 16-hr CI following 15-min WI in this experimental nonheartbeating donor model. HTK solution seems to provide reliable graft function in this setting and to be equivalent to UW.

Topics: Adenosine; Allopurinol; Amylases; Animals; Cold Temperature; Edema; Glutathione; Graft Survival; Hot Temperature; Hyperinsulinism; Hypoglycemia; Insulin; Lipase; Models, Animal; Organ Preservation; Organ Preservation Solutions; Pancreas; Pancreas Transplantation; Raffinose; Reperfusion Injury; Swine

Topics: Allopurinol; Bicarbonates; Blood Glucose; Diazoxide; Gluconeogenesis; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease Type I; Growth Disorders; Humans; Hypoglycemia; Liver; Liver Glycogen; Uric Acid

Severe hypoglycemia and increased deaths were observed among two strains of endotoxin-poisoned mice within 3 to 6 hr after tryptophan injection. Sensitivity to tryptophan could be demonstrated in Rockland Farms mice by 4 hr after endotoxin and in Carworth Farms (CF-1) mice by 10 hr after endotoxin. If allopurinol was given to CF-1 mice concurrently with endotoxin, severe hypoglycemia and increased deaths were observed when tryptophan was given only 4 hr after the bacterial poison. Cyproheptadine, an antiserotonin drug, decreased the number of deaths as well as the depletion of blood glucose in both strains of endotoxin-poisoned mice given a delayed injection of tryptophan. In most instances, liver glycogen was depleted by 8 to 10 hr after endotoxin. Correlation of liver glycogen levels with sensitivity to tryptophan was not as consistent as the correlation between blood glucose levels and hyperreactivity to the amino acid. The data show that severe hypoglycemia is a significant factor which must be considered in resolving the basis for increased deaths among endotoxin-poisoned mice given tryptophan.

Topics: Allopurinol; Animals; Blood Glucose; Carbohydrate Metabolism; Cyproheptadine; Drug Interactions; Endotoxins; Female; Hypoglycemia; Lethal Dose 50; Liver Glycogen; Mice; Mice, Inbred Strains; Salmonella typhimurium; Time Factors; Tryptophan