Severe Hypoglycemic Seizures in a Child Receiving 6-Mercaptopurine

El-Bitar, Mohamad K.; Muwakkit, Samar; Dabbagh, Omar

doi:10.1097/mph.0b013e3182025507

Cited by 13 publications

(16 citation statements)

References 4 publications

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“…Symptomatic hypoglycemia due to 6-MP is one of its rare side effects, and only a few cases have been reported. El-Bitar et al [6] reported prolonged generalized tonic nocturnal seizures and severe hypoglycemia in a 4-year-old boy who was diagnosed with ALL and received 6-MP as maintenance therapy. The symptoms occurred after taking the evening dose of 6-MP after a 12-hour period of fasting.…”

Section: Discussionmentioning

confidence: 99%

“…In most of the literature, this condition was treated with a similar approach, and hypoglycemia was found to be improved [3,5,11]. For children aged under 6 years in particular, it is recommended to wake up and drink milk or juice after 8 to 9 hours of sleep [6,8]. If hypoglycemic symptoms are very severe, the dose of 6-MP may be reduced for a short period of time [7].…”

Section: Discussionmentioning

confidence: 99%

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Severe recurrent nocturnal hypoglycemia during chemotherapy with 6-mercaptopurine in a child with acute lymphoblastic leukemia

Cho

Moon

Lee

et al. 2018

Ann Pediatr Endocrinol Metab

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Various endocrine dysfunctions occur during chemotherapy, including hypoglycemia. However, reports of hypoglycemia associated with 6-mercaptopurine (6-MP) are rare. Herein, we report an 8-year-old boy with severe symptomatic hypoglycemia likely due to 6-MP during chemotherapy. He had been diagnosed with acute lymphoblastic leukemia 3 years previously and was in the maintenance chemotherapy period. Treatment included oral dexamethasone, methotrexate, and 6-MP, of which only 6-MP was administered daily. Hypoglycemic symptoms appeared mainly at dawn, and his serum glucose dropped to a minimum of 37 mg/dL. Laboratory findings showed nothing specific other than increased serum cortisol, free fatty acids, ketone, alanine aminotransferase, and aspartate aminotransferase. Under the hypothesis of hypoglycemia due to chemotherapy drugs, we changed the time of 6-MP from evening to morning and recommended him to ingest carbohydrate-rich foods before bedtime. Hypoglycemia improved dramatically, and there was no further episode during the remaining maintenance chemotherapy period. To the best of our knowledge, this is the first report of this type of hypoglycemia occurring in an Asian child including Korean.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Severe recurrent nocturnal hypoglycemia during chemotherapy with 6-mercaptopurine in a child with acute lymphoblastic leukemia

Cho

Moon

Lee

et al. 2018

Ann Pediatr Endocrinol Metab

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“…It is interesting that 6-MP, when used to treat leukemia in children, has resulted in unexplained symptomatic hypoglycemia (7,12,44). In this study, we found that 6-MP was able to augment glucose transport and GLUT4 translocation in basal muscle cells even in the absence of insulin.…”

Section: Discussionmentioning

confidence: 89%

6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in part via a mechanism dependent upon orphan nuclear receptor NR4A3

Liu

Zhu

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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The purine anti-metabolite 6-mercaptopurine (6-MP) is widely used for the treatment of leukemia and inflammatory diseases. The cellular effects of 6-MP on metabolism remain unknown; however, 6-MP was recently found to activate the orphan nuclear receptor NR4A3 in skeletal muscle cell lines. We have reported previously that NR4A3 (also known as NOR-1, MINOR) is a positive regulator of insulin sensitivity in adipocytes. To further explore the role of NR4A3 activation in insulin action, we explored whether 6-MP activation of NR4A3 could modulate glucose transport system activity in L6 skeletal muscle cells. We found that 6-MP increased both NR4A3 expression and NR4A3 transcriptional activity and enhanced glucose transport activity via increasing GLUT4 translocation in both basal and insulin-stimulated L6 cells in an NR4A3-dependent manner. Furthermore, 6-MP increased levels of phospho-AS160, although this effect was not modulated by NR4A3 overexpression or knockdown. These primary findings provide a novel proof of principle that 6-MP, a small molecule NR4A3 agonist, can augment glucose uptake in insulin target cells, although this occurs via both NR4A3-dependent and -independent actions; the latter is related to an increase in phospho-AS160. These results establish a novel target for development of new treatments for insulin resistance.

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“…Thus far, these methods have only been reported in patients experiencing hypoglycemia. Two cases demonstrated complete reversal of symptoms with changes in timing of 6-MP administration plus a carbohydrate-enriched diet, whereas these methods failed to resolve hypoglycemic episodes in two other reports (25)(26)(27)(28). A fifth case required 6-MP dose reduction in addition to morning administration to achieve the desired response (29).…”

Section: Clinical Use Of Allopurinol To Mitigate 6-mp Toxicity Duringmentioning

confidence: 96%

Use of Allopurinol to Mitigate 6-Mercaptopurine Associated Gastrointestinal Toxicity in Acute Lymphoblastic Leukemia

2020

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An essential component of acute lymphoblastic leukemia (ALL) therapy is the prolonged maintenance phase with daily 6-mercaptopurine (6-MP) as the cornerstone. While 6-MP is generally well-tolerated, some patients suffer from significant side effects such as gastrointestinal (GI) toxicity, including hepatitis, hypoglycemia, nausea, and pancreatitis, which can substantially limit the tolerated dose of 6-MP. These toxicities are thought to result from skewed metabolism of 6-MP leading to an accumulation of the 6-methylmercaptopurine (6-MMP) metabolite. Here, we describe current knowledge behind the use of allopurinol to modify 6-MP metabolism and improve tolerance to therapy. This method has been successfully used in adults with inflammatory bowel disease refractory to purine therapy and has been modified for use in children with GI toxicities related to 6-MP in maintenance therapy for ALL. Use of allopurinol for 6-MP related toxicities should be reserved for patients in which an alternative cause of signs or symptoms has been excluded and for whom non-pharmacologic measures have failed. When allopurinol is used, simultaneous dose reduction of 6-MP is required to avoid severe myelosuppression and related side effects, though overall combination therapy appears to be well-tolerated and effective when instituted appropriately.

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Severe Hypoglycemic Seizures in a Child Receiving 6-Mercaptopurine

Cited by 13 publications

References 4 publications

Severe recurrent nocturnal hypoglycemia during chemotherapy with 6-mercaptopurine in a child with acute lymphoblastic leukemia

Severe recurrent nocturnal hypoglycemia during chemotherapy with 6-mercaptopurine in a child with acute lymphoblastic leukemia

6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in part via a mechanism dependent upon orphan nuclear receptor NR4A3

Use of Allopurinol to Mitigate 6-Mercaptopurine Associated Gastrointestinal Toxicity in Acute Lymphoblastic Leukemia

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