Tramadol Induced Hypoglycemia Masquerading as a Seizure Disorder

Background: Common causes of hypoglycemia include hypoglycemic agents including exogenous insulin and insulin secretagogues, increased endogenous insulin, decline in circulating cortisol, human growth hormone and enzymes required for glucose production as well as hepatic and renal dysfunction. Case presentation: Patient presented to emergency room with re-current seizures treated with Levetricatem and Topiramate for 10 years with increased frequency of 2-3/week during last 6 months. During ER visits to different hospitals for these episodes, plasma glucose, 1.5-1.8 mM/L and undetectable levels of insulin, C peptide, proinsulin, Insulin antibodies eliminated hyperinsulinemia due to insulinoma, insulin secretagogues as well as exogenous insulin as a cause of hypoglycemia. Normal HGH, ACTH and cortisol responses at onset of  hypoglycemia excluded hypopituitarism with HGH and/or ACTH deficiency and primary adrenal insufficiency. Large tumor secreting IGF2 was eliminated by CT scans of chest and abdomen. Hepatic and renal disease as a cause of hypoglycemia were excluded as well by documentation of normal laboratory tests. Tramadol use in high daily dose confirmed by elevated urine levels and total remission of hypoglycemia and seizures following withdrawal of tramadol resulted in documenting this unique presentation of tramadol induced hypoglycemia. We believe lack of suppression of IGF2 in presence of hypoglycemia may indicate role of Tramadol in stimulating production or decreasing metabolism or clearance of IGF2 responsible for onset and perpetuation of hypoglycemia. Conclusion: A unique presentation of Tramadol induced hypoglycemia masquerading as a seizure disorder probably caused by IGF2 dysregulation.