IMPE Abstracts

Background: Persistent hypoglycemia in pediatric patients is the clinical manifestation of different hormonal and metabolic disorders and expose them to a high risk of brain damage. Appropriate management should include staggered strategy to achieve the underlying etiology.

Aim: To describe an infant with recurrent hypoglycemia due to Stage 4 Neuroblastoma (4SNB) behaving as an “IGF2-OMA”.

Case report: A 2-month boy admitted with a huge high consistency abdominal mass and multiple bluish cutaneous nodules. Male genitalia, Tanner stage I, testicular volume of 2 ml. 4SNB was confirmed. While being critically ill, recurrent hypoglycemic episodes occurred (glycemia levels 13 to 36 mg/dL). Critical sample showed non-detectable insulin and C peptide, bOHbutirate 0.05 mmol/L, NEFA 0.49 mmol/L, GH 0.27 ng/mL, IGF1 <15 ng/mL, IGFBP3 0.9 µg/mL and cortisol 15.1 µg/dL. Non clear cause of persistent hypoglycemia in the presence of large abdominal tumor, raised the question of tumor´s overproduction of IGF2 and Big-IGF2.

Methods: IGF2, Big-IGF2 and IGFBP-2 measurement were evaluated by western immunoblotting from patient´s serum samples at three stages of the disease, two healthy infants and two growth hormone deficient (GHD) patients age-matched controls.

Results: Strong high molecular weight IGF2 bands (Big-IGF2, MW above 17Kda) were present only in samples from index case during clinical recurrent hypoglycemia and absent in controls, while bands corresponding to IGF2 (MW below 17KDa) were observed in healthy controls and absent in GHD patients. IGFBP2 bands were more intense in the index patient than in GHD and healthy controls. Temporal measurement of Big-IGF2 bands showed progressive reduction, in correlation to clinical improvement and normalization of blood glucose. Hypoglycemia was attributed to the diagnosis of IGF2-OMA and only support treatment was instituted to control glycemia.

Conclusions: IGF2 overproduction is a rare complication of many solid tumors and should be considered on the differential diagnosis if hypoglycemia occurs. Excessive IGF2 and Big-IGF2 interferes in the normal GH-IGFs-Insulin pathways by binding insulin receptors and IGF1 receptors and overstimulates the post receptor pathways. The biochemical pattern of hyperinsulinemic hypoglycemia in the absence of elevated serum insulin and C peptide associated to low GH, IGF-1 and IGFBP3 mimicking GHD, suggests IGF2/Big-IGF2 overproduction as the stimulating factor of glucose consumption as well as inhibition of the GH/IGF axis. IGF2-OMAs should be consider as a potential cause of hypoglycemia in infants and children with solid tumors without clear evidence of other common causes.