Background: Hyperinsulinemic hypoglycemia (HH) is the most common cause of severe, persistent neonatal hypoglycemia. Treatment of diffuse forms that is unresponsive to diazoxide and octreotide is near total pancreatectomy.
Objective: To describe the clinical characterization of a newborn with congenital HH due to a diffuse pancreas lesion and unresponsive to diaxoside.
Case report: Preterm term male of 33 weeks born to non-consanguineous Chilean parents at normal delivery. Birth weight 3030 g (>90th ce), length 44.5 cm (50th ce) and HC 34 cm (>90th ce). Apgar scores was 8 at 1 min and 9 at 5 min. He was non-dysmorphic and systemic examination was unremarkable. At 5 h of life his blood glucose level it was 20 mg/dl, concomitant insulin was increased (36 uU/ml) and ketone bodies are negative. HH was suspect. He was treated with i.v. glucose infusion (up to 19 mg/kg per min and s.c. glucagon 5 μg/kg per h but remained hypoglycaemic, so glucagon was increase up to 8 μg/kg per h. The patient was started on diazoxide (with hydrochlorothiazide) at 10 mg/kg per day on day 3 and then increased to 20 mg/kg per day but continued requirement of high glucose load and glucagon to maintain normal glucose levels. Ten days of life the patient failed to respond to diazoxide and sc octreotide was started (5 μg/kg per day to 25 μg/kg per day) with a good response. Sequence analysis for the ABCC8 and KCNJ11 gene showed no mutation. 68Ga dotatate PET/CT shows a diffuse compromise of the pancreas. 30 days of life the patient present and acute cholecystitis, so suspension of octreotide was decided. Glucose load and glucagon must be recommence. So the patient failed to respond to maximal dose of diazoxide and have major side effect with octreotide. At 2 month age, before to decide surgery of near total pancreatectomy, we decide treatment with Sirolimus an Mtor pathway inhibitor at of 0.5 mg/m2 of body-surface area per day orally. The dose was gradually increased with the goal of reaching a serum trough level of 515 ng/ml. Over a period of 1 month the patient maintained stable blood glucose levels. Glucose infusion and glucagon were then gradually discontinued. The patient discharge at 3 month of age, with enteric feeding every 4 h, without hypoglycemia and sirolimus doses of 1 mg/m2 of body surface and plasmatic levels of 5 ng/ml.
Conclusion: We present a case of a newborn with congenital hyperinsulinism due to a diffuse compromise of the pancreas without response to maximal dose of Diaxoside. We decide to try with oral sirolimus. The patients had a good glycemic response to sirolimus. There were no adverse events during 10 month of follow-up.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology