ESPE Abstracts (2015) 84 P-2-295

Sirolimus Therapy in Infants with Congenital Hyperinsulinism after Near Total Pancreatectomy

keun Hee Choi & Hye Rim Chung

Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

Background: Congenital hyperinsulinism is the most common cause of persistent hypoglycaemia in neonates and children. It is important to minimize recurrence of episodes of hypoglycaemia. In some cases, Hypoglycemia was not controlled even after near total pancreatectomy.

Objective and hypotheses: To study the glycemic response of sirolimus in patients with hyperinsulinemic hypoglycaemia that was not responsive to octreotide and calcium channel blocker after near total pancreatectomy.

Method: A 35+4 weeks appropriate for gestational age neonate was presented with severe hypoglycemia on day 1 of life. Because of severe hyperinsulinemic hypoglycaemia that was unresponsive to maximal dose of diazoxide (20 mg/kg per day), octreotide (35 μg/kg per day) and amlodipine (1.5 mg per day), the patient was underwent near total pancreatectomy at 3 months of age. In genetic study, single heterozygous mutation in KCNJ11 (C406C>7, p.Arg136Cys) was reported. After pancreatectomy, hypoglycaemia which was unresponsive to octreotide and amlodipine was recurred. Sirolimus was started at an initial dose of 0.5 mg per square meter of body-surface area (0.2 mg) per day in one dose to the patient. The dose was increased slowly to achieve serum trough level of 5–15 ng per ml. The serum trough level of sirolimus was measured 5–15 days interval. Regular monitoring of complete blood count, serum lipid levels, renal function and liver function test was performed.

Results: A good glycemic control was achieved. Amlodipine and i.v. glucose infusion were discontinued and the dose of octreotide was gradually decreased. The patient was discharged with 0.6 mg per day of sirolimus and 12 μg/kg per day of octreotide 12 day after sirolimus use. After 3 months, the dose of sirolimus was increased up to 1.5 mg per day and sirolimus trough level was 6.2 ng/ml. Elevation of liver aminotransferase levels was observed (AST 50 IU/l). Except that, no other side effect of sirolimus was found. Blood glucose was maintained about 60–100 mg/dl.

Conclusion: Severe hyperinsulinemic hypoglycemia due to single heterozygous mutation of KCNJ11 was responded to therapy with sirolimus with mild side effect.

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