Endocrine Abstracts

Introduction: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycmia in neonatles and children. CHI causes persistent hypoglycemia due to inappropriate over-secretion of insulin. Promt diagnosis and immediate management is important to avoid long-term neurological damage. Medical therapy includes the use of the somatostatin analog octreotide as a second line-treatement in diazoxide-unresponsive cases. Here we report a case of a patient with CHI successfully treated with pasireotide, a somatostatin analog with high affinity for somatostatin receptor 5.

Case description: The patient presented at the age of 8 years with recurrent episodes of nonfasting hypoglycemia with neuroglycopenic symptoms. A diagnosis of autonomous insulin secretion was biochemically confirmed by identifying an elevated insulin level of 22,9 µ UI/ml > 3 µ UI/ml and C-peptide was elevated (3,43 ng/ml > 0,6 ng/ml) measured during hypoglycemia (glucose 2.03 mmol/l). Glucose infusion rate to maintain euglycemia was 7 (mg/kg/min). Abdominal ultrasound, computed tomography and magnetic resonance imaging (MRI) did not identify any pancreatic abnormalities. Endoscopic ultrasound and octreotide receptor scintigraphy revealed no pathological findings. The patient was initially treated with frequent feeding with carbohydrate-enriched formula and diazoxide 10 mg/kg/j. At the age of 12 years treatment with sc injections of octreotide was added because of recurrent hypoglycemia. At the age of 12 years 6 months and after parental consent, we started therapy with the long-acting somatostatin analog pasireotide at the dose of 40 mg every 28 days. Potential side effects of pasireotide (elevated liver enzymes, hypothyroidism, and adrenal insufficiency) were monitored and did not occur. With this therapy, the patient was normoglycemic with a good growth rate, normal weight gain, and excellent neurodevelopment.

Discussion: Pasireotide is a second-generation somatostatin analogue with a strong affinity for four of the five SSTRs especially SSTR5, followed by SSTR2, SSTR3, and SSTR1 receptors. Pasireotide was first introduced for treating Cushing disease and acromegaly and is known to cause hyperglycemia as a side effect due to inhibition of insulin secretion. It has been proposed as a new treatment for CHI. Pasireotide has a much higher affinity for SSTR5 than the first-generation somatostatin analogues) and might be more effective in controlling hyperinsulinism.