First report on the use of pasireotide in a case of severe congenital hyperinsulinism due to a homozygous ABCC8 mutation.

Abstract

ABCC8 and KCJN11 mutations cause the most severe diazoxide-resistant forms of congenital hyperinsulinism (CHI). Somatostatin analogues are considered as second-line treatment in diazoxide-unresponsive cases. Current treatment protocols include the first-generation somatostatin analogue octreotide while pasireotide, a second-generation somatostatin analogue, may be more effective in reducing insulin secretion. Herein we report the first off-label use of pasireotide in a boy with severe therapy resistant form of CHI due to a homozygous ABCC8 mutation. After partial pancreatectomy, hyperinsulinism persisted and in an attempt to prevent further surgery, off-label treatment with pasireotide was started. Short-acting pasireotide treatment caused high blood glucose levels shortly after the injections. Long-acting pasireotide treatment resulted in more stable glycemic control. No side effects (e.g. central adrenal insufficiency) were noticed during a two-month treatment period. Because of recurrent hypoglycemia despite a rather high carbohydrate intake the boy finally underwent a near-total pancreatectomy at the age of 11 months. In conclusion, pasireotide treatment slightly improved glycemic control without side effects in a boy with severe CHI. However, the effect of pasireotide was not sufficient to prevent near-total pancreatectomy in this case of severe CHI.