Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism

Objectives: To identify infants with hyperinsulinism caused by defects of t he beta-cell adenosine triphosphate-dependent potassium channel complex and to distinguish focal and diffuse forms of hyperinsulinism caused by these mutations. Study design: The acute insulin response to intravenous calcium stimulation (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinis m caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patien ts with focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year- old with insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective glutamate dehydrogenase (6 months to 28 years), 4 SUR1(-/-) he terozygotes with no symptoms, and 9 normal adults. Three infants with conge nital focal disease, 1 with diffuse hyperinsulinism, and the child with ins ulinoma underwent selective pancreatic intra-arterial calcium stimulation w ith hepatic venous sampling. Results: Children with diffuse SUR1(-/-) disease and infants with congenita l focal hyperinsulinism responded to CaAIR, whereas the normal control grou p, patients with hyperinsulinism/hyperammonemia syndrome, and SUR1(+/-) did not. Selective arterial calcium stimulation of the pancreas with hepatic v enous sampling revealed selective, significant step-ups in insulin secretio n that correlated anatomically with the location of solitary lesions confir med surgically in 2 of 3 infants with congenital focal disease and in the c hild with insulinoma. Selective arterial calcium stimulation of the pancrea s with hepatic venous sampling demonstrated markedly elevated baseline insu lin levels throughout the pancreas of the infant with diffuse hyperinsulini sm. Conclusions: The intravenous CaAIR is a safe and simple test for identifyin g infants with diffuse SUR1(-/-) hyperinsulinism or with focal congenital h yperinsulinism. Preoperative selective arterial calcium stimulation of the pancreas with hepatic venous sampling can localize focal lesions causing hy perinsulinism in children. The combination of these calcium stimulation tes ts may help distinguish focal lesions suitable for cure by local surgical r esection.