Preoperative Evaluation of Infants with Focal or Diffuse Congenital Hyperinsulinism by Intravenous Acute Insulin Response Tests and Selective Pancreatic Arterial Calcium Stimulation

• Published in: The journal of clinical endocrinology and metabolism Vol. 89; no. 1; pp. 288 - 296
• Main Authors: Stanley, Charles A., Thornton, Paul S., Ganguly, Arupa, MacMullen, Courtney, Underwood, Patricia, Bhatia, Pooja, Steinkrauss, Linda, Wanner, Laura, Kaye, Robin, Ruchelli, Eduardo, Suchi, Mariko, Adzick, N. Scott
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-01-2004; Copyright by The Endocrine Society
• Subjects: Arteries; ATP-Binding Cassette Transporters; Biological and medical sciences; Calcium - administration & dosage; Congenital Hyperinsulinism - diagnosis; Congenital Hyperinsulinism - genetics; Congenital Hyperinsulinism - pathology; Congenital Hyperinsulinism - surgery; DNA Mutational Analysis; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Glucose - administration & dosage; Humans; Infant; Infant, Newborn; Insulin - blood; Male; Medical sciences; Mutation; Pancreas - blood supply; Pancreas - pathology; Potassium Channels - genetics; Potassium Channels, Inwardly Rectifying - genetics; Preoperative Care; Receptors, Drug; Sulfonylurea Receptors; Tolbutamide - administration & dosage; Vertebrates: endocrinology; Human; Diffuse; Intravenous administration; Calcium; Congenital; Insulin test; Acute; Infant; Stimulation; Inorganic element; Artery; Blood vessel; Circulatory system; Preoperative; Pancreas; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-030965

Infants with congenital hyperinsulinism often require pancreatectomy. Recessive mutations of the ATP-dependent plasma membrane potassium channel (KATP) genes, SUR1 and Kir6.2, cause diffuse hyperinsulinism. KATP channel mutations can also cause focal disease through loss of heterozygosity for maternal 11p, resulting in expression of a paternal mutation. This study evaluated whether focal vs. diffuse hyperinsulinism could be diagnosed by acute insulin response (AIR) tests and whether arterial calcium stimulation/venous sampling (ASVS) could localize focal lesions. Fifty infants with diazoxide-unresponsive hyperinsulinism were studied. Focal lesions occurred in 70% of the cases. Positive AIR calcium occurred in 17 of 30 focal and 10 of 13 diffuse cases (P < 0.04). Positive AIR tolbutamide occurred in 27 of 30 focal vs. seven of 13 diffuse cases (P < 0.02); KATP channel mutations were identified in four of the latter. ASVS localized the lesion in 24 of 33 focal cases (73%) but correctly diagnosed diffuse disease in only four of 13 cases. These results indicate that preoperative AIR tests do not distinguish focal vs. diffuse disease because some KATP channel mutations retain responsiveness to tolbutamide. The ASVS test can be used to localize focal lesions in infants. The combination of ASVS, careful intraoperative histologic analysis, and surgical expertise succeeded in correcting hypoglycemia in 86% of the infants with focal hyperinsulinism.