Philadelphia, Pa. -- A diagnostic test performed in newborns allows physicians to identify a rare, severe imbalance of insulin levels -- a disease that can be cured with organ-sparing surgery. The diagnostic test was developed by physicians at The Children's Hospital of Philadelphia, who reported their findings on June 21 at an international conference of the Endocrine Society in Toronto, Canada.
When insulin levels rage out of control in newborns with a condition called congenital hyperinsulinism (HI), irreversible brain damage may result. Medication can treat some forms of congenital HI, but other forms require surgery on the pancreas, the organ that produces insulin. The Children's Hospital team presented results of an acute insulin response test that allows physicians to accurately identify the subtype of congenital HI before surgery.
Accurate diagnosis is important because one type of HI is diffuse, occurring throughout the pancreas and requiring that 95 percent of the organ be removed, a procedure called near-total pancreatectomy. Focal HI, on the other hand, affects only one localized part of the pancreas and can be cured by surgically removing that portion. The different surgeries have different outcomes: "Children who must receive a near-total pancreatectomy are at risk for diabetes, while those undergoing partial pancreatectomy are cured of HI and not vulnerable to diabetes," said Charles A. Stanley, M.D., Director of the Hyperinsulinism Program at Children's Hospital and senior author of the study.
Clinical symptoms are indistinguishable between diffuse and focal HI, and microscopic cellular differences are not visible by standard imaging techniques or during a surgeon's visual examination of the baby's pancreas, which is about the size of an adult's finger. "Acute insulin response testing allows us to accurately differentiate between diffuse and local lesions, before surgery is performed," said Dr. Stanley. In January, after the acute insulin response test indicated an 11-week-old infant had focal HI, pediatric surgeons at Children's Hospital performed a partial pancreatectomy, removing the lesion. The child remains free of disease.
The excessive insulin levels found in HI cause hypoglycemia, a abnormally low level of blood sugar. Congenital HI is a rare disease, with its most severe form affecting an estimated 200 to 500 babies per year in the U.S. Recent genetic discoveries have shown that congenital HI can be broken down into six types, with the distinctions having important implications for a child's outcome and treatments, such as whether the disease is likely to respond to medicine or surgery.
In 1998, Dr. Stanley identified the gene defect in a form of HI associated with hyperammonemia, a high level of blood ammonia. He also collaborated in multicenter studies that classified the other subtypes of HI, distinguished by gene mutations affecting enzymes and potassium channels that govern insulin secretion. The particular gene defect in the focal HI described in the current study involves mutations that affect the potassium channel in beta cells, the cells in the pancreas that secrete insulin.
The acute insulin response test used at Children's Hospital requires infusing calcium and a diagnostic chemical called tolbutamide into the blood, then measuring the resulting insulin levels. If the measurements suggest focal disease, a second stage is performed. This involves infusing calcium into the arteries of the pancreas to determine the location of the abnormal cells. Pediatric surgeons then remove only the defective portion of the tiny organ.
Children's Hospital is currently the only medical center in the United States that conducts the acute insulin response test for congenital HI. "Providing full services for this condition requires sophisticated, multidisciplinary capabilities: in endocrinology, pediatric surgery, pathology and interventional radiology," said Paul Thornton, M.D., the clinical director of the Hyperinsulinism Program at Children's Hospital who collaborated with Dr. Stanley on the recent study. Further work by the hyperinsulinism team will focus on devising more effective treatments for the diffuse form of HI, which currently requires near-total pancreatectomy.
The Children's Hospital of Philadelphia, the nation's first children's hospital, is a leader in patient care, education and research. This 373-bed multispecialty hospital provides comprehensive pediatric services, including home care, to children from before birth through age 19. The hospital is second in the United States among all children's hospitals in total research funding from the National Institutes of Health.