Spring 2013 The Congenital Hyperinsulinism Center hi HOPE n\ meet our TEAM Focus on Medically Managed Patients Endocrinology Of the total population of children who are diagnosed with congenital hyperinsulinism (HI), approximately half have diffuse disease, which means the insulin-spewing beta cells are distributed throughout their pancreas. A small percentage of the children who have diffuse HI and are unresponsive to diazoxide can be managed medically and avoid surgery to remove most of their pancreas. Diva D. De León-Crutchlow, M.D. Director, Congenital Hyperinsulinism Center Andrea Kelly, M.D. David Robert Langdon, M.D. Andrew Palladino, M.D. Charles A. Stanley, M.D., Founder, Congenital Hyperinsulinism Center Nursing Staff Linda Boyajian, M.S.N., C.R.N.P. Teresa Dansbury, B.S.N., R.N. Enyo Dzata, M.S.N., C.R.N.P. Amanda Lee, M.S.N., C.R.N.P. SURGERY Diffuse Disease Treated Without Surgery From the looks of Naomi* now, a bright kindergartner who knows her ABCs and is teaching herself to read, you’d never know she went for nine months before her congenital hyperinsulinism (HI) was properly treated. “We are so grateful that she never had any seizures or brain damage,” her mother, Esther*, says. “She never had any symptoms, other than low blood sugars.” Low as in really low, from Naomi’s second day of life. RADIOLOGY Esther had a normal pregnancy and delivery in her local Brooklyn, N.Y., hospital and thought all was well until a doctor rushed in the next morning and said Naomi had been moved to the Newborn Intensive Care Unit because of hypoglycemia. Doctors began to give her dextrose intravenously, thinking the lows would pass. They upped the amount, but still Naomi was hypoglycemic. It wasn’t until a week had passed that she was started on diazoxide, the frontline medication for HI. It seemed to help, at least a little. Diego Jaramillo, M.D., M.P.H. Chief, Department of Radiology, Radiologist-in-chief Lisa J. States, M.D. Hongming Zhuang, M.D., Ph.D. Naomi at 6 months After five weeks in the NICU, Naomi came home. Esther and her husband had been taught how to pump her full of dextrose and were given strict instructions: “Feed her every three hours, on the dot,” Esther says. “She grew a lot of facial hair, and she was fat, really fat, because we were always feeding her.” PATHOLOGY A stomach virus at 7 months landed Naomi back in the local hospital, where doctors placed a feeding tube through her nose to better keep the dextrose flowing. After Naomi spent two months in and out of the hospital, the local endocrinologist admitted he couldn’t help her and recommended Esther bring Naomi to CHOP. “They were at a loss what to do,” Esther says. “One night, her low sugars dropped to 18.” N. Scott Adzick, M.D., M.M.M. Chief of General, Thoracic and Fetal Surgery, Surgeon-in-chief PEDIATRIC ANESTHESIOLOGY Ari Weintraub, M.D. Pierre A. Russo, M.D. Chief, Anatomic Pathology Eduardo Ruchelli, M.D. NEONATOLOGY Jacquelyn Evans, M.D. Director, N/IICU Rebecca A. Simmons, M.D. DEVELOPMENT Mary Cooney Contact us at [email protected] Once under the care of Charles Stanley, M.D., in the Congenital Hyperinsulinism Center, Naomi was diagnosed with diffuse disease and started on a regimen of twicedaily shots of octreotide with continuous dextrose via a feeding tube overnight. Most children with the genetic mutation Naomi has, the common Ashkenazi Jewish ABCC8 HI mutation, require a 95 to 98 percent pancreatectomy. However, Naomi was stable and ready to go home in two weeks. The nasogastric tube was replaced with a gastrostomy tube a few months later, and the combined octreotide-dextrose continued on next page Continued from front Diffuse Disease Treated Without Surgery treatment has controlled her HI ever since. At CHOP, only a small percentage of patients with recessive mutations in ABCC8 have been able to be treated without surgery. “She’s totally normal, rambunctious, lively,” says Esther. “The only help she gets is from a health paraprofessional, who checks her sugar and gives her something to eat if it’s low.” And that’s only as a precaution. Naomi has been checking her own sugar since she was 3, smart girl that she is. *Names were changed at the family’s request. Gastrostomy Tube Tips and Reminders By Amanda Lee, M.S.N., C.R.N.P. For many children with HI, having a gastrostomy tube means having a lifeline. Whether the tube is used for occasional boluses of dextrose when a blood sugar is low or for continuous administration of dextrose water overnight, the easy access it provides is essential. But the gastrostomy tube (GT) is not without its challenges. From securing it early on when a baby with HI begins to roll over in his crib, to finding a backpack for carrying the pump around when the child is older, each developmental stage can bring a new challenge. Here are a few pointers and reminders for those with a GT: 1.Even if you live far away from CHOP, it is a good idea to be seen intermittently by a pediatric surgeon and his or her team. They can help with tube sizing, tube removal and tube replacement, if it ever comes out. Your pediatrician can recommend a local pediatric surgeon if you do not already have one. 2.Skin care is easy. The stoma (opening) site and surrounding area only need to be washed with mild soap and water. Anything more than this can cause skin breakdown. Some yellow-brown drainage at the site is normal. Please contact your surgical care provider to check out any leakage at the site. 3.Some granulation tissue may develop at the site. It is typically dark pink or red, and it is the body’s natural response to the tube. If your child has a lot of this tissue, there can be leakage and skin irritation. Please contact your surgical care team for treatment of painful granulation tissue. 4.Do you remember what to do if the GT comes out? No matter how long the GT has been in place, the opening can close very quickly. If you have a Foley catheter (and you should), place the end of it into the stoma about 1 to 2 inches and tape in place. Then call your child’s doctor right away. 5.Always remember that your child’s tube does not need to affect normal activities. Your child can bathe, play, swim and sleep; it just might require some creativity! Please contact us with any questions or concerns, or if you need help troubleshooting. We’re available at 215-590-7682 or [email protected]. Pilot Study Investigational Drug Shows Promise for Diffuse HI Patients Children’s Hospital, building on a pilot study in adolescents and adults, has found that an investigational drug, exendin-(9-39), could point to the first potential medical treatment for children with the severest type of congenital hyperinsulinism. These children currently face a near-total pancreatectomy. About half of HI patients, who have diffuse disease and are unresponsive to diazoxide, could potentially benefit. Under the leadership of Diva D. De León-Crutchlow, M.D., director of CHOP’s Congenital Hyperinsulinism Center, study results showed that exendin-(9-39) successfully increased fasting blood glucose in nine patients, aged 15 to 47 years old, who had hyperinsulinism caused by mutations in potassium channels. The study provides proof of concept that will allow for larger studies in the future, and hopefully FDA approval of the medication. The center is preparing an expanded clinical study for 2014. Exendin-(9-39) blocks the action of a hormone, glucagonlike peptide-1 (GLP-1), in beta cells. The GLP-1 receptor is currently the target of drugs that treat diabetes, using the opposite effect from that investigated in this HI study. None of the study subjects were being treated for HI at the time of the study, but all were at risk of hypoglycemia during periods of fasting. In all nine, the drug controlled blood glucose levels during fasting. Exendin-(9-39) also controlled insulin secretion in cell studies of beta cells taken from newborns with HI. Also, De León-Crutchlow and HI Center researcher Katherine Lord, M.D., are studying how many children with surgically treated hyperinsulinism develop diabetes and developmental or behavioral problems. From this study, researchers hope to better understand the long-term risks associated with hyperinsulinism and its treatments and provide better guidance to families. The center is enrolling subjects who had a pancreatectomy for HI between 1960 and 2008. Subjects will be asked to do an interview with researchers about their blood sugars and medical history and also to complete two developmental/behavioral screens. The interview can be done over the telephone, and the screens will be mailed to subjects. Some subjects can also undergo free diabetes screening and formal neurodevelopmental testing, if they are willing and meet certain criteria. Please call Lord at 267-425-2125 or email her at [email protected]. A Grandfather’s Love Will Help Many HI Patients There is no doubt that Oliver Fallon is one of the lucky ones — if you can call getting a rare disease like congenital hyperinsulinism (HI) lucky. Oliver didn’t have any signs of low blood sugar until he was weaned from breastfeeding at 6 months old. When he had a seizure at home, his parents rushed him to Mount Sinai Hospital in New York City, where the emergency room doctors tested his blood immediately and found the hypoglycemia. Physicians there were able to diagnose him with HI within a week. Oliver was put on diazoxide, and it worked. With the medication and some diet changes, his HI was well controlled. Oliver Fallon with his grandfather, Clifford Goldsmith To top off his good luck story, Oliver has outgrown the disease and is no longer on medication, putting him among the approximately 5 percent of medically managed HI patients able to halt medication. Oliver, now 9, is a typical kid; he plays baseball and the piano. about Dr. (Charles) Stanley and suggested we talk to him.” When Oliver came to CHOP in 2004 for protein and fasting tests, Goldsmith and his wife, Katherine, came along. But his grandfather, Clifford Goldsmith, knows there are other children whose experience with HI is much more difficult. To help them and future patients, Goldsmith has made generous donations to the Congenital Hyperinsulinism Center at The Children’s Hospital of Philadelphia to fund HI research. The first set of tests showed that Oliver could indeed eat protein without making his blood sugar plummet. That allowed him a more balanced diet. And a year ago, Oliver came back to CHOP for more tests that showed he didn’t need diazoxide anymore. In between, Goldsmith had met with Charles Stanley, M.D., who founded the HI Center, and Diva D. De León-Crutchlow, M.D., the center’s director. His favorable impression of the HI Center grew, and he signed on to support its research. The HI lab is now named Fallon-Goldsmith Hyperinsulinism Laboratory in honor of his gift. “I know it’s hard to find funding for rare diseases,” says Goldsmith, a trustee at Mount Sinai who has funded a center for multiple sclerosis there in memory of his daughter Corrine, who had MS. Why CHOP? Even though Oliver was doing well on the medication eight years ago, his doctors had put him on a lowprotein diet. Oliver’s mother and Goldsmith’s daughter, Alex Fallon, says her father was “Googling around and found out “I was so impressed by everything that went on at CHOP,” Goldsmith says. “They did so much to help Oliver.” “I was so impressed by everything that went on at CHOP,” Goldsmith says. “They did so much to help Oliver.” Every Monday, Oliver goes to his grandparents’ apartment in New York City for his weekly piano lesson. Afterward, he stays for dinner and listens to his grandfather talk about his childhood in Germany. Goldsmith left Germany when he was 16, went to college in England, came to the United States when he was 20 and, when World War II broke out, volunteered for service in the U.S. Army. He was captured by the Germans and spent five months as a prisoner of war in Germany. It’s compelling stuff for a 9-year-old with a penchant for history. But Oliver has fought his own battle and, remarkably, he’s won. And now his grandfather is arming CHOP’s HI Center to continue the fight to find better treatments and hopefully, one day, a cure for congenital hyperinsulinism. De León-Crutchlow Assumes Leadership of Center Charles Stanley, M.D., who has treated patients with congenital hyperinsulinism before the disease was even routinely called that, has moved into the director emeritus position at CHOP’s Congenital Hyperinsulinism Center, which he formally founded in 1998. Dr. Stanley, a world-renowned expert on disorders of insulin regulation in children, will continue to conduct research at the center. Charles Stanley, M.D. Diva D. De LeónCrutchlow, M.D. Diva D. De León-Crutchlow, M.D., who has been at CHOP since 1999, is now director of the center. Her research interests focus on the interaction between glucagonlike peptide-1 and the insulin-producing pancreatic beta cells in the pathogenesis of congenital hyperinsulinism and other hypoglycemic disorders. 11 NW Tower, Suite 30 34th Street and Civic Center Boulevard Philadelphia, PA 19104-4399 Address service requested. We’re proud to announce that the Parents magazine 10 Best Children’s Hospital survey ranked The Children’s Hospital of Philadelphia No. 1 overall nationwide. See the survey in the March 2013 issue as well as online at www.parents.com. The Division of Endocrinology at CHOP is ranked No. 1 among all pediatric hospitals in U.S.News & World Report’s Best Children’s Hospitals survey for 2012-13. CHOP also tied for the No. 1 ranking overall on U.S.News & World Report’s Honor Roll of Best Children’s Hospitals. (Parents does not rank Endocrinology.) Childhood is a gift and you can give it. For information about giving to The Children’s Hospital of Philadelphia, contact Mary Cooney 267-426-6468 [email protected]. ©2013 The Children’s Hospital of Philadelphia, All Rights Reserved. 7422/900/05-13 We’re No. 1 Twice!