Diva De Leon-Crutchlow, MD, MSCE: Hyperinsulinism is the most common cause of persistent hypoglycemia in neonates, infants, and children. This is a condition that affects the pancreatic beta cell, where genetic defects impact the pathway that normally regulates the secretion of insulin. So the pancreas is a very important organ that has two functions.

One function is to secrete enzymes that are important for digestion. The other function is to secrete hormones that regulate blood sugar levels. One of those hormones is insulin, and when you do not produce enough insulin, you develop diabetes and your blood sugar levels are high. Hyperinsulinism is the opposite to diabetes.

In this case, the pancreas secretes too much insulin and blood sugar levels are low.

Hyperinsulinism carries a very high risk of brain damage for the lack of fuel for brain functioning. Glucose is the main source of energy for the brain, and when glucose levels are low, the brain is deprived of that energy. So the goal is to identify them very early and treat the hypoglycemia with the goal of improved long-term outcomes.

Hyperinsulinism is a very rare condition. In this country, we estimate that about 1 in every 28,000 babies have hyperinsulinism. And because of this, most children hospital only see one or two cases a year, while at CHOP, we see an enormous number. 

N. Scott Adzick, MD, MMM: Children's Hospital of Philadelphia and the Congenital Hyperinsulinism Center is the epicenter for the treatment of babies with congenital hyperinsulinism.

Diva De Leon-Crutchlow, MD, MSCE: We have a very good understanding now of how to manage these babies. So since 1998, when the center was established, we have seen more than 1,900 cases.

The most common time of presentation is immediately after the new baby's born. Very commonly, newborn babies with low blood sugars may not have clear manifestations until they have a severe episode like a seizure. So it's very important that subtle symptoms are recognized by the parents or by the nurses that are taking care of that baby, and those may include abnormal eye movements, irritability, difficulty feeding, and as I said before, a seizure.

But you really want to identify them before they have a seizure. Diazoxide is the only medication approved in this country for the treatment of hyperinsulinism, and it works in the pancreatic beta cells, suppressing insulin secretion.

So for those children that respond to diazoxide, treatment with the medication makes an incredible difference. So the comprehensive evaluation of babies with hyperinsulinism requires really step-by-step testing to determine the best treatment options. So once we have determined whether there's response to diazoxide, the following step may be genetic testing.

Genetic testing is a very important part of the evaluation of children with hyperinsulinism. In the last 20 to 25 years, we have developed a very good understanding of the genetic causes of hyperinsulinism. Actually, many of those discoveries were done here at CHOP. So as part of the evaluation, a blood sample is taken to do this genetic testing.

And what the genetic testing includes is looking at the genes that are known to cause hyperinsulinism to see if there's a defect in one of them.

When we suspect focal hyperinsulinism based in the lack of response to treatment with diazoxide and the genetic testing results, the next step is to do specialized imaging using a 18F-DOPA-PET CT, a test that is available in very few centers in the world. So the test is done, and you can see where in the pancreas the lesion is.

The cure rate of focal hyperinsulinism at our center is 97%. So we can basically cure almost every baby that comes to our center with focal hyperinsulinism, and that means that the hyperinsulinism is gone. They don't need any further treatments. They grow and develop normally after that lesion is removed from their pancreas.

N. Scott Adzick, MD, MMM: The question is, does experience matter in the surgical treatment of congenital hyperinsulinism? And unequivocally, yes. I've done close to 700 pancreatectomies in babies with the focal form and the diffuse form of the disease. That's more than any center in the world by far. The surgical approach at the beginning is the same for a baby with focal disease as for diffuse disease.

A sideways wound is made above the level of the belly button, and the pancreas is exposed. The pancreas has a head, a neck, a body, and a tail. I examine the pancreas using magnifying loops that magnify things by a factor of four, and often there are little visual hints as to where a focal lesion might be.

I also palpate the pancreas because focal lesions tend to be firmer than surrounding normal pancreas. The preoperative PET scan is a huge leap in finding focal lesions and serves for me as a GPS for identification of a focal lesion. A focal lesion can be as small as two to three millimeters, and sometimes can be very tricky to find, even with the preoperative information from the PET scan.

A focal lesion in the tail or the body or the neck can often be excised locally as long as it does not involve the main pancreatic duct. The pancreatic duct is a pipeline through which pancreatic secretions and enzymes run, and I don't wanna cause an injury to the pancreatic duct. In those cases, I remove the end of the pancreas, along with the focal lesion, whereas focal lesions in the head and neck of the pancreas are more complex because there's all this important traffic that goes through or around the pancreatic head and neck.

So it's a very fine, very delicate operation. So if you take a focal lesion of the head out and have to take out the pancreatic duct in that portion, then we've learned that it is important to resect the pancreatic head but save the body and tail. By bringing up a loop of bowel, it's called a Roux-en-Y loop, and connect the end of the bowel loop to the pancreatic body and tail so that those pancreatic secretions from those two structures can drain into the intestine where they belong, and so that we preserve the normal islet cells in the pancreatic body and tail.

If there are no abnormal findings by visualization and palpations, I do three biopsies, one from the head, one from the body, and one from the tail of the pancreas. When there's diffuse disease, all of the insulin-producing islet cells in the pancreas are abnormal, so there will be multiple biopsies taken just to be sure to confirm the diagnosis of diffuse disease.

The interaction between the surgeon and the pathologist is crucial. If there are abnormal diffuse disease findings on each of the three biopsies, then a near total pancreatectomy is done, saving all but a tiny nubbin of the pancreas between the duodenum and the common bile duct. This hopefully will help in the management of the disease in terms of prevention of brain-threatening hypoglycemia.

It's a wonderful feeling to leave the operating room having done something that will have a huge impact on a child's life and on that family. This was about a 5% pancreatectomy. That's wonderful.

Diva De Leon-Crutchlow, MD, MSCE: A lot of advances had happened in the last 30 years in hyperinsulinism, and we expect that further advances are continuing to be made by our research team and by teams that are doing research in this condition all about the world. What sets our team apart is really the expertise, the experience, the multidisciplinary team.

So it's not only the endocrinologist, but it's the gastroenterologist, the genetic specialist, the surgeon, the radiologist, the pathologist. We all come together around the care of every single patient that is evaluated here at CHOP. We're fortunate to be able to follow these babies throughout their life.

We meet them where they're newborn babies, and they come back to us throughout their school years, and we see them graduate from college. We see them playing baseball, football, and really leading into adulthood with the care that they have received here.