New drug treatment saves patients with rare condition from losing pancreas

A new drug treatment has saved four patients at Great Ormond Street Hospital (GOSH) from having their pancreas removed. 

The patients, who all have a severe condition which produces excess insulin in the body, are doing well a year after starting the treatment, reports a study in the New England Journal of Medicine. 

Hyperinsulinemic hypoglycemia (HH) is a condition where babies suffer with very low blood sugar levels due to an excess release of insulin from the pancreas. The severest forms of HH can lead to brain damage and other problems if not properly managed. GOSH is one of the two centres in the UK which care for children with HH.

Drugs such as diazoxide and octreotide are normally used to stabilise blood sugar levels, but the standard medication does not work for the severest forms of HH. In the worst case, surgeons must remove nearly the whole pancreas to eliminate the source of insulin. However, the surgery is not a cure; as some patients can continue to experience symptoms of HH and most patients go on to develop diabetes mellitus in their adolescence.

In the study led by GOSH, researchers pinpointed the molecular pathway most likely to be responsible for the overproduction of insulin. They then searched for an existing drug which might be able to block it, and identified the drug sirolimus which has been used to treat renal transplant patients. Four GOSH patients who had not responded to diazoxide and octreotide and whose remaining option was to have their pancreas removed were offered sirolimus as an alternative treatment. All four patients responded well to sirolimus treatment and were discharged home safely without the need to remove their pancreas.

Dr Senthil Senniappan, first author and Clinical Research Fellow at GOSH, said: “One year on, all the patients are doing well with stable blood glucose levels and no significant side effects. All four patients will continue to receive sirolimus but will be monitored closely for possible side effects which include the risk of infection, and effects on the kidney and liver functions”.

Dr Khalid Hussain, lead author and Consultant in Endocrinology at GOSH, said: “Identifying the key pathways involved in this disease has helped us to find the most suitable treatment for these patients. We hope that in the long-term, the treatment will lessen the severity of the condition, enabling patients to be moved onto more standard drugs such as diazoxide. This new discovery could change the way patients with hyperinsulinemic hypoglycemia are managed in the future.”

David, 1, from Bromley was first admitted to Great Ormond Street Hospital (GOSH) ten days after he was born.

David was transferred to GOSH after his local hospital discovered his blood sugar levels were low but did not respond to the drugs normally given to raise them.

GOSH consultants established that David had a condition known as hyperinsulinemic hypoglycaemia, where too much insulin is produced in the body, reducing blood sugar to dangerously low levels.

Doctors tried a variety of known drug treatments for the next two months, but were unable to stabilise his blood sugar. The last option was for David to have his pancreas taken out surgically, to remove the source of the excess insulin.

But there was one alternative – to try a new drug identified by the hospital’s endocrinology team, that would hopefully target the molecular pathways responsible for the excess insulin.

“Once David was given the drug, it was amazing,” says mum Kristina. “Within a few weeks he was much better and we were able to bring him home.”

Kristina adds: “David has now celebrated his first birthday, and we are very happy that the treatment is going well.”