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A 4-month-old with congenital hyperinsulinism responded well to off-label treatment with a breast cancer drug, researchers reported.

A newborn presented with severe congenital hyperinsulinism due to homozygous deletion of the ABCC8 gene but failed to respond to any convention medical therapies, Khalid Hussain, MBChB, MD, MSc, of Sidra Medicine in Doha and Weill Cornell Medicine-Qatar, and colleagues detailed in a correspondence.

The condition causes severe hypoglycemia in newborns and often requires pancreatectomy, which may lead to diabetes and pancreatic exocrine insufficiency.

After the infant was referred to their center, Hussain's team started the infant on alpelisib (Piqray) -- an α-selective phosphatidylinositol 3-kinase (PI3K) inhibitor that was approved for the treatment of PIK3CA-mutated breast cancer and overgrowth syndromes.

During treatment, there was a substantial reduction in the percentage of time below the target range (under 63 mg/dL). By week 13, continuous glucose monitoring showed the patient only spent 2% of time below target range.

"One of the major side effects of this medication is high blood glucose levels, so [we] leveraged this observation to treat severe hypoglycemia," Hussain told 口袋女优. "Our observations in this case show that alpelisib therapy might help to reduce the severity of hypoglycemia in patients who have the most severe forms of congenital hyperinsulinism and thus avoid the need for a radical procedure, [like a] total pancreatectomy where patients will develop lifelong diabetes mellitus."

"If doctors are looking after patients with severe forms of congenital hyperinsulinism, then before proceeding to undertake a total pancreatectomy, I would recommend they give a trial of alpelisib therapy," he advised other clinicians.

His group referenced where a patient with intractable non-islet-cell tumor hypoglycemia was treated with alpelisib, which improved glucose levels.

In the current case, the patient previously failed conventional therapies diazoxide, nifedipine, hydrocortisone, and octreotide. To maintain "acceptable" blood glucose levels, the referring hospital started the baby on a combination of intravenous dextrose therapy, continuous gastrostomy-tube feeding, and injections of long-acting release octreotide (15 mg once every 4 weeks).

Hussain's team started the 4-month-old on a minimum dose of alpelisib at 12.5 mg once daily, which was increased to 25 mg twice day between weeks 2 through 8. From weeks 9 through 13, the alpelisib dose was bumped to 30 mg twice daily.

Then, 6 weeks after starting treatment, intravenous dextrose therapy was discontinued and continuous gastrostomy tube feeding was changed to bolus feeding every 3 hours. Injections of long-acting release octreotide once every 4 weeks were still given.

The patient experienced few adverse events, which included vomiting, retching, and a mild elevation in the serum insulin level. These effects were dose-dependent, occurring at the 30 mg-twice-daily dose. Before and after treatment, the infant stayed at the 50th percentile for weight and length.

Hussain added that, as always, further clinical trials are needed and research involving many more patients will be required.

Correction: This story has been updated to include the correct percentage of time below target range at 13 weeks.

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