Double Trouble: When Focal and Diffuse Hyperinsulinism Occur Simultaneously

Congenital hyperinsulinism (HI) may be diazoxide-responsive or diazoxide-unresponsive. Patients with diazoxide-unresponsive HI are further classified based on having the diffuse or focal form of the disease, with different management strategies associated with each form. While patients with HI typically have only one form of the disease, here we report 3 patients who had both focal and diffuse HI.

Three patients with diazoxide-unresponsive HI were transferred to our hospital for further management. All 3 patients had genetic testing which was equivocal or initially negative. Given their diazoxide status and not wanting to miss a focal lesion that was amenable to a surgical cure, all 3 patients underwent imaging with 18 F-L 3,4-dihydroxyphenylalanine positron emission tomography which identified focal pancreatic lesions in all 3 patients. They all had surgical resection of the lesions. Biopsies of the pancreas outside of the lesions noted rare or scattered islet cell nucleomegaly, indicative of diffuse disease, and subsequent fasting studies to determine if patients were cured revealed ongoing HI. Further review of genetic results suggested a mechanism for both focal and diffuse HI occurring in each of the patients. For all 3 patients, their ongoing HI could be managed with diazoxide following removal of the focal lesion.

Focal and diffuse HI can occur in the same patient. Following resection of focal pancreatic lesions, the patients require careful evaluations for evidence of ongoing HI, and depending on the genetic results, diazoxide may be a management option for ongoing HI in a subset of these patients.