Hyperinsulinisme néonatal persistant: les nouvelles découvertes en pathologie eclairent la pathophysiologie du syndrome et en dirigent l'approche thérapeutique.

Our morphological studies of the pancreas of patients suffering from neonatal persistent hyperinsulinemic hypoglycemia of infancy (PHHI), enabled us to discover the existence of two different forms of the syndrome, focal and diffuse. We defined precise morphological criteria allowing their differential diagnosis, even for intraoperative examination of frozen sections of small biopsies from the various areas of the pancreas. Together with selective venous catheterization, morphology can thus guide the surgeon when deciding between partial pancreatectomy in case of focal PHHI. and near-total pancreatectomy in case of diffuse PHHI. Among neonates affected by PHHI, about 40% suffer from the focal form of the syndrome and have clearly a better prognosis than those suffering from the diffuse form, in that they do not need a subtotal pancreatectomy with its complications. The second part of our work was devoted to analyze the pathogenesis of PHHI. We demonstrated that diffuse PHHI is not the result of an abnormal proliferation of b cells, and thus that nesidioblastosis is not the underlying pathological condition of the disease. By contrast, in total concordance with its genetic background, the focal PHHI lesion has a very high proliferation index, not observed in insulinomas, the other pancreatic endocrine lesion responsible for hyperinsulinemia. Comparing the focal lesion in focal PHHI with insulinomas, we found that not only their morphological features are different, but also their functional characteristics studied by morphological and quantitative approaches. However, some insulinomas share similarities in their molecular background with focal PHHI. Finally, we recently identified an atypical form of PHHI, characterized by a mosaicism of islets. This new form is currently under investigation.