Overview
The goal of this project is to determine the role of FDOPA/PET as a pre-operative diagnostic imaging procedure for differentiating focal and diffuse forms of congenital hyperinsulinism and locating focal lesions in the pancreas to guide surgical resection.
Description
Congenital hyperinsulinism (HI) is the most common cause of recurrent and persistent hypoglycemia, presenting early in infancy. Patients who fail medical therapy usually require resection of the diseased pancreas(partial or subtotal pancreatectomy) to control this disorder. Over half of patients undergoing surgery have a focal area of islet cell dysfunction that is curable with resection. These focal lesions are areas of adenomatosis consisting of a clone of beta-cells that express a paternally-derived mutation of the KATP channel due to loss of heterozygosity for the maternal allele. Current imaging techniques cannot differentiate focal and diffuse forms of hyperinsulinism, nor can they locate focal areas of disease within the pancreas before surgery. L-DOPA is taken up by some neuroendocrine cells, including pancreatic islet cells, and stored as dopamine in secretory granules. Recent studies show that positron emission tomography (PET) following administration of 18F-fluoro-L-DOPA (FDOPA) can distinguish focal and diffuse forms of HI and accurately locate focal lesions within the pancreas.
Eligibility
Inclusion Criteria:
- Any age, but primarily infants 0-6 months given typical age of initial presentation.
- Children with diagnosis of FoHI or DiHI based on clinical criteria (fasting hypoglycemia accompanied by inadequate suppression of plasma insulin, inappropriately low plasma free fatty acid and plasma-hydroxybutyrate concentrations, and an inappropriate glycemic response to glucagon injection)
- confirmed by genetic testing for mutations in ABCC8 and KCNJ1 was1.
- Hypoglycemia uncontrolled with medical management (diazoxide, octreotide).
- Able to withdraw medications in time to wash out prior to the scheduled PET scan.
- Patients fulfilling criteria above but with uncontrolled hypoglycemia after initial surgical management (partial or near-total pancreatectomy)
- Normal hepatic and renal function.
Exclusion Criteria:
- Treatment with other, third-line, medications for hyperinsulinism (nifedipine, glucagon).
- Patients with hepatic or renal insufficiency.
