Background
Insulinomas are typically benign, solitary, sporadic and surgically cured. Non-MEN1 associated multifocality is rare and has been termed ‘insulinomatosis’. It carries a clinico-pathologic profile distinct from sporadic and MEN1 associated insulinomas.
Case
A 40-year-old female was diagnosed with insulinoma following episodes of hyperinsulinaemic hypoglycaemia. A 12mm head of pancreas benign insulinoma was resected but hypoglycaemia recurred after 7 years. A 10mm head of pancreas benign insulinoma was resected. Hypoglycaemia recurred within 2 months but delayed follow-up culminated in a total pancreatectomy 2 years later. A 28mm head of pancreas benign insulinoma was found alongside insulin-expressing mono-hormonal cell clusters (IMECCs) and islet cell hyperplasia, consistent with insulinomatosis. She was discharged on insulin treatment but this was ceased after several months. Two years later, further hypoglycaemia developed without insulin therapy. There was no identifiable lesion on MRI pancreas, Ga-68 PET or FDG PET. Diazoxide and everolimus were not tolerated and MEN1 testing was negative.
Discussion
Insulinomatosis is a non-MEN1 associated condition resulting in recurrent hyperinsulinaemic hypoglycaemia secondary to multicentric benign insulinomas. It is typified by synchronous and metachronous occurrence of insulinomas with multiple precursor lesions (IMECCs). There is no known genetic defect. In this case, ongoing hypoglycaemia despite total pancreatectomy represents either occult metastases, or de novo microadenomas from unresectable microscopic disease in the pancreatic bed. In insulinomatosis, metastasis is rare and early recurrence is common. Tumours stain monohormonally for insulin unlike MEN1 associated lesions that stain for multiple hormones.
Insulinomatosis should be considered for early recurrent non-MEN-1 associated insulinoma and more extensive resection should be favoured over repeat enucleation to establish the diagnosis.
This is the first reported case of insulinomatosis with persistent hypoglycaemia despite total pancreatectomy. Our case highlights the difficulties in investigating, diagnosing and managing this rare condition.