Imaging and Diagnostic Challenges in a Patient With Refractory Hypoglycemia Caused by Insulinomas Related to Multiple Endocrine Neoplasia Type 1

Abstract

Insulinoma is a rare neuroendocrine tumor. It may occur sporadically or as part of the genetic tumor syndrome multiple endocrine neoplasia type 1 (MEN1). Diagnosis is challenging because of the small size of insulin producing tumors that lead to hyperinsulinemia. Advances in imaging modalities may provide more accurate diagnosis of primary tumors, metastasis, and tumor functional status. Advances allow for improved medical and surgical management with new tools for research of neuroendocrine tumors. Surgical excision of the primary tumor is often curative; however, insulinomas in MEN1 syndrome are often multifocal with a high rate of recurrence presenting unique challenges in management. Here, we present the case of a 34year-old male with recurrent hypoglycemic episodes and hyperparathyroidism diagnosed with multiple pancreatic insulinomas secondary to MEN1. Furthermore, we provide a brief review of the literature and discuss the approach to diagnosis and management in patients with MEN1 syndrome and future areas of investigation.

Search for germinal mutations in insulin-producing pancreatic tumors

“…и соавт. [88] описан случай инсулиномы в рамках генетически доказанного МЭН1 и синдрома Линча у брата пробанда, что свидетельствует о возможной взаимосвязи генов MEN1 и MLH1; в пользу данного предположения свидетельствует случай развития соматической мутации (c.1546_1547insC) в MEN1 (в ткани аденомы гипофиза) у пациента с синдромом Линча [89].…”

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance

“…Under these circumstances, a fine index of suspicion should be considered, as well as developing a good gastroenterology/endocrinology collaborative [ 97 ]. Also, atypical scenarios are reported raising additional challenges, for instance, individuals with MEN1 manifestations but negative genetic testing, non-functioning NETs (regarding the endocrine panel) that may be more difficult to be identified early unless the carrier status is already confirmed in one individual or a family, and a very aggressive neoplasia behavior with rapid multi-organ spreading [ 96 , 98 , 99 ]. Overall, the gap between the genetic background and the expected clinical picture as well as the sporadic presentation adds more challenges to the complex panel of multiple long-term comorbidities, associated with a reduced quality of life and a general increased syndrome burden including a high mortality that comes from uncontrolled hormonal disease and metastatic tumors (mostly of pancreas origin) [ 76 , 100 , 101 ].…”