A rare entity of malignant insulinoma diagnosed after 30 years of clinical manifestation of hypoglycemia: A case report and literature review

Malignant insulinomas, a rare life threatening pathology, exists in literature as an entity that constitutes 10% of all insulinomas and often present as multi-centric macro nodules with multiple lymph nodes or liver metastases before diagnosis. We report a rather rare case of a 68 year old male with a 30 years history of uninvestigated severe hypoglycemic attacks that improved on glucose intake. Blood tests showed a decreased value of glycemia (45 mg/dL) associated with increased insulin level (54 μU/ml) and an increased glycemia/ insulinemia ratio of 0.83 supporting the diagnosis of insulinoma. Abdominal CT showed a 4 cm mass localized in the head of the pancreas with atrophic body and tail, no signs of distant metastatic disease. A concomitant diagnosis of primary hyperparathyroidism raised, based on elevation of calcium associated and high level of PTH. The coexistence of the two endocrinopathies suggested the presence of type 1 multiple endocrine neoplasia (MEN I). Based on the workup suggesting a benign insulinoma with no signs of metastatic disease, co-existing with debilitating symptoms of hypoglycemia, pancreatectomy with lymph node dissection was performed. Histo-pathological examination returned surprisingly positive for malignant neuro-endocrine tumor with positive lymph nodes. In that domain, we summarized the literature discussion of neuroendocrine tumors, elaborating on malignant insulinoma diagnosis and management. Furthermore, what our article is trying to lay upon existing literature is a case of a long standing existent MEN 1 malignant insulinoma manifesting as a remarkably slow progressive disease of 30 years’ timeline versus a less likely chance of a transformation from benign insulinoma to malignant Keywords: neuroendocrine neoplasm; pancreatectomy; MENI; malignant insulinoma; chronic hypoglycemia.

Clinical characteristics and incidences of benign and malignant insulinoma using a national inpatient database in Japan

Context Insulinoma is the most common pancreatic functional neuroendocrine neoplasm, yet little information on recent clinical practice in patients with insulinoma, especially malignant insulinoma, is available. Objective To clarify the characteristics and practice patterns in patients with insulinoma using a national inpatient database. Methods Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified patients with insulinoma admitted between 2010 and 2018. We compared background characteristics and therapeutic interventions between patients with benign and malignant insulinoma. We also estimated the incidence of insulinoma using the number of patients with newly diagnosed insulinoma in 2012. Results We identified 844 patients with benign insulinoma and 102 patients with malignant insulinoma. Patients with malignant insulinoma were younger (median, 55.5 vs. 66.0 years, P < 0.001) and less likely to be female (55.9% vs. 65.3%, P = 0.061) than patients with benign insulinoma. Analysis of therapeutic interventions revealed that patients with malignant insulinoma more frequently received medications (71.6% vs. 49.6%, P < 0.001) but less frequently underwent pancreatic surgery (57.8% vs. 72.0%, P = 0.003). Older patients were a smaller proportion of those undergoing surgery and a larger proportion of those managed with medications without surgery (P < 0.001). The incidence of insulinoma was estimated to be 3.27 (95% confidence interval, 2.93–3.61) persons per million Japanese adult population per year. Conclusions The present study using a nationwide database had a larger sample size than previous studies and revealed definitive differences in patient characteristics and therapeutic patterns between benign and malignant insulinoma.

Multiple Endocrine Neoplasia Type 1 with Concomitant Existence of Malignant Insulinoma: A Rare Finding

Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome of autosomal dominant inheritance defined by co-occurrence of two or more tumors originating from the parathyroid gland, pancreatic islet cells, and/or anterior pituitary. Insulinoma which has an incidence of 0.4% is a rare pancreatic neuroendocrine tumor. Malignant insulinoma is extremely rare, while primary hyperparathyroidism is a common occurrence in MEN1. We present a case of MEN1 syndrome with 2.6 cm insulinoma in the pancreatic head and parathyroid adenoma in a 56-year-old female who presented with symptoms suggestive of hypoglycemia like multiple episodes of loss of consciousness for four years. Classical pancreaticoduodenectomy was carried out, and the postoperative period was uneventful. Later, subtotal parathyroidectomy was performed, which showed parathyroid adenoma. Patients presenting with features of hypoglycemia should be vigilantly assessed for the presence of a sinister pathology.

Malignant insulinoma hypoglycaemia: complex palliative management

This case presentation describes a 65-year-old woman with metastatic malignant insulinoma who experienced frequent episodes of hypoglycaemia causing significant distress and burden to her quality of life. The report describes how medical management was altered and how the patient was supported in order to alleviate these burdens. In particular, the report highlights the first documented use of flash glucose monitoring in insulinoma, which was beneficial in reducing the discomfort of lancet use and anxiety associated with hypoglycaemic episodes. This case demonstrates the benefits of an individualised approach, collaboration with other specialisms and recommends further evaluation of the use of flash glucose monitoring in palliative care.