Glycemic control in patients with insulinoma

Abstract

Insulinoma is the most common neuroendocrine tumor of the pancreas. surgical management of insulinomas is considered to be the only curative method. however, effective glycemic control preoperatively and in unresectable insulinomas remains a significant issue. hyperinsulinism, occurring as a result of the hormone-secreting tumor, leads to life-threatening hypoglycemia episodes which require urgent medical treatment. This article discusses current management of hypoglycemia in insulinoma patients, including: education and lifestyle modifications, pharmacotherapy (diazoxide, somatostatin analogs, mTor inhibitor -everolimus), cytoreductive methods and continuous glucose monitoring systems.

Successful Long-Term Medical Management of Unresectable Insulinomas

“…Diazoxide is considered first-line medical therapy for symptom control, inhibiting release of insulin from β-cells by activating potassium channels [1][2][3][4]. With Patient 1, long-acting octreotide was used first-line with great efficacy.…”

“…Their efficacy may depend on SSTR subtype expression on the specific insulinoma [4]. They are considered second-line medical therapy for benign insulinomas; however, due to antiproliferative and antitumoral activity, they can be used first-line for malignant insulinomas [1,4,6]. Use of everolimus was considered during her recurrence, but was deferred, since her symptoms were controlled on octreotide and follow-up imaging was stable.…”

“…For Patient 2, the use of diazoxide caused side effects. Roughly half of patients experience side effects, including fluid retention, hirsutism, gastrointestinal symptoms, rash, and palpitations [1,4]. Her fluid retention necessitated use of HCTZ.…”

“…Insulinomas are functional pancreatic neuroendocrine tumors (pNETs), derived from insulin-secreting β-cells of the pancreas. Estimated incidence is 1-4 new cases per million persons annually [1,2]. The majority are benign, solitary tumors, less than 2 cm in diameter.…”

A farnesyl transferase inhibitor induces apoptosis of insulinoma pancreatic β cells of mouse

“…When using drugs to induce cell death, it must be taken into consideration about the possibility that the sudden death of a large amount of insulinoma cells in a patient might release too much insulin and cause fatal hypoglycemia [40][41][42][43][44][45][46]. However, this may not be a problem for R115777 therapy because it induces tumor cell apoptosis and the apoptotic cells or apoptotic bodies are engulfed by macrophages through phagocytosis and the insulin inside the dead cells/bodies will most possibly be degraded by the lysosomal enzymes of the macrophages [47][48][49][50].…”