Clinical outcomes of 20 Japanese patients with insulinoma treated with diazoxide

Abstract

Diazoxide is recognized as an effective medical treatment for insulinoma. However, due to its adverse effects, such as fluid retention, it is sometimes difficult to employ diazoxide at an effective dose in clinical practice. This study aimed to clarify the clinical factors, which may affect efficacy and safety of the diazoxide treatment. We retrospectively evaluated the medical records of 20 patients with insulinoma including 4 malignant cases. The patients were divided into two groups according to the presence or absence of favorable outcomes or adverse effects, and the clinical features of both groups were compared. Diazoxide was effective and ineffective in each 9 patients, respectively. In other 2 cases, the efficacy could not be determined. In the effective group, all patients had benign insulinoma. Additionally, the tumor size determined by imaging test was tended to smaller than the ineffective group but not statistically significant when malignant cases were excluded (p = 0.065). Fluid retention was observed more frequently in females than in males (p = 0.025). Five patients displayed unacceptable thrombocytopenia within a few weeks after the administration of diazoxide. In these patients, the diazoxide dose was significantly higher than that in the other patients [400 mg/day (250-500 mg/day) vs. 225 mg/day (50-425 mg/day), p = 0.027]. These findings may be informative in determining the indication and dose of diazoxide against insulinoma. In addition, a careful evaluation of platelet count would be required for a few weeks after the initiation of diazoxide treatment.

Lanreotide and diazoxide have comparable effects on glucose levels in an elderly Japanese insulinoma patient: a case report

“…Regarding side effects, diazoxide induces fluid retention and thrombocytopenia 2,4) , especially in females 4) , which is consistent with our findings. In contrast, somatostatin analogs can cause malabsorption, cholelithiasis, and hypoglycemia 2) , and inhibit the secretion of counterregulatory hormones, such as glucagon, paradoxically inducing hypoglycemia 2) .…”

“…Approximately three patients per million suffer from insulinoma annually 2 ) ; because Japan is an aging society, the number of elderly patients with insulinoma may increase in the future. This is problematic because, although most insulinomas are benign, curative surgery is the primary treatment 2 , 3 , 4 ) . In the elderly, surgery is not always possible because of aging, disease progression, and comorbidities 5 ) .…”

“…In the elderly, surgery is not always possible because of aging, disease progression, and comorbidities 5 ) . Instead, diazoxide and somatostatin analogs (e.g., octreotide and lanreotide) are sometimes used 2 , 4 ) . Diazoxide, a standard drug for the treatment of insulinomas, acts via ATP-sensitive potassium channels in pancreatic β-cells; however, it often induces fluid retention 4 ) .…”

“…Instead, diazoxide and somatostatin analogs (e.g., octreotide and lanreotide) are sometimes used 2 , 4 ) . Diazoxide, a standard drug for the treatment of insulinomas, acts via ATP-sensitive potassium channels in pancreatic β-cells; however, it often induces fluid retention 4 ) . Somatostatin analogs act via the somatostatin receptor.…”

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

“…He was initially managed with diazoxide, a medication that suppresses insulin secretion by directly opening ATP-dependent potassium channels on the beta-cell membrane. Previous clinical reviews have reported adequate glycemic control using diazoxide in approximately 50% of patients [6]. Medical management is often necessary in the preoperative period or in the management of cases in which surgery is contraindicated.…”