Diazoxide treatment for insulinoma: a national UK survey

Gill, Geoffrey; Rauf, O.; MacFarlane, I A

doi:10.1136/pgmj.73.864.640

Cited by 148 publications

(116 citation statements)

References 4 publications

(1 reference statement)

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“…20 Some patients have gastrointestinal intolerance to the drug and in very high doses it may produce anorexia. 21 We have found that a small initial dose with an increase of Յ 300 -400 mg per day over 3-4 weeks is the most effective way to initiate and maintain therapy. All the other forms of therapy shown in Table 2 have either had no benefit or relatively short-term benefit and most, such as chemotherapy regimens, are toxic and of little benefit.…”

Section: Discussionmentioning

confidence: 99%

Malignant insulinoma

Hirshberg

Cochran

Skarulis

et al. 2005

Cancer

144

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BACKGROUNDMalignant insulinoma occurs in a few patients with insulinoma. Due to the small sample of patients, there are little data regarding their clinical manifestation as well as the preferred treatment modalities. The aims of the current study were to summarize the National Institutes of Health experience during the last two decades and to conduct a critical review of the current literature.METHODSThe authors identified 10 patients with metastatic insulinoma.RESULTSThe patients presented with four patterns of clinical behavior. First, four patients presented with lymph node metastasis and, after surgical excision, maintained a prolonged tumor‐free survival. Second, four patients presented with metastatic disease to the liver, which appeared years after the initial diagnosis and presumed curative surgery. Third, one patient presented with a large α‐fetoprotein‐secreting liver mass. Finally, 9 of the 10 patients had a prolonged survival. Various treatment modalities were used to control hypoglycemia. Short‐term benefits were most often achieved with embolization and diazoxide. Less successful modalities included radiofrequency ablation, radical debulking surgery, verapamil therapy, octreotide therapy, and chemotherapy.CONCLUSIONSThe current study, as well as others, suggested that metastatic insulinoma may have a variable natural history. After the initial surgical resection, the biology of the tumor, rather than any treatment modality, was most likely the major determinant of long‐term survival. Cancer 2005. © Published 2005 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Malignant insulinoma

Hirshberg

Cochran

Skarulis

et al. 2005

Cancer

144

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“…Recent recommendations suggest the use of everolimus as an alternative to chemotherapy as the first line of antitumor systemic therapy in the case of progressive malignant insulinomas (31). Diazoxide therapy is the oldest antisecretory medical option that is still largely prescribed, even if data are lacking regarding the duration of its benefit and tolerance in the long run in malignant insulinoma (32,33). Somatostatin analog efficacy in the control of hypoglycemic symptoms has also been reported in malignant insulinoma, mainly in case reports.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

Bernard

Lombard‐Bohas

Taquet

et al. 2013

European Journal of Endocrinology

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Background: Refractory hypoglycemia in patients with metastatic insulinoma is an important cause of morbidity and mortality. Everolimus could be a new therapeutic option. Methods: Within the French Group, we conducted a retrospective, multicentric study of endocrine tumors to evaluate the time to the first recurrence of symptomatic hypoglycemia, after everolimus initiation, in patients with metastatic insulinoma and refractory hypoglycemia. Ongoing hyperglycemic medical options, tumor response, and safety information were recorded. Results: Twelve patients with metastatic insulinoma and refractory hypoglycemia who were treated with everolimus between May 2007 and June 2011 were reviewed. Everolimus (starting dose, 10 mg/day, except in one patient, 5 mg/day) was given after a median of four previous therapeutic lines. Medication aimed at normalizing blood glucose levels in 11 patients. After a median duration of 6.5 months (range 1-35C months), median time to the first recurrence of symptomatic hypoglycemia was 6.5 months (range 0 to 35C months). Three patients discontinued everolimus because of cardiac and/or pulmonary adverse events at 1, 1.5, and 7 months after initiation, which led to two deaths. Three patients discontinued everolimus because of tumor progression at 2, 3, and 10 months after initiation, without recurrence of hypoglycemia. Conclusion: Everolimus appears to be a new effective treatment for patients with metastatic insulinoma and refractory hypoglycemia. Tolerance should be carefully monitored.

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“…Oversecretion of insulin from insulinomas can usually be treated by a combination of somatostatin and diazoxide. 28,29 Diazoxide has also been used to "rest" β-cells in newly diagnosed type 1 diabetics and demonstrated a persistent effect in preserving a small fraction of functional β-cells that would have been lost without treatment. 12,30 However, the use of diazoxide is fraught with side effects, probably due to its low Kir6.2/SUR1 selectivity.…”

Section: Discussionmentioning

confidence: 99%

Establishment and Application of in Vitro Membrane Potential Assays in Cell Lines with Endogenous or Recombinant Expression of ATP-Sensitive Potassium Channels (Kir6.2/SUR1) Using a Fluorescent Probe Kit

Arkhammar¹,

Wahl²,

Gerlach³

et al. 2004

SLAS Discovery

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The flow of current through the adenosine triphosphate (ATP)-sensitive potassium channel (K ATP ) of the isoform Kir6.2/ SUR1 regulates the resting membrane potential in the pancreatic β-cell. In combination with the cellular glucose metabolism, it is an important minute-to-minute regulator of insulin secretion and whole-body glucose homeostasis. The same K ATP isoform is further reported to be present in glucagon-secreting α-cells, intestinal L-cells, and glucose-responsive neurons in the hypothalamus. All in all, this makes Kir6.2/SUR1 an interesting drug target. Using a commercially available fluorescent membrane potential probe kit and a conventional 96-well fluorescence plate reader, the authors have developed and established qualitative membrane potential assays used to screen for potassium channel closers (KCCs) and openers (KCOs) in insulin-and glucagon-secreting cell lines as well as in cells with recombinant expression of the human Kir6.2/ SUR1 channel complex. Both glucose-and KCC-induced depolarization could be demonstrated. The magnitudes of these responses and KCO-induced repolarization at high glucose displayed some variation between the different cell lines but a similar rank order of test compounds. Some cell types required the presence of a KCC, such as tolbutamide, to display significant effects of KCOs. The authors find that robust and reliable functional in vitro assays compatible with medium-throughput screening and high-throughput screening can be developed as a base for finding new, more potent, and isoform-selective

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Diazoxide treatment for insulinoma: a national UK survey

Cited by 148 publications

References 4 publications

Malignant insulinoma

Malignant insulinoma

Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

Establishment and Application of in Vitro Membrane Potential Assays in Cell Lines with Endogenous or Recombinant Expression of ATP-Sensitive Potassium Channels (Kir6.2/SUR1) Using a Fluorescent Probe Kit

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