Diagnosis and Treatment > Medication
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Summary
Approximately 35% of the pancreatic neuroendocrine tumors (pNETs) are functional, the most common of which is an insulinoma. Rarely can initially nonfunctioning tumor undergo biological transformation to a hormone-secreting tumor with subsequent changes in the clinical picture. We present here three unique patients with long-standing pNETs who developed life-threatening hyperinsulinemic hypoglycemia along with tumor progression. In two of the patients, everolimus (Afinitor) was administered in an attempt to control both tumor growth and hypoglycemia. In two cases everolimus therapy resulted in the abolishment of hypoglycemia and induced significant tumor regression; however these beneficial responses were transient. These cases highlight the exceptional ability of pNETs to change biological behavior in parallel with disease progression. Our experience concurs with recently published studies demonstrating the utility of everolimus for the control of both hypoglycemia and tumor progression.
Learning points
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Nonfunctional pNET can gain new features such as insulin secretion with related morbidity.
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Gain of function in a previously nonfunctional pNET signifies tumor progression and is usually associated with poor prognosis.
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Everolimus proved to be a viable treatment for hypoglycemia in insulinoma patients and was also proven highly effective in the patients presented here.
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As disease progresses, the effect of everolimus on hypoglycemia wanes. We report for the first time the development of hypoglycemia during everolimus treatment.
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Summary
Insulinoma is a rare form of insulin-secreting pancreatic islet cell neuroendocrine (NE) tumor. The medical treatment of the malignant NE disease of the pancreas deeply changed in the last years, thanks to the introduction of new target molecules, as everolimus. Even if the exact mechanism is not actually known, one of the side effects of everolimus, hyperglycemia, has been demonstrated to be useful to contrast the typical hypoglycemia of the insulinoma. We report the case of a patient with a metastatic malignant insulinoma treated with intermittent everolimus, obtaining an important improvement in the quality of life; this suggests the necessity of preclinical studies to analyze the cellular pathways involved in insulin-independent gluconeogenesis.
Learning points
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Effect of somatostatin analogs is long-lasting in the control of functioning NE tumors.
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Persistent everolimus control of hypoglycemia despite serum insulin levels and disease progression.
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Open issue: are disease progression and the increase in serum markers the only valid criteria to reject a treatment?
