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This version published online on June 30, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-0788
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Submitted on April 10, 2009
Accepted on June 23, 2009

Successful Control of Intractable Hypoglycemia Using Rapamycin in an 86-year old man with a Pancreatic Insulin-Secreting Islet Cell Tumor and Metastases

Matthew E. Bourcier MPA, PA-C*, Amanda Sherrod MS, Margaret DiGuardo BA, and Aaron I. Vinik M.D., Ph.D.

Strelitz Diabetes Center and Neuroendocrine Unit, Department of Internal Medicine, Eastern Virginia Medical School (M.E.B., A.S., M.D., A.I.V.), Norfolk, Virginia 23510

* To whom correspondence should be addressed. E-mail: bourcime{at}evms.edu.

Context: Insulinomas are rare tumors of the pancreatic islet cells that produce insulin. Approximately 5 to 10% of these tumors are cancerous and control of insulin secretion and hypoglycemia may be difficult in these patients. Malignant insulinomas generally respond poorly to traditional chemotherapeutic agent regimens. At present, streptozotocin (STZ) is the only approved drug for the treatment of pancreatic islet cell tumors.

Setting and Patient: This report describes a case of an elderly gentleman with a metastatic pancreatic insulinoma and severe hypoglycemia. A continuous infusion of octreotide lowered the blood glucose levels further. He required diazoxide, a thiazide diuretic, phenytoin and a constant infusion of glucose to control the hypoglycemia and elevated insulin levels.

Intervention: Rapamycin at an oral dose of 2 mg a day.

Results: On the mTOR (mammalian target of rapamycin) agent rapamycin he was weaned off all drugs except for the thiazide diuretic and maintained euglycemia with a reduction of circulating insulin levels. He remains euglycemic for the past year with no evidence of tumor progression based on Octreoscan®. His quality of life is excellent and he remains active having recently completed a triathlon.

Conclusions: Rapamycin may provide a useful means of abrogating tumor growth and controlling hypoglycemia in malignant insulinomas by reducing the malignant beta cell growth and proliferation as well as inhibiting insulin production.


Key words: Sirolimus (rapamycin) • mTOR (mammalian target of rapamycin) • Hypoglycemia • Metastatic pancreatic islet cell tumors • Insulin hypersecretion







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