Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU). 1. Introduction Insulinoma is a rare pancreatic neuroendocrine tumor [1]. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-peptide. Confirmation of neuroendocrine nature of the tumor by immunohistochemistry requires chromogranin and synaptophysin positivity. Metastatic disease can be detected through computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT [2]. Somatostatin receptor scintigraphy may be used not only to document metastatic disease but also as a predictive marker of benefit from therapy with radiolabeled somatostatin analog [3]. The treatment of unresectable metastatic insulinoma is associated with prolonged hospitalization for intravenous glucose infusion. The management of recurrent hypoglycemia also encompasses the administration of diazoxide, hydrochlorothiazide, and glucagon. Sandostatin and its long-acting depot form (Sandostatin LAR) are an adjunct therapy to neuroendocrine tumors. There are a few reports of glycemic control in patients with insulinoma treated with radio labeled somatostatin analogs [4, 5]. The m-TOR inhibitor everolimus has been used
References
[1]
F. J. Service, M. M. McMahon, P. C. O'Brien, and D. J. Ballard, “Functioning insulinoma: incidence, recurrence, and long-term survival of patients: a 60-year study,” Mayo Clinic Proceedings, vol. 66, no. 7, pp. 711–719, 1991.
[2]
D. Wild, J. B. Bomanji, P. Benkert et al., “Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT within patients with gastroenteropancreatic neuroendocrine tumors,” Journal of Nuclear Medicine, vol. 54, no. 3, pp. 364–372, 2013.
[3]
D. J. Kwekkeboom, J. J. Teunissen, W. H. Bakker et al., “Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3] octreotate in patients with endocrine gastroenteropancreatic tumors,” Journal of Clinical Oncology, vol. 23, no. 12, pp. 2754–2762, 2005.
[4]
J. Fischbach, P. Gut, M. Matysiak-Grzes et al., “Combined octreotide and peptide receptor radionuclide therapy ((90)Y-DOTA-TATE) in case of malignant insulinoma,” Neuro Endocrinology Letters, vol. 33, no. 3, pp. 273–278, 2012.
[5]
E. V. Reutova, N. F. Orel, N. S. Besova, E. V. Artemova, N. B. Smirnova, and V. A. Gorbunova, “A case of effective treatment of malignant insulin-producing pancreatic tumor,” Terapevticheskii Arkhiv, vol. 71, no. 10, pp. 44–45, 1999.
[6]
V. Bernard, C. Lombard-Bohas, M. C. Taquet et al., “Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia,” European Journal of Endocrinology, vol. 168, no. 5, pp. 665–674, 2013.
[7]
N. J. Thomas, A. M. Brooke, and G. M. Besser, “Long-term maintenance of normoglycaemia using everolimus in a patient with disseminated insulinoma and severe hypoglycaemia,” Clinical Endocrinology, vol. 78, no. 5, pp. 799–800, 2013.
[8]
A. Rinke, H.-H. Müller, C. Schade-Brittinger et al., “Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID study group,” Journal of Clinical Oncology, vol. 27, no. 28, pp. 4656–4663, 2009.
[9]
T. Katabami, H. Kato, N. Shirai, S. Naito, and N. Saito, “Successful long-term treatment with once-daily injection of low-dose octreotide in an aged patient with insulinoma,” Endocrine Journal, vol. 52, no. 5, pp. 629–634, 2005.
[10]
H. Kishikawa, Y. Okada, A. Hirose, T. Tanikawa, K. Kanda, and Y. Tanaka, “Successful treatment of insulinoma by a single daily dose of octreotide in two elderly female patients,” Endocrine Journal, vol. 53, no. 1, pp. 79–85, 2006.
[11]
E. van Schaik, E. I. van Vliet, R. A. Feelders et al., “Improved control of severe hypoglycemia in patients with malignant insulinomas by peptide receptor radionuclide therapy,” Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 11, pp. 3381–3389, 2011.
