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Published in: BMC Endocrine Disorders 1/2018

Open Access 01-12-2018 | Case report

A case of malignant insulinoma responsive to somatostatin analogs treatment

Authors: Mariasmeralda Caliri, Valentina Verdiani, Edoardo Mannucci, Vittorio Briganti, Luca Landoni, Alessandro Esposito, Giulia Burato, Carlo Maria Rotella, Massimo Mannelli, Alessandro Peri

Published in: BMC Endocrine Disorders | Issue 1/2018

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Abstract

Background

Insulinoma is a rare tumour representing 1–2% of all pancreatic neoplasms and it is malignant in only 10% of cases. Locoregional invasion or metastases define malignancy, whereas the dimension (> 2 cm), CK19 status, the tumor staging and grading (Ki67 > 2%), and the age of onset (> 50 years) can be considered elements of suspect.

Case presentation

We describe the case of a 68-year-old man presenting symptoms compatible with hypoglycemia. The symptoms regressed with food intake. These episodes initially occurred during physical activity, later also during fasting. The fasting test was performed and the laboratory results showed endogenous hyperinsulinemia compatible with insulinoma. The patient appeared responsive to somatostatin analogs and so he was treated with short acting octreotide, obtaining a good control of glycemia. Imaging investigations showed the presence of a lesion of the uncinate pancreatic process of about 4 cm with a high sst2 receptor density. The patient underwent exploratory laparotomy and duodenocephalopancreasectomy after one month.
The definitive histological examination revealed an insulinoma (T3N1MO, AGCC VII G1) with a low replicative index (Ki67: 2%).

Conclusions

This report describes a case of malignant insulinoma responsive to octreotide analogs administered pre-operatively in order to try to prevent hypoglycemia. The response to octreotide analogs is not predictable and should be initially assessed under strict clinical surveillance.
Literature
1.
go back to reference Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19:753–81.CrossRef Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19:753–81.CrossRef
2.
go back to reference Hirshberg B, Cochran C, Skarulis MC, Libutti SK, Alexander HR, Wood BJ, et al. Malignant insulinoma: spectrum of unusual clinical features. Cancer. 2005;104:264–72.CrossRef Hirshberg B, Cochran C, Skarulis MC, Libutti SK, Alexander HR, Wood BJ, et al. Malignant insulinoma: spectrum of unusual clinical features. Cancer. 2005;104:264–72.CrossRef
3.
4.
go back to reference Jonkers YM, Claessen SM, Veltman JA, Geurts van Kessel A, Din-jens WN, Skogseid B, et al. Molecular parameters associated with insulinoma progression: chromosomal instability versus p53 and CK19 status. Cytogenet Genome Res. 2006;115:289–97.CrossRef Jonkers YM, Claessen SM, Veltman JA, Geurts van Kessel A, Din-jens WN, Skogseid B, et al. Molecular parameters associated with insulinoma progression: chromosomal instability versus p53 and CK19 status. Cytogenet Genome Res. 2006;115:289–97.CrossRef
5.
go back to reference Pape UF, Berndt U, Müller-Nordhorn J, Böhmig M, Roll S, Koch M, et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer. 2008;15:1083–97.CrossRef Pape UF, Berndt U, Müller-Nordhorn J, Böhmig M, Roll S, Koch M, et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer. 2008;15:1083–97.CrossRef
6.
go back to reference Pape UF, Jann H, Müller-Nordhorn J, Bockelbrink A, Berndt U, Willich SN, et al. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer. 2008;113:256–65.CrossRef Pape UF, Jann H, Müller-Nordhorn J, Bockelbrink A, Berndt U, Willich SN, et al. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer. 2008;113:256–65.CrossRef
7.
go back to reference E B, Caron P, Lombard-Bohas C, Tabarin A, Mitry E, Reznick Y, et al. Malignant insulinoma: recommendations for characterisation and treatment. Ann Endocrinol. 2013;74:523–33.CrossRef E B, Caron P, Lombard-Bohas C, Tabarin A, Mitry E, Reznick Y, et al. Malignant insulinoma: recommendations for characterisation and treatment. Ann Endocrinol. 2013;74:523–33.CrossRef
8.
go back to reference Perren A, Wiesli P, Schmid S, Montani M, Schmitt A, Schmid C, et al. Pancreatic endocrine tumors are a rare manifestation of the neurofibromatosis type 1 phenotype: molecular analysis of a malignant insulinoma in a NF-1 patient. Am J Surg Pathol. 2006;30:1047–51.CrossRef Perren A, Wiesli P, Schmid S, Montani M, Schmitt A, Schmid C, et al. Pancreatic endocrine tumors are a rare manifestation of the neurofibromatosis type 1 phenotype: molecular analysis of a malignant insulinoma in a NF-1 patient. Am J Surg Pathol. 2006;30:1047–51.CrossRef
9.
go back to reference Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, Service FJ, Endocrine Society. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2009;94:709–28.CrossRef Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, Service FJ, Endocrine Society. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2009;94:709–28.CrossRef
10.
go back to reference Vezzosi D, Bennet A, Rochaix P, Courbon F, Selves J, Pradere B, et al. Octreotide in insulinoma patients: efficacy on hypoglycemia, relationships with octreosacan scintigraphy and immunostaining with anti-sst2A and anti-sst5 antibodies. Eur J Endocrinol. 2005;152:757–67.CrossRef Vezzosi D, Bennet A, Rochaix P, Courbon F, Selves J, Pradere B, et al. Octreotide in insulinoma patients: efficacy on hypoglycemia, relationships with octreosacan scintigraphy and immunostaining with anti-sst2A and anti-sst5 antibodies. Eur J Endocrinol. 2005;152:757–67.CrossRef
11.
go back to reference Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, et al. The 2016 update of the international study group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161:584–91.CrossRef Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, et al. The 2016 update of the international study group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161:584–91.CrossRef
12.
go back to reference Whipple AO. The surgical therapy of hyperinsulinism. J Int Chir. 1938;3:237–76. Whipple AO. The surgical therapy of hyperinsulinism. J Int Chir. 1938;3:237–76.
13.
go back to reference Cryer PE. Symptoms of hypoglycemia, thresholds for their occurrence, and hypoglycemia unawareness. Endocrinol Metab Clin N Am. 1999;28:495–500.CrossRef Cryer PE. Symptoms of hypoglycemia, thresholds for their occurrence, and hypoglycemia unawareness. Endocrinol Metab Clin N Am. 1999;28:495–500.CrossRef
14.
go back to reference Murad MH, Coto-Yglesias F, Wang AT, Sheidaee N, Mullan RJ, Elamin MB, et al. Clinical review: drug-induced hypoglycemia: a systematic review. J Clin Endocrinol Metab. 2009;94:741–5.CrossRef Murad MH, Coto-Yglesias F, Wang AT, Sheidaee N, Mullan RJ, Elamin MB, et al. Clinical review: drug-induced hypoglycemia: a systematic review. J Clin Endocrinol Metab. 2009;94:741–5.CrossRef
15.
go back to reference Nieman LK, Chanco Turner M. Addison’s disease. Clin Dermatol. 2006;276–80. Nieman LK, Chanco Turner M. Addison’s disease. Clin Dermatol. 2006;276–80.
16.
go back to reference A M, Fanelli C, Veneman T, Perriello G, Calderone S, Platanisiotis D, et al. Reversibility of unawareness of hypoglycemia in patients with insulinomas. N Engl J Med. 1993;329:834–9.CrossRef A M, Fanelli C, Veneman T, Perriello G, Calderone S, Platanisiotis D, et al. Reversibility of unawareness of hypoglycemia in patients with insulinomas. N Engl J Med. 1993;329:834–9.CrossRef
17.
go back to reference Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri R. Insulin autoimmune syndrome (Hirata disease) in European Caucasians taking α-lipoic acid. Clin Endocrinol. 2014;81:204–9.CrossRef Gullo D, Evans JL, Sortino G, Goldfine ID, Vigneri R. Insulin autoimmune syndrome (Hirata disease) in European Caucasians taking α-lipoic acid. Clin Endocrinol. 2014;81:204–9.CrossRef
18.
go back to reference Raffel A, Raffel A, Krausch MM, Anlauf M, Wieben D, Braunstein S, Klöppel G, et al. Diffuse nesidioblastosis as a cause of hyperinsulinemic hypoglycemia in adults: a diagnostic and therapeutic challenge. Surgery. 2007;141:179–84.CrossRef Raffel A, Raffel A, Krausch MM, Anlauf M, Wieben D, Braunstein S, Klöppel G, et al. Diffuse nesidioblastosis as a cause of hyperinsulinemic hypoglycemia in adults: a diagnostic and therapeutic challenge. Surgery. 2007;141:179–84.CrossRef
19.
go back to reference Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Ito S, Ogawa Y, et al. Diagnosis and management of insulinoma. World J Gastroenterol. 2013;19:829–37.CrossRef Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Ito S, Ogawa Y, et al. Diagnosis and management of insulinoma. World J Gastroenterol. 2013;19:829–37.CrossRef
20.
go back to reference Shi W, Johnston CF, Buchanan KD, Ferguson WR, Laird JD, Crothers JG, Mcilrath EM. Localization of neuroendocrine tumours with [111In] DTPAoctreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging. Q J Med. 1998;91:295–301.CrossRef Shi W, Johnston CF, Buchanan KD, Ferguson WR, Laird JD, Crothers JG, Mcilrath EM. Localization of neuroendocrine tumours with [111In] DTPAoctreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging. Q J Med. 1998;91:295–301.CrossRef
21.
go back to reference Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993;20:716–31.CrossRef Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993;20:716–31.CrossRef
22.
go back to reference de Herder WW, Kwekkeboom DJ, Valkema R, Feelders RA, van Aken MO, Lamberts SW, et al. Neuroendocrine tumors and somatostatin: imaging techniques. J Endocrinol Investig. 2005;28:132–6. de Herder WW, Kwekkeboom DJ, Valkema R, Feelders RA, van Aken MO, Lamberts SW, et al. Neuroendocrine tumors and somatostatin: imaging techniques. J Endocrinol Investig. 2005;28:132–6.
23.
go back to reference Schillaci O, Massa R, Scopinaro F. 111In-pentetreotide scintigraphy in the detection of insulinomas: importance of SPECT imaging. J Nucl Med. 2000;41:459–62.PubMed Schillaci O, Massa R, Scopinaro F. 111In-pentetreotide scintigraphy in the detection of insulinomas: importance of SPECT imaging. J Nucl Med. 2000;41:459–62.PubMed
24.
go back to reference Christ E, Wild D, Forrer F, Brändle M, Sahli R, Clerici T, et al. Glucagon-like peptide-1 receptor imaging for localization of insulinomas. J Clin Endocrinol Metab. 2009;94:4398–444.CrossRef Christ E, Wild D, Forrer F, Brändle M, Sahli R, Clerici T, et al. Glucagon-like peptide-1 receptor imaging for localization of insulinomas. J Clin Endocrinol Metab. 2009;94:4398–444.CrossRef
25.
go back to reference Sundin A, Arnold R, Baudin E, Cwikla JB, Eriksson B, Fanti S, et al. ENETS consensus guidelines for the standards of Care in Neuroendocrine Tumors: radiological, Nuclear Medicine & Hybrid Imaging. Neuroendocrinology. 2017;105:212–44.CrossRef Sundin A, Arnold R, Baudin E, Cwikla JB, Eriksson B, Fanti S, et al. ENETS consensus guidelines for the standards of Care in Neuroendocrine Tumors: radiological, Nuclear Medicine & Hybrid Imaging. Neuroendocrinology. 2017;105:212–44.CrossRef
26.
go back to reference Gill GV, Rauf O, MacFarlane IA. Diazoxide treatment for insulinoma: a national UK survey. Postgrad Med J. 1997;73:640–1.CrossRef Gill GV, Rauf O, MacFarlane IA. Diazoxide treatment for insulinoma: a national UK survey. Postgrad Med J. 1997;73:640–1.CrossRef
27.
go back to reference Matej A, Bujwid H, Wroński J. Glycemic control in patients with insulinoma. Hormones (Athens). 2016;15:489–99.CrossRef Matej A, Bujwid H, Wroński J. Glycemic control in patients with insulinoma. Hormones (Athens). 2016;15:489–99.CrossRef
28.
go back to reference Romeo S, Milione M, Gatti A, Fallarino M, Corleto V, Morano S, Baroni MG. Complete clinical remission and disappearance of liver metastases after treatment with somatostatin analogue in a 40-year-old woman with a malignant insulinoma positive for somatostatin receptors type 2. Horm Res. 2006;65:120–5.PubMed Romeo S, Milione M, Gatti A, Fallarino M, Corleto V, Morano S, Baroni MG. Complete clinical remission and disappearance of liver metastases after treatment with somatostatin analogue in a 40-year-old woman with a malignant insulinoma positive for somatostatin receptors type 2. Horm Res. 2006;65:120–5.PubMed
29.
go back to reference Usukura M, Yoneda T, Oda N, Yamamoto Y, Takata H, Hasatani K, Takeda Y. Medical treatment of benign insulinoma using octreotide LAR: a case report. Endocr J. 2007;54:95–101.CrossRef Usukura M, Yoneda T, Oda N, Yamamoto Y, Takata H, Hasatani K, Takeda Y. Medical treatment of benign insulinoma using octreotide LAR: a case report. Endocr J. 2007;54:95–101.CrossRef
30.
go back to reference Jawiarczyk A, Bolanowski M, Syrycka J, Bednarek-Tupikowska G, Kałużny M, Kołodziejczyk A, Domosławski P. Effective therapy of insulinoma by using long-acting somatostatin analogue. A case report and literature review. Exp Clin Endocrinol Diabetes. 2012;120:68–72.CrossRef Jawiarczyk A, Bolanowski M, Syrycka J, Bednarek-Tupikowska G, Kałużny M, Kołodziejczyk A, Domosławski P. Effective therapy of insulinoma by using long-acting somatostatin analogue. A case report and literature review. Exp Clin Endocrinol Diabetes. 2012;120:68–72.CrossRef
31.
go back to reference Baudin E, Caron P, Lombard-Bohas C, Tabarin A, Mitry E, Reznick Y, et al. Malignant insulinoma: recommendations for characterisation and treatment. Ann Endocrinol (Paris). 2013;74:523–33.CrossRef Baudin E, Caron P, Lombard-Bohas C, Tabarin A, Mitry E, Reznick Y, et al. Malignant insulinoma: recommendations for characterisation and treatment. Ann Endocrinol (Paris). 2013;74:523–33.CrossRef
32.
go back to reference Stehouwer CDA, Lems WF, Fischer HRA, Hackeng WHL, Naafs MAB. Aggravation of hypoglycemia in insulinoma patients by the long-acting somatostatin analogue octreotide (Sandostatin). Acta Endocrinol. 1989;121:34–40.CrossRef Stehouwer CDA, Lems WF, Fischer HRA, Hackeng WHL, Naafs MAB. Aggravation of hypoglycemia in insulinoma patients by the long-acting somatostatin analogue octreotide (Sandostatin). Acta Endocrinol. 1989;121:34–40.CrossRef
33.
go back to reference Appetecchia M, Baldelli R. Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives. J Exp Clin Cancer Res. 2010;29:19.CrossRef Appetecchia M, Baldelli R. Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives. J Exp Clin Cancer Res. 2010;29:19.CrossRef
Metadata
Title
A case of malignant insulinoma responsive to somatostatin analogs treatment
Authors
Mariasmeralda Caliri
Valentina Verdiani
Edoardo Mannucci
Vittorio Briganti
Luca Landoni
Alessandro Esposito
Giulia Burato
Carlo Maria Rotella
Massimo Mannelli
Alessandro Peri
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2018
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-018-0325-4

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