Diagnosis and Treatment of Insulinoma: an up-to-date Overview

Year 2017, Volume: 6 Issue: 1, 32 - 37, 01.01.2017

Esra Ademoğlu Zehra Candan Hikmet Tekçe

https://doi.org/10.5505/abantmedj.2017.24892

Abstract

Insulinoma is a rare endocrine tumor derived from pancreatic β–cells and the most common cause of organic hyperinsulinemic hypoglycemia. It is usually a small, solitary, intrapancreatic, and benign tumor. It is generally seen as sporadic cases, but it can also be associated with multiple endocrine neoplasia type 1 syndrome MEN-1 . Distinction between malignant and benign tumor can only made by the presence of metastasis as there are no specific morphologic, biochemical or genetic features distinguishing them. Several invasive and non-invazive procedures are present for localization of tumor. Once the localization of tumor is determined, excision can be curative as more than 90% of insulinomas are benign lesions and enucleation is generally sufficient. The treatment includes systemic chemotherapy, chemoembolization, cryotherapy and peptide radionuclide treatment in cases which cannot be operated.

Keywords

Insulin, C peptide, Hypoglycemia

İnsülinoma Tanı ve Tedavisi: Güncel Bakış

Abstract

İnsülinoma, pankreas beta hücrelerinden köken alan nadir görülen bir endokrin tümördür ve organik hiperinsülinemik hipogliseminin en sık nedenidir. Çoğunlukla küçük, soliter, intrapankreatik ve benign bir tümördür. Genellikle sporodik olarak görülür ancak multıpl endokrin neoplazi sendromu MEN-1 ile de birliktelik gösterebilir. Malign ve benign tümör ayrımını sağlayan spesifik morfolojik, biyokimyasal veya genetik özellikler olmadığı için malignite tanısı lokal ve uzak metastaz varlığı ile konur. Lokalizasyonda girişimsel ve girişimsel olmayan birçok yöntem mevcuttur. Tümör lokalize edildikten sonra cerrahi tedavi ile tümörün çıkarılması olguların %90’ından fazlası benign olduğu için küratiftir ve genelde enükleasyon yeterli olmaktadır. Opere edilemeyen malign insülinomalarda tedavi sistemik kemoterapi, kemoembolizasyon, kriyoterapi ve peptid radyonüklid tedaviyi içerir.

Keywords

İnsülin, C peptid, Hipoglisemi

References

• Service FJ, McMahon MM, O'Brien PC, Ballard DJ. Functioning insulinoma, incidence, recurrence, and long- term survival of patients: a 60-year study. Mayo Clin Proc. 1991 Jul;66(7):711-9.
• Dixon E, Pasieka JL. Functioning and nonfunctioning neuroendocrine tumors of the pancreas. Curr Opin Oncol. 2007 Jan;19(1):30-5.
• Demeure MJ, Klonoff DC, Karam JH, Duh QY, Clark OH. Insulinomas associated with multiple endocrine neoplasia type I: the need for a different surgical approach. Surgery. 1991 Dec;110(6):998-1004.
• Whipple AO, Frantz VK. Adenoma of islet cells with hyperinsulinism: A review. Ann Surg. 1935 Jun;101(6):1299-335.
• Wilder RM, Allan FN, Power MH,. Robertson H.E. Carcinoma of the islets of the pancreas: hyperinsulinism and hypoglycemia. J Am Med Assoc, 89 (1927), pp. 348– 55.
• Dizon AM, Kowalyk S, Hoogwerf BJ. Neuroglycopenic and other symptoms in patients with insulinomas. Am J Med. 1999 Mar;106(3):307-10.
• 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 Mar;94(3):709-28.
• Grant CS, van Heerden J, Charboneau JW, James EM, Reading CC. Insulinoma. The value of intraoperative ultrasonography. Arch Surg. 1988 Jul;123(7):843-8.
• Doherty GM, Doppman JL, Shawker TH, Miller DL, Eastman RC, Gorden P, Norton JA. Results of a prospective strategy to diagnose, localize, and resect insulinomas. Surgery. 1991 Dec;110(6):989-96.
• Noone TC, Hosey J, Firat Z, Semelka RC. İmaging and localization of islet-cell tumours of the pancreas on CT and MRI. Best Pract Res Clin Endocrinol Metab. 2005 Jun;19(2):195-211.
• Mirallié E, Pattou F, Malvaux P, Filoche B, Godchaux JM, Maunoury V, Palazzo L, Lefebvre J, Huglo D, Paris JC, Carnaille B, Proye C. Value of endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localization of insulinomas and gastrinomas. Experience of 54 cases. Gastroenterol Clin Biol. 2002;26(4):360-6.
• Christ E, Wild D, Forrer F, Brändle M, Sahli R, Clerici T, Gloor B, Martius F, Maecke H, Reubi JC Glucagon-like peptide-1 receptor imaging for localization of insulinomas. J Clin Endocrinol Metab. 2009;94(11):4398- 405.
• Chee YC, Heng A, Tan KP, Singh GD. A case of insulinoma diagnosed by plasma insulin, selective pancreatic angiography and computerised tomography. Ann Acad Med Singapore. 1981 Apr;10(2):221-5.
• Kinoshita Y, Nonaka H, Suzuki S, Kondo T, Chihara K, Chiba T, Fujita T, Kotoura Y, Yamamura T. Accurate localization of insulinoma using percutaneous transhepatic portal venous sampling--usefulness of simultaneous measurement of plasma insulin and glucagon levels. Clin Endocrinol (Oxf). 1985 Nov;23(5):587-93.
• Zimmer T, Scherübl H, Faiss S, Stölzel U, Riecken EO, Wiedenmann B. Endoscopic ultrasonography of neuroendocrine tumours. Digestion. 2000;62 Suppl 1:45- 50.
• Placzkowski KA, Vella A, Thompson GB, Grant CS, Reading CC, Charboneau JW, Andrews JC, Lloyd RV, Service FJ. Secular trends in the presentation and management of functioning insulinoma at the Mayo Clinic, 1987-2007. J Clin Endocrinol Metab. 2009;94(4):1069-73.
• Ishii H, Ito T, Moriya S, Horie Y, Tsuchiya M. Insulinoma a statistical review of 443 cases in Japan. Nihon Rinsho. 1993 Jan;51 Suppl:199-206.
• Sakurai A, Aizawa T, Katakura M, Sato Y, Kaneko G, Yoshizawa K, Hashizume K. Insulinoma in a patient with non-insulin-dependent diabetes mellitus. Endocr J. 1997 Aug;44(4):473-7.
• Ravnik-Oblak M, Janez A, Kocijanicic A. Insulinoma induced hypoglycemia in a type 2 diabetic patient.Wien Klin Wochenschr. 2001 Apr 30;113(9):339-41.
• Lablanche S, Chobert-Bakouline M, Risse O, Laverrière MH, Chabre O, Benhamou PY Malignant insulinoma may arise during the course of type 1 diabetes mellitus: A case report. Diabetes Metab. 2015 Jun;41(3):258-61.
• Campos-Olive N, Ferrer-Garcia JC, Safont MJ. Malignant insulinoma in a patient with type 2 diabetes mellitus. Acta Endo (Buc). 2010, 6 (1): 103-9.
• Hirshberg B. Cochran C., Skarulis MC, Libutti SK, Alexander HR, Wood BJ, Chang R, Kleiner DE, Gorden P. Malignant insulinoma: spectrum of unusual clinical features. Cancer 2005 Jul;104(2):264-72.
• Baudin E, Caron P, Bohas CL, Tabarin A, Mitry E, Reznick Y, Taieb D, Pattou F, Goudet P, Vezzosi D. Malignant insulinoma: Recommendations for characterisation and treatment Ann Endocrinol (Paris). 2013 Dec;74(5-6):523- 33.
• Nikfarjam, M., Warshaw, A.L., Axelrod, L.V et al. Improved contemporary surgical management of insulinomas: a 25-year experience at the Massachusetts General Hospital. Annals of Surgery, 2008 Jan;247(1):165-72.
• Shimizu S, Tanaka M, Konomi M, Mizumoto K, Yamaguchi K. Laparoscopic pancreatic surgery: Current indications and surgical results. Surgical Endoscopy And Other Interventional Techniques. March 2004, Volume 18, Issue 3, pp 402-6.
• Finlayson E, Clark OH. Surgical treatment of insulinomas. Surg Clin N Am. 2004;84:775-85.
• Roche A, Girish BV, de Baere T, Ducreux M, Elias D, Laplanche A, Boige V, Schlumberger M , Ruffle P. Prognostic factors for chemoembolization in liver metastasis from endocrine tumors. Hepato- gastroenterology 2004, 51(60):1751-56.
• Siperstein AE, Berber E. Cryoablation, Percutaneous Alcohol Injection, and Radiofrequency Ablation for Treatment of Neuroendocrine Liver Metastases. World Journal of Surgery. World J Surg. 2001 Jun;25(6):693-6.
• Van Schaik E, van Vliet EI, Feelders RA, Krenning EP, Khan S, Kamp K, Valkema R, van Nederveen FH, Teunissen JJ, Kwekkeboom DJ, de Herder WW. Improved control of severe hypoglycemia in patients with malignant insulinomas by peptide receptor radionuclide therapy. J Clin Endocrinol Metab. 2011 Nov;96(11):3381-9.
• Rougier P, Mitry E. Chemotherapy in the Treatment of Malignant Neuroendocrine 2000;62(suppl 1):73–8. Tu-mors. Digestion.
• Gill GV, Rauf O, MacFarlane IA. Diazoxide treatment for insulinoma: a national UK sur-vey Postgrad Med J. 1997 October; 73(864): 640–41.
• Vezzosi D, Bennet A, Rochaix P, Courbon F, Selves J, Pradere B, Buscail L, Susini C, Caron P. Octreotide in insulinoma patients: efficacy on hypoglycemia, relationships with Oc-treoscan scintigraphy and immunostaining with anti-sst2A and anti-sst5 antibodies. Eur J En-docrinol. 2005 May;152(5):757-67.
• Okabayashi T1, Shima Y, Sumiyoshi T, Kozuki A, Ito S, Ogawa Y, Kobayashi M, Hana-zaki K. Diagnosis and management of insulinoma.World J Gastroenterol. 2013 Feb 14;19(6):829-37.