Insulinoma Treatment & Management

  • Author: Zonera Ashraf Ali, MD; Chief Editor: Jules E Harris, MD   more...
 
Updated: Nov 23, 2011
 

Medical Care

Medical therapy is indicated in patients with malignant insulinomas and in those who will not or cannot undergo surgery. These measures are designed to prevent hypoglycemia and, in patients with malignant tumors, to reduce the tumor burden. In malignant insulinomas, dietary therapy with frequent oral feedings or enteral feedings may control mild symptoms of hypoglycemia. A trial of glucagon may be attempted to control hypoglycemia.

  • Diazoxide is related to the thiazide diuretics and reduces insulin secretion. Adverse effects include sodium retention, a tendency to congestive cardiac failure, and hirsutism.
  • Prescribe hydrochlorothiazide to counteract the edema and hyperkalemia secondary to diazoxide and to potentate its hyperglycemic effect.
  • Of patients with insulinoma, 50% may benefit from the somatostatin analogue octreotide to prevent hypoglycemia.[24]
    • The effect of the therapy depends on the presence of somatostatin receptor subtype 2 on insulinoma tumor cells.
    • As studies have shown, an OctreoScan is not a prerequisite before starting octreotide treatment. In patients with insulinoma and a negative scan finding, somatostatin decreased insulin levels significantly and lowered the incidence of hypoglycemic events.
  • CT-guided radiofrequency ablation has been used successfully to treat insulinoma in an elderly patient whose hypoglycemia that was refractory to diazoxide, and who was not a candidate for surgery because of comorbidities and poor physical condition.[25]
Next

Surgical Care

Because insulinoma resection achieves cure in 90% of patients, it is currently the therapy of choice.

  • Preoperative management
    • Administer diazoxide on the day of surgery in patients who respond to it. Diazoxide reduces the need for glucose supplements and the risk of hypoglycemia.
    • Monitor blood glucose level throughout surgery.
    • Infuse 10% dextrose in water at a rate of at least 100 mL/h.
    • A preoperative trial with diazoxide is indicated to determine whether the patient is a responder. (Five to 10% of patients do not respond.) This information helps determine the intraoperative strategy if the tumor is not localized.
    • In MEN 1, hypercalcemia must be corrected first by parathyroidectomy before insulinoma resection.[26]
  • Successful tumor location
    • Fully expose the pancreas, including a wide Kocher maneuver to allow complete bimanual palpation.
    • A large study from Spain showed laparoscopic surgery to be safe and effective in benign and malignant tumor resection. It led to a shorter hospital stay compared to open resection.[5]
    • Laparoscopic enucleation techniques, also in combination with preservation of the spleen for distal pancreatic tumors, have been described recently.[27]
    • Because of the small likelihood that a tumor that presents without metastatic spread is malignant, insulinomas may be removed by enucleation. Care should be taken to achieve total tumor capsule removal to prevent tumor recurrence. If enucleation is not possible, a larger pancreatic resection including pancreaticoduodenectomy may be necessary. This should only rarely be required. When metastatic insulinoma is found on a patient's initial presentation, the organ spread is to liver and sometimes to bone.
    • Avoid total pancreatectomy because of its high morbidity and mortality rates.
    • Major resections, such as the Whipple procedure, may become necessary when the tumor is found in the pancreatic head and local excision is not possible.
    • Resect all gross disease when multiple tumors or metastases are present.
    • If insulinoma is associated with MEN 1, the management strategy is modified because tumors are often multiple, diffusely spread in the pancreas, and of small size. Definite cure by surgery is rare.
    • Subtotal pancreatectomy with enucleation of tumors from the pancreatic head and uncinate processus often is recommended over simple enucleation because of frequent multiple tumors in MEN 1.
    • Intraoperative serum insulin measurements recently have been employed to ensure complete tumor removal. This may be important, particularly in patients with MEN 1 who harbor multiple insulinomas.
  • Tumor is found to be metastatic at surgery in about 5-10% of patients. It would be extremely uncommon for metastases to develop in a case in which only a solitary lesion was found on initial presentation.
    • If the patient is responsive to diazoxide, continue it, while more invasive imaging studies are performed before repetitive surgery is considered.
    • If the patient is not responsive (5-10%) or if drug intolerance is present and ectopic disease is excluded, a blind distal two-thirds pancreatectomy may be performed. (This procedure has only a 25% success rate.)
    • Most authorities recommend serial sectioning during resection.
    • Tumors that are not found at surgery normally are located in the pancreatic head (54%), body (20%), and tail (14%).
  • Metastatic disease found
    • Even when metastases are found, surgical excision is often feasible before any medical, chemotherapeutic, or other interventional therapy is considered.
    • Resect all gross disease, including wedge resections of hepatic metastases.
    • Avoid ligation of the hepatic artery in case further regional infusion therapy becomes necessary.
Previous
Next

Consultations

Consult with the anesthetist to plan for precise preoperative and intraoperative blood glucose monitoring. The approach should be multidisciplinary, with an endocrinologist, surgeon, and anesthesiologist.

Previous
Next

Diet

  • Because most tumors are not responsive to glucose, carbohydrate feedings every 2-3 hours can help maintain euglycemia, although obesity may develop.
  • Glucagon should be available for emergency use.
Previous
Next

Activity

Exercise may aggravate hypoglycemia in patients with insulinoma.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Zonera Ashraf Ali, MD  Consulting Staff, Main Line Oncology Hematology Associates, Lankenau Cancer Center

Zonera Ashraf Ali, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Klaus Radebold, MD, PhD  Research Associate, Department of Surgery, Yale University School of Medicine

Klaus Radebold, MD, PhD is a member of the following medical societies: American Gastroenterological Association and New York Academy of Sciences

Disclosure: Nothing to disclose.

Specialty Editor Board

Pradyumna D Phatak, MBBS, MD  Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD, is a member of the following medical societies: American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine; Consulting Staff, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

References

  1. Phan GQ, Yeo CJ, Hruban RH, et al. Surgical experience with pancreatic and peripancreatic neuroendocrine tumors: review of 125 patients. J Gastrointest Surg. Sep-Oct 1998;2(5):472-82. [Medline].

  2. Mathur A, Gorden P, Libutti SK. Insulinoma. Surg Clin North Am. Oct 2009;89(5):1105-21. [Medline].

  3. Dadan J, Wojskowicz P, Wojskowicz A. Neuroendocrine tumors of the pancreas. Wiad Lek. 2008;61(1-3):43-7. [Medline].

  4. Larijani B, Aghakhani S, Lor SS, Farzaneh Z, Pajouhi M, Bastanhagh MH. Insulinoma in Iran: a 20-year review. Ann Saudi Med. Nov-Dec 2005;25(6):477-80. [Medline].

  5. Fernandez-Cruz L, Blanco L, Cosa R, Rendon H. Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumors?. World J Surg. May 2008;32(5):904-17. [Medline].

  6. Dizon AM, Kowalyk S, Hoogwerf BJ. Neuroglycopenic and other symptoms in patients with insulinomas. Am J Med. Mar 1999;106(3):307-10. [Medline].

  7. Schmitt J, Boullu-Sanchis S, Moreau F, Drui S, Louis B, Chabrier G, et al. Association of malignant insulinoma and type 2 diabetes mellitus: a case report. Ann Endocrinol (Paris). Feb 2008;69(1):69-72. [Medline].

  8. Hrascan R, Pecina-Slaus N, Martic TN, Colic JF, Gall-Troselj K, Pavelic K. Analysis of selected genes in neuroendocrine tumours: insulinomas and phaeochromocytomas. J Neuroendocrinol. Aug 2008;20(8):1015-22. [Medline].

  9. Waickus CM, de Bustros A, Shakil A. Recognizing factitious hypoglycemia in the family practice setting. J Am Board Fam Pract. Mar-Apr 1999;12(2):133-6. [Medline].

  10. Redmon JB, Nuttall FQ. Autoimmune hypoglycemia. Endocrinol Metab Clin North Am. Sep 1999;28(3):603-18, vii. [Medline].

  11. Eriguchi N, Aoyagi S, Hara M, et al. Nesidioblastosis with hyperinsulinemic hypoglycemia in adults: report of two cases. Surg Today. 1999;29(4):361-3. [Medline].

  12. Starke A, Saddig C, Kirch B, Tschahargane C, Goretzki P. Islet hyperplasia in adults: challenge to preoperatively diagnose non-insulinoma pancreatogenic hypoglycemia syndrome. World J Surg. May 2006;30(5):670-9. [Medline].

  13. Wiesli P, Uthoff H, Perren A, et al. Are biochemical markers of neuroendocrine tumors coreleased with insulin following local calcium stimulation in patients with insulinomas?. Pancreas. Oct 2011;40(7):995-9. [Medline].

  14. van Bon AC, Benhadi N, Endert E, Fliers E, Wiersinga WM. Evaluation of endocrine tests. D: the prolonged fasting test for insulinoma. Neth J Med. Jul-Aug 2009;67(7):274-8. [Medline].

  15. Boukhman MP, Karam JM, Shaver J, et al. Localization of insulinomas. Arch Surg. Aug 1999;134(8):818-22; discussion 822-3. [Medline].

  16. Hashimoto LA, Walsh RM. Preoperative localization of insulinomas is not necessary. J Am Coll Surg. Oct 1999;189(4):368-73. [Medline].

  17. Liu Y, Song Q, Jin HT, Lin XZ, Chen KM. The value of multidetector-row CT in the preoperative detection of pancreatic insulinomas. Radiol Med. Sep 30 2009;[Medline].

  18. Anaye A, Mathieu A, Closset J, Bali MA, Metens T, Matos C. Successful preoperative localization of a small pancreatic insulinoma by diffusion-weighted MRI. JOP. Sep 4 2009;10(5):528-31. [Medline].

  19. Kirkeby H, Vilmann P, Burcharth F. Insulinoma diagnosed by endoscopic ultrasonography-guided biopsy. J Laparoendosc Adv Surg Tech A. Jun 1999;9(3):295-8. [Medline].

  20. Proye C, Malvaux P, Pattou F, et al. Noninvasive imaging of insulinomas and gastrinomas with endoscopic ultrasonography and somatostatin receptor scintigraphy. Surgery. Dec 1998;124(6):1134-43; discussion 1143-4. [Medline].

  21. McLean A. Endoscopic ultrasound in the detection of pancreatic islet cell tumours. Cancer Imaging. Mar 29 2004;4(2):84-91. [Medline].

  22. 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. Oct 9 2009;[Medline].

  23. Wild D, Christ E, Caplin ME, et al. Glucagon-like peptide-1 versus somatostatin receptor targeting reveals 2 distinct forms of malignant insulinomas. J Nucl Med. Jul 2011;52(7):1073-8. [Medline].

  24. Arnold R, Simon B, Wied M. Treatment of neuroendocrine GEP tumours with somatostatin analogues: a review. Digestion. 2000;62 Suppl 1:84-91. [Medline].

  25. Limmer S, Huppert PE, Juette V, Lenhart A, Welte M, Wietholtz H. Radiofrequency ablation of solitary pancreatic insulinoma in a patient with episodes of severe hypoglycemia. Eur J Gastroenterol Hepatol. Sep 2009;21(9):1097-101. [Medline].

  26. Lo CY, Lam KY, Fan ST. Surgical strategy for insulinomas in multiple endocrine neoplasia type I. Am J Surg. Apr 1998;175(4):305-7. [Medline].

  27. Dexter SP, Martin IG, Leindler L, et al. Laparoscopic enucleation of a solitary pancreatic insulinoma. Surg Endosc. Apr 1999;13(4):406-8. [Medline].

  28. Moscetti L, Saltarelli R, Giuliani R, et al. Intra-arterial liver chemotherapy and hormone therapy in malignant insulinoma: case report and review of the literature. Tumori. Nov-Dec 2000;86(6):475-9. [Medline].

  29. Smith MC, Liu J, Chen T, et al. OctreoTher: ongoing early clinical development of a somatostatin- receptor-targeted radionuclide antineoplastic therapy. Digestion. 2000;62 Suppl 1:69-72. [Medline].

  30. Bourcier ME, Sherrod A, DiGuardo M, Vinik AI. Successful control of intractable hypoglycemia using rapamycin in an 86-year-old man with a pancreatic insulin-secreting islet cell tumor and metastases. J Clin Endocrinol Metab. Sep 2009;94(9):3157-62. [Medline].

  31. Gonzalez-Gonzalez A, Recio-Cordova JM. Liver metastases 9 years after removal of a malignant insulinoma which was initially considered benign. JOP. 2006;7(2):226-9. [Full Text].

  32. Abboud B, Boujaoude J. Occult sporadic insulinoma: localization and surgical strategy. World J Gastroenterol. Feb 7 2008;14(5):657-65. [Medline].

  33. Ahlman H, Wangberg B, Jansson S, et al. Interventional treatment of gastrointestinal neuroendocrine tumours. Digestion. 2000;62 Suppl 1:59-68. [Medline].

  34. Begu-Le Corroller A, Valero R, Moutardier V, Henry JF, Le Treut YP, Gueydan M. Aggressive multimodal therapy of sporadic malignant insulinoma can improve survival: A retrospective 35-year study of 12 patients. Diabetes Metab. Jun 13 2008;[Medline].

  35. Diagnosis and management of pancreatic endocrine tumors. In: De Vita V, Lawrence T, Rosenberg S. Cancer. Principles and Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott, Williams and Wilkins; 2008:1706-15.

  36. Faggiano A, Mansueto G, Ferolla P, Milone F, del Basso de Caro ML, Lombardi G, et al. Diagnostic and prognostic implications of the World Health Organization classification of neuroendocrine tumors. J Endocrinol Invest. Mar 2008;31(3):216-23. [Medline].

  37. Grant CS. Surgical aspects of hyperinsulinemic hypoglycemia. Endocrinol Metab Clin North Am. Sep 1999;28(3):533-54. [Medline].

  38. Jensen RT. Pancreatic endocrine tumors: recent advances. Ann Oncol. 1999;10 Suppl 4:170-6. [Medline].

  39. Keymeulen B, Bossuyt A, Peeters TL, Somers G. 111In-octreotide scintigraphy: a tool to select patients with endocrine pancreatic tumors for octreotide treatment?. Ann Nucl Med. Aug 1995;9(3):149-52. [Medline].

  40. Kuzin NM, Egorov AV, Kondrashin SA, et al. Preoperative and intraoperative topographic diagnosis of insulinomas. World J Surg. Jun 1998;22(6):593-7; discussion 597-8. [Medline].

  41. Le Roith D. Tumor-induced hypoglycemia. N Engl J Med. Sep 2 1999;341(10):757-8. [Medline].

  42. Molven A, Matre GE, Duran M, Wanders RJ, Rishaug U, Njolstad PR. Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. Diabetes. Jan 2004;53(1):221-7. [Medline].

  43. Rougier P, Mitry E. Chemotherapy in the treatment of neuroendocrine malignant tumors. Digestion. 2000;62 Suppl 1:73-8. [Medline].

  44. Ruszniewski P, Malka D. Hepatic arterial chemoembolization in the management of advanced digestive endocrine tumors. Digestion. 2000;62 Suppl 1:79-83. [Medline].

 
Previous
Next
 
CT scan image with oral and intravenous contrast in a patient with biochemical evidence of insulinoma. The 3-cm contrast-enhancing neoplasm (arrow) is seen in the tail of the pancreas (P) posterior to the stomach (S) (Yeo, 1993).
Endoscopic ultrasonography in a patient with an insulinoma. The hypoechoic neoplasm (arrows) is seen in the body of the pancreas anterior to the splenic vein (SV) (Rosch, 1992).
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.