eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs

Insulinoma: Follow-up

Author: Zonera Ashraf Ali, MD, Consulting Staff, Main Line Oncology Hematology Associates, Lankenau Cancer Center
Coauthor(s): Klaus Radebold, MD, PhD, Research Associate, Department of Surgery, Yale University School of Medicine
Contributor Information and Disclosures

Updated: Nov 3, 2009

Follow-up

Further Inpatient Care

  • After insulinoma resection, hyperglycemia may persist for 48-72 hours because of chronic down-regulation of insulin-receptors by the following:
    • Previously high circulating insulin levels secreted by the tumor
    • Suppression of normal pancreatic B cells
  • Small subcutaneous doses of insulin every 3-6 hours may be necessary if plasma glucose level exceeds 300 mg/dL (16.7 mmol/L).
  • Patients with major pancreatic resections may develop diabetes mellitus.
  • Streptozocin chemotherapy may be used for cytotoxic drug control of systemic disease. This chemotherapeutic agent appears to be toxic to cells producing insulin. Short-acting somatostatin analogues may be tried to control insulin release. In patients with unresectable metastatic disease to the liver, when systemic chemotherapy was unsuccessful, embolization of the hepatic artery and intraarterial chemotherapy may be indicated to control symptoms and hormone release, to inhibit tumor growth, and to improve survival.26
  • For insulinomas, some cases of sustained improvement in hypoglycemic attacks have been reported, particularly when streptozotocin has been used.
  • New therapy is currently under investigation.
    • OctreoTher consists of a somatostatin peptide analogue, labeled with a beta-emitter (yttrium-90). By targeting somatostatin-receptor–positive tumors (imaged by scan), it may deliver a local tumoricidal dose of radiation.27
    • OctreoTher binds to somatostatin receptor 2 and 3, has a mean path length of 5 mm, and a physical half-life of 64.1 hours.

Inpatient & Outpatient Medications

  • Continue diazoxide and hydrochlorothiazide in patients who are not fit for surgery or when tumor resection was unsuccessful.

Transfer

  • In advanced metastatic disease, the indications for chemotherapy or other interventional treatments must be emphasized in a multidisciplinary way and discussed with surgeons, specialists in chemoembolization, gastroenterologists, endocrinologists, and medical oncologists.

Complications

  • Surgical complications (eg, pancreatic leakage) occur in about 14% of patients.
  • Pseudocysts
  • Other complications
  • Permanent diabetes mellitus may occur in about 5% of patients, mainly in those with major pancreatic resections.

Prognosis

  • Approximately 90-95% of insulinomas are benign. Long-term cure with complete resolution of preoperative symptoms is expected after complete resection.
  • Recurrence of benign insulinomas was observed in 5.4% of patients in a series of 120 patients over a period of 4-17 years. The same diagnostic and therapeutic approach was recommended, including surgical exploration and tumor resection.
  • Indications for chemotherapy include progressive disease with an increase of greater than 25% of the main tumor masses in a follow-up period of 12 months, or tumor symptoms not treatable with other methods. Polychemotherapies have achieved better results than monochemotherapies.
    • The current medical treatment is based primarily on streptozotocin in combination with doxorubicin or 5-fluorouracil. Streptozotocin alone may achieve partial response in 50% of patients and complete response in 20%. The median survival in one study was 16 months.
    • If streptozotocin is combined with 5-fluorouracil, 33% of patients show complete response, with the median survival increasing to 26 months.
    • There is a single case report of successful control of intractable hypoglycemia in an elderly man with metastatic insulinoma through the use of oral rapamycin (sirolimus), 2 mg/d.28
    • Patients may develop nonfunctioning metastatic disease to the liver up to 14 years after insulinoma resection.29 Note that some insulinomas are indolent (depending on the tumor biology), resulting in prolonged survival.

Miscellaneous

Medicolegal Pitfalls

  • Monitor blood glucose levels carefully during surgery, especially when the insulinoma is being palpated and manipulated.
  • Exclude factitious hypoglycemia before surgery, particularly in patients from the medical profession.
  • Screen for MEN 1. When results are positive, the hypercalcemia must be corrected before abdominal surgery is performed.

Special Concerns

  • In patients with insulinoma and MEN 1 syndrome, family members must be screened for the syndrome.
  • A genetic test has not been developed yet but may be available in the near future.
 


More on Insulinoma

Overview: Insulinoma
Differential Diagnoses & Workup: Insulinoma
Treatment & Medication: Insulinoma
Follow-up: Insulinoma
Multimedia: Insulinoma
References
[ CLOSE WINDOW ]

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. 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].

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

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

  16. 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].

  17. 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].

  18. 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].

  19. 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].

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

  21. 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].

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

  23. 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].

  24. 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].

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

  26. 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].

  27. 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].

  28. 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].

  29. 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].

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

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

  32. 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].

  33. 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.

  34. 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].

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

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

  37. 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].

  38. 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].

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

  40. 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].

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

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

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

insulinoma, hyperinsulinism, endogenous hyperinsulinism, islet cell adenoma, pancreatic islet cell, neuroendocrine tumor, hypoglycemia, B-cell tumor of the pancreas, adenoma of the islets of Langerhans

[ CLOSE WINDOW ]

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.

Medical Editor

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

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

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 at Tucson; 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; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
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.