World Journal of Endocrine Surgery

Register      Login

VOLUME 1 , ISSUE 1 ( September-December, 2009 ) > List of Articles

RESEARCH ARTICLE

When No Tumor can be Found in Patients with the Diagnosis of Pancreatic Hyperinsulinism Unsuccessful Operation or a Noninsulinoma Pancreatic Hypoglycemia Syndromes (NIPHS): Personal Experience in 20 of 125 Patients

Shun Yu Chi, Achim Starke, Bernhard Lammers, Fong Fu Chou, Peter Goretzki

Citation Information : Chi SY, Starke A, Lammers B, Chou FF, Goretzki P. When No Tumor can be Found in Patients with the Diagnosis of Pancreatic Hyperinsulinism Unsuccessful Operation or a Noninsulinoma Pancreatic Hypoglycemia Syndromes (NIPHS): Personal Experience in 20 of 125 Patients. World J Endoc Surg 2009; 1 (1):31-38.

DOI: 10.5005/jp-journals-10002-1007

Published Online: 01-12-2009

Copyright Statement:  Copyright © 2009; Jaypee Brothers Medical Publishers (P) Ltd.


Abstract

Background

With combination of intraoperative ultrasound and palpation, more than 90-95% of all insulinomas will be found during exploration. But even in experienced hands some are not detected. When a familial multiple endocrine neoplasia type 1 (MEN-1) has been excluded, the question arises intraoperatively, whether we just failed to find an insulinoma or whether another illness is causing the disease. The latter may be a noninsulinoma pancreatic hypoglycemia caused by focal hyperplastic of islets or by neoplastic isleta with or without microadenomas (synonymous: “adult nesidioblastosis” or “insulinomatosis” by pathologists and “NIPHS” by clinicians).

Our own experience with 20 out of 125 patients with pancreatic hyperinsulinism is demonstrated, where we did not find an insulinoma intraoperatively. In some of them operative flaws led to this result and in the majority preoperative diagnosis of NIPHS was confirmed. Thus NIPHS accounts for 16% of all forms of sporadic pancreatic hyperinsulinism and has to be integrated into our daily preoperative work-up and intraoperative management.

Patients and methods

The charts of 125 adult patients with documented endogenous hyperinsulinemic hypoglycemia were extracted, operated on between 1986 and 2008. All patients with benign or malignant solid insulinoma and all patients with familial MEN-1 were excluded, leaving 20 patients (xx%) with sporadic disease, in whom no insulinoma was detected during exploration. These were 4 men and 16 women with a mean age of 45.4 ± 14.8 years (range 18 to 76 years).

Results

Eleven patients underwent operation for a presumed insulinoma, of which the final diagnoses were insulinoma in 4 (three at the head and one at the tail of pancreas) and NIPHS in 7, respectively. The other 9 patients underwent operation for preoperatively diagnosed NIPHS and were all proven to have NIPHS, postoperatively. Patients with insulinoma were all cured by removal of their tumors. The 11 patients with NIPHS were treated by a partial or subtotal pancreatectomy and none had reported further episodes of neuroglycopenia after 77 months of follow-up. Three of them developed postoperative insulin-dependent diabetes mellitus.

Conclusion

When a circumscribed insulinoma cannot be detected by preoperative localization studies in patients with proven endogenous hyperinsulinimic hypoglycemia the biochemical results of oral glucose tolerance test (OGTT) and 72 hours fast should be reassessed, carefully. When the data clearly point to an insulinoma, a thorough surgical examination undertaken, with special focus of attention on the head and uncinate process of the pancreas. If still no tumor is found, the operation should be terminated. When results of OGTT and 72 hours fast assume NIPHS a selective arterial calcium stimulation test is indicated, since the necessary 70-80% pancreatectomy can be guided by results of the stimulated insulin gradient. Following these principles all 20 patients were cured in a mean follow-up of 7.5 years. In 2 patients (10%), however, extensive partial pancreatectomy resulted in a mild insulin dependent diabetes mellitus.

Altogether sixteen out of 20 patients (%) with sporadic endogenous pancreatic hyperinsulinemia and failed demonstration of a single tumor proved to have NIPHS. Even when an insulinoma is suspected after biochemical analysis and preoperative localization study as well as intraoperative findings failed to show a tumor (n = 11) 7 patients (%) demonstrated to have NIPHS.


PDF Share
  1. Surgical aspects of hyperinsulinemic hypoglycemia. Endocrinol Metab Clin North Am Sep 1999;28(3):533-54.
  2. Noninsulinoma pancreatogenous hypoglycemia: A novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir 6.2 and SUR1 genes. J Clin Endocrinol Metab 1999;84:1582-89.
  3. Therapeutic experience of 65 cases with organic hyperinsulinism. Langenbecks Arch Chir 2000;385:329-36.
  4. Occult functioning insulinomas: Which localizing studies are indicated? Surgery 1992;112:1010-14.
  5. Islet hyperplasia in adults: Challenge to preoperatively diagnose noninsulinoma pancreatogenic hypoglycemia syndrome. World J Surg 2006;30:670-79.
  6. Nesidioblastosis: An old term and a new understanding. World J Surg 2004;28:1227-30.
  7. Intra-arterial calcium stimulation test for detection of insulinomas. World J Surg 1993;17:439-43.
  8. Noninsulinoma pancreatogenous hypoglycemia syndrome: An update in 10 surgically treated patients. Surgery 2000;128:937-45.
  9. Nesidioblastosis associated with hyperinsulinemic hypoglycemia in adults: Review of the literature. Eur J Intern Med 2004;15:407-10.
  10. Persistent hyperinsulinemic hypoglycemia in 15 adults with diffuse nesidioblastosis. Am J Surg Pathol 2005;29:524-33.
  11. Noninsulinoma pancreatogenous hypoglycemia syndrome: A rare case of adult-onset nesidioblastosis. Intern Med 2005;44:843-47.
  12. Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium. Ann Intern Med 1995;123:269-73.
  13. Adult-onset nesidioblastosis causing hypoglycemia: An important clinical entity and continuing treatment dilemma. Arch Surg 2001;136:656-63.
  14. Nesidioblastosis in adults: A challenging cause of organic hyperinsulinism. Eur J Clin Invest 2003;33:488-92.
  15. Surgical treatment and outcome in insulinoma. Zentralbl Chir 2001;126:273-78.
  16. Blind distal pancreatectomy for occult insulinoma, an inadvisable procedure. J Am Coll Surg 2002;194:761-64.
  17. Occult insulinoma. Br J Surg 2000;87:385-87.
  18. The management of insulinoma. Br J Surg 2006;93:264-75.
  19. Clinical features and morphological characterization of 10 patients with noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS). Clin Endocrinol 2006;65:566-78.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.