Case Report | | Peer-Reviewed

Modified Frey Technique for Treatment of Persistent Hyperinsulinemic Hyperglycemia Due to Nesidioblastosis: A Case Report

Received: 14 March 2025     Accepted: 14 April 2025     Published: 29 May 2025
Views:       Downloads:
Abstract

Introduction: Hypoglycemia in non-diabetic individuals is rare but represents a significant diagnostic and therapeutic challenge. One of its uncommon causes is Nesidioblastosis, characterized by diffuse or focal hyperplasia of pancreatic β cells, leading to endogenous hyperinsulinemic hypoglycemia. Although more frequent in neonates, cases in adults have been increasingly recognized, especially in the absence of insulinoma. In adults, this condition presents with β cell hypertrophy, enlarged islets, and hyperchromatic nuclei, with postprandial hypoglycemia being its main symptom. This article aims to demonstrate a technical modification for preserving the duodenum and bile duct in the treatment of a patient with Nesidioblastosis who underwent several surgical treatments without results. Case Presentation: This article reports the case of a man with intermittent symptomatic hypoglycemia for two years, who required multiple surgical interventions for effective control of the disease. Was done a technical modification for preserving the duodenum and bile duct in the treatment of a patient with Nesidioblastosis who underwent several surgical treatments without results. Given the current clinical picture, in which a pancreaticoduodenectomy with total resection of the remaining pancreas would be indicated due to hypoglycemia refractory to several types of clinical and surgical treatments, we decided to perform the Frey technique for this case, thus preserving a small segment of the pancreas together with the duodenal arch and thus preserving the main bile duct. Discussion and Conclusion: Preoperative diagnosis is challenging due to the nonspecificity of symptoms and the absence of specific functional tests and is usually confirmed by histopathological examination after surgery. Initial treatment involves nutritional modifications and the use of medications. However, moderate to severe and refractory cases require surgical intervention. Partial or subtotal pancreatectomy is effective, although some cases require multiple surgeries. In the reported case, the Frey technique was successfully used, promoting effective glycemic control and minimizing gastrointestinal complications. Despite partial preservation of the pancreas, the patient developed postoperative diabetes, highlighting the importance of balancing effective removal of hyperfunctioning tissue and preservation of pancreatic function. It is concluded that surgical treatment as a last resort and using the technique described by Frey as a way to preserve the gastrointestinal tract and avoid total pancreatectomy with its serious repercussions on the patient's metabolism.

Published in Journal of Surgery (Volume 13, Issue 3)
DOI 10.11648/j.js.20251303.11
Page(s) 45-50
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Frey Technique, Nesidioblastosis, Insulin, Hypoglycemia

References
[1] De Leon DD, Arnoux JB, Banerjee I, Bergada I, Bhatti T, Conwell LS, et al. International guidelines for the diagnosis and management of hyperinsulinism. Horm Res Paediatr. 2024; 97(3): 279–98.
[2] Sempoux C, Guiot Y, Jaubert F, Rahier J. Focal and diffuse forms of congenital hyperinsulinism: The keys for differential diagnosis. Endocr Pathol. 2004; 15(3): 241–6.
[3] Heitz PU, Klöppel G, Häcki WH, Polak JM, Pearse AGE. Nesidioblastosis: The pathologic basis of persistent hyperinsulinemic hypoglycemia in infants: Morphologic and quantitative analysis of seven cases based on specific immunostaining and electron microscopy. Diabetes. 1977; 26(7): 632–42.
[4] Goossens A, Gepts W, Saudubray JM, Bonnefont JP, Nihoul-Fekete, Heitz PU, et al. Diffuse and focal nesidioblastosis. A clinicopathological study of 24 patients with persistent neonatal hyperinsulinemic hypoglycemia. Am J Surg Pathol. 1989; 13(9): 766–75.
[5] DeLellis RA et al. World Health Organization classification of tumours: Pathology and genetics of tumours of endocrine organs. IARC Press. Lyon, 2004.
[6] Fajans SS, Floyd JC Jr. Fasting hypoglycemia in adults. N Engl J Med. 1976; 294(14): 766–72.
[7] Klöppel G, Willemer S, Stamm B, Häcki WH, Heitz PU. Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I. An immunocytochemical study of nine patients. Cancer. 1986; 57(9): 1824–32.
[8] Reinecke-Lüthge A, Koschoreck F, Klöppel G. The molecular basis of persistent hyperinsulinemic hypoglycemia of infancy and its pathologic substrates. Virchows Arch. 2000; 436(1): 1–5.
[9] Thompson GB, F. John Service, Andrews JC, Lloyd RV, Natt N, van Heerden JA, et al. Noninsulinoma pancreatogenous hypoglycemia syndrome: An update in 10 surgically treated patients. Surgery. 2000; 128(6): 937–45.
[10] Anlauf M, Wieben D, Perren A, Sipos B, Komminoth P, Raffel A, et al. Persistent hyperinsulinemic hypoglycemia in 15 adults with diffuse nesidioblastosis: diagnostic criteria, incidence, and characterization of beta-cell changes. Am J Surg Pathol. 2005; 29(4): 524–33.
[11] García-Santos EP, Manzanares-Campillo M del C, Padilla-Valverde D, Villarejo-Campos P, Gil-Rendo A, Muñoz-Atienza V, et al. Nesidioblastosis. A case of hyperplasia of the islets of Langerhans in the adult. Pancreatology. 2013; 13(5): 544–8.
[12] F. John Service, Natt N, Thompson GB, Grant CS, van Heerden JA, Andrews JC, et al. Noninsulinoma pancreatogenous hypoglycemia: A novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes1. J Clin Endocrinol Metab. 1999; 84(5): 1582–9.
[13] Witteles RM. Adult-onset nesidioblastosis causing hypoglycemia: An important clinical entity and continuing treatment dilemma. Arch Surg. 2001; 136(6): 656.
[14] Sandler R, Horwitz DL, Rubenstein AH, Kuzuya H. Hypoglycemia and endogenous hyperinsulinism complicating diabetes mellitus. Am J Med. 1975; 59(5): 730–6.
[15] Stefanini P, Carboni M, Patrassi N, Basoli A. Beta-islet cell tumors of the pancreas: results of a study on 1,067 cases. Surgery. 1974 Apr; 75(4): 597-609. PMID: 4366135.
[16] Klöppel G, Anlauf M, Raffel A, Perren A, Knoefel WT. Adult diffuse nesidioblastosis: genetically or environmentally induced? Hum Pathol. 2008; 39(1): 3–8.
[17] Raffel A, Krausch M M, 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(2): 179–84.
[18] Clancy TE, Moore FD Jr, Zinner MJ. Post-gastric bypass hyperinsulinism with nesidioblastosis: subtotal or total pancreatectomy may be needed to prevent recurrent hypoglycemia. J Gastrointest Surg. 2006; 10(8): 1116–9.
[19] Frey CF, Suzuki M, Isaji S, Zhu Y. Pancreatic resection for chronic pancreatitis. Surg Clin North Am. 1989; 69(3): 499–528.
[20] Thapa S, Kaur K, Yadav GK, Kumari D, Phulware RH. Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)/Nesidioblastosis as the underlying cause of recurrent hypoglycemia in a diabetic adult. Autops Case Rep. 2023; 13: e2023451.
[21] Dieterle MP, Husari A, Prozmann SN, Wiethoff H, Stenzinger A, Röhrich M, et al. An uncommon cause of recurrent presyncope, dizziness, and tachycardia: A case report of diffuse, adult-onset nesidioblastosis/non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Biomedicines. 2023; 11(6).
[22] Cao J, Kim C, Huynh T, Frugoli A, Henson H, Valdez V, et al. BYPASS-OMA: Hypoglycemic hyperinsulinemic nesidioblastosis after gastric bypass surgery-A case report and review of the literature. Case Rep Endocrinol. 2022; 2022: 5472304.
Cite This Article
  • APA Style

    Lisboa, F. F., Junior, F. F. L., Ferreira, L. F. N., Dantas, G. D. C., Cruz, G. C. D. O. (2025). Modified Frey Technique for Treatment of Persistent Hyperinsulinemic Hyperglycemia Due to Nesidioblastosis: A Case Report. Journal of Surgery, 13(3), 45-50. https://doi.org/10.11648/j.js.20251303.11

    Copy | Download

    ACS Style

    Lisboa, F. F.; Junior, F. F. L.; Ferreira, L. F. N.; Dantas, G. D. C.; Cruz, G. C. D. O. Modified Frey Technique for Treatment of Persistent Hyperinsulinemic Hyperglycemia Due to Nesidioblastosis: A Case Report. J. Surg. 2025, 13(3), 45-50. doi: 10.11648/j.js.20251303.11

    Copy | Download

    AMA Style

    Lisboa FF, Junior FFL, Ferreira LFN, Dantas GDC, Cruz GCDO. Modified Frey Technique for Treatment of Persistent Hyperinsulinemic Hyperglycemia Due to Nesidioblastosis: A Case Report. J Surg. 2025;13(3):45-50. doi: 10.11648/j.js.20251303.11

    Copy | Download

  • @article{10.11648/j.js.20251303.11,
      author = {Fernando Freire Lisboa and Fernando Freire Lisboa Junior and Luis Fernando Nunes Ferreira and Gabriel Diniz Câmara Dantas and Gabriel Carvalho de Oliveira Cruz},
      title = {Modified Frey Technique for Treatment of Persistent Hyperinsulinemic Hyperglycemia Due to Nesidioblastosis: A Case Report
    },
      journal = {Journal of Surgery},
      volume = {13},
      number = {3},
      pages = {45-50},
      doi = {10.11648/j.js.20251303.11},
      url = {https://doi.org/10.11648/j.js.20251303.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.js.20251303.11},
      abstract = {Introduction: Hypoglycemia in non-diabetic individuals is rare but represents a significant diagnostic and therapeutic challenge. One of its uncommon causes is Nesidioblastosis, characterized by diffuse or focal hyperplasia of pancreatic β cells, leading to endogenous hyperinsulinemic hypoglycemia. Although more frequent in neonates, cases in adults have been increasingly recognized, especially in the absence of insulinoma. In adults, this condition presents with β cell hypertrophy, enlarged islets, and hyperchromatic nuclei, with postprandial hypoglycemia being its main symptom. This article aims to demonstrate a technical modification for preserving the duodenum and bile duct in the treatment of a patient with Nesidioblastosis who underwent several surgical treatments without results. Case Presentation: This article reports the case of a man with intermittent symptomatic hypoglycemia for two years, who required multiple surgical interventions for effective control of the disease. Was done a technical modification for preserving the duodenum and bile duct in the treatment of a patient with Nesidioblastosis who underwent several surgical treatments without results. Given the current clinical picture, in which a pancreaticoduodenectomy with total resection of the remaining pancreas would be indicated due to hypoglycemia refractory to several types of clinical and surgical treatments, we decided to perform the Frey technique for this case, thus preserving a small segment of the pancreas together with the duodenal arch and thus preserving the main bile duct. Discussion and Conclusion: Preoperative diagnosis is challenging due to the nonspecificity of symptoms and the absence of specific functional tests and is usually confirmed by histopathological examination after surgery. Initial treatment involves nutritional modifications and the use of medications. However, moderate to severe and refractory cases require surgical intervention. Partial or subtotal pancreatectomy is effective, although some cases require multiple surgeries. In the reported case, the Frey technique was successfully used, promoting effective glycemic control and minimizing gastrointestinal complications. Despite partial preservation of the pancreas, the patient developed postoperative diabetes, highlighting the importance of balancing effective removal of hyperfunctioning tissue and preservation of pancreatic function. It is concluded that surgical treatment as a last resort and using the technique described by Frey as a way to preserve the gastrointestinal tract and avoid total pancreatectomy with its serious repercussions on the patient's metabolism.
    },
     year = {2025}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Modified Frey Technique for Treatment of Persistent Hyperinsulinemic Hyperglycemia Due to Nesidioblastosis: A Case Report
    
    AU  - Fernando Freire Lisboa
    AU  - Fernando Freire Lisboa Junior
    AU  - Luis Fernando Nunes Ferreira
    AU  - Gabriel Diniz Câmara Dantas
    AU  - Gabriel Carvalho de Oliveira Cruz
    Y1  - 2025/05/29
    PY  - 2025
    N1  - https://doi.org/10.11648/j.js.20251303.11
    DO  - 10.11648/j.js.20251303.11
    T2  - Journal of Surgery
    JF  - Journal of Surgery
    JO  - Journal of Surgery
    SP  - 45
    EP  - 50
    PB  - Science Publishing Group
    SN  - 2330-0930
    UR  - https://doi.org/10.11648/j.js.20251303.11
    AB  - Introduction: Hypoglycemia in non-diabetic individuals is rare but represents a significant diagnostic and therapeutic challenge. One of its uncommon causes is Nesidioblastosis, characterized by diffuse or focal hyperplasia of pancreatic β cells, leading to endogenous hyperinsulinemic hypoglycemia. Although more frequent in neonates, cases in adults have been increasingly recognized, especially in the absence of insulinoma. In adults, this condition presents with β cell hypertrophy, enlarged islets, and hyperchromatic nuclei, with postprandial hypoglycemia being its main symptom. This article aims to demonstrate a technical modification for preserving the duodenum and bile duct in the treatment of a patient with Nesidioblastosis who underwent several surgical treatments without results. Case Presentation: This article reports the case of a man with intermittent symptomatic hypoglycemia for two years, who required multiple surgical interventions for effective control of the disease. Was done a technical modification for preserving the duodenum and bile duct in the treatment of a patient with Nesidioblastosis who underwent several surgical treatments without results. Given the current clinical picture, in which a pancreaticoduodenectomy with total resection of the remaining pancreas would be indicated due to hypoglycemia refractory to several types of clinical and surgical treatments, we decided to perform the Frey technique for this case, thus preserving a small segment of the pancreas together with the duodenal arch and thus preserving the main bile duct. Discussion and Conclusion: Preoperative diagnosis is challenging due to the nonspecificity of symptoms and the absence of specific functional tests and is usually confirmed by histopathological examination after surgery. Initial treatment involves nutritional modifications and the use of medications. However, moderate to severe and refractory cases require surgical intervention. Partial or subtotal pancreatectomy is effective, although some cases require multiple surgeries. In the reported case, the Frey technique was successfully used, promoting effective glycemic control and minimizing gastrointestinal complications. Despite partial preservation of the pancreas, the patient developed postoperative diabetes, highlighting the importance of balancing effective removal of hyperfunctioning tissue and preservation of pancreatic function. It is concluded that surgical treatment as a last resort and using the technique described by Frey as a way to preserve the gastrointestinal tract and avoid total pancreatectomy with its serious repercussions on the patient's metabolism.
    
    VL  - 13
    IS  - 3
    ER  - 

    Copy | Download

Author Information
  • Sections