Download PDF
Horm Metab Res
DOI: 10.1055/a-2620-2931
Original Article: Endocrine Care

Outcomes of 68Ga-NODAGA-Exendin-4 PET/CT Guided Surgical Management of Insulinomas in MEN1: A Preliminary Study

Ketki Sunil Ambulkar‡
1   Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)
,
Ravikumar Shah‡
2   Harikrushna Hormone Clinic, Anand, India
,
Anurag Lila
1   Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)
,
Anima Sharma
1   Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)
,
Rohit Barnabas
1   Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)
,
Manjiri Karlekar
1   Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)
,
Saba Samad Memon
1   Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)
,
Vijaya Sarathi
3   Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, India (Ringgold ID: RIN29549)
,
Sameer Rege
4   Department of General Surgery, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)
,
Priyanka Verma
5   Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India (Ringgold ID: RIN75893)
,
Gaurav Malhotra
5   Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India (Ringgold ID: RIN75893)
,
Vikram Lele
6   Department of Nuclear Medicine, Jaslok Hospital & Research Center, Mumbai, India (Ringgold ID: RIN29445)
,
Tushar Bandgar 
1   Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

The data on the use of 68Ga-NODAGA-exendin-4 PET/CT in localizing multiple endocrine neoplasia type 1 (MEN1)-related insulinomas is evolving; however, surgical outcomes data are not available. We describe our cohort of patients with MEN1-related endogenous hyperinsulinemic hypoglycemia (EHH), where 68Ga-NODAGA-exendin-4 PET/CT was used to guide conservative surgery. A retrospective record review of MEN1-related EHH cases managed between 2000 and 2024 was performed for clinical features, imaging, and management. Outcomes were assessed for patients whose surgical extent was determined by 68Ga-NODAGA-exendin-4 PET/CT versus conventional imaging (CECT and 68Ga-DOTATATE PET/CT). Five patients with a median age of 17 (15.5–18.5 years) with EHH underwent laparoscopic, single lesion enucleation based on 68Ga-NODAGA-exendin-4 PET/CT. On preoperative imaging, CT identified culprit lesion in four, while 68Ga-DOTATATE PET/CT localized in one, and had one false positive uptake in non-functioning NET. The median duration of hospital stay was 6 (5.5–9) days. Over a median follow-up of 48 (3.5–84.5) months, none had EHH recurrence or exocrine/endocrine pancreatic insufficiency. On follow-up, one patient had an uneventful pregnancy and delivery. In the remaining 15, who underwent surgery based on conventional imaging, 12 (80%) required extensive surgery beyond enucleation, of which two needed intraoperative ultrasound localization. This group had a postoperative hospital stay of 11 (8–23) days, one recurrence after 84 months, and pancreatic insufficiency in 5 (33%). Our center observation suggests that GLP1R-based PET/CT-guided conservative insulinoma surgery in MEN1 patients is effective and safe and needs further validation.

Keywords

MEN1 - exendin - GLP1 - surgical outcomes - insulinoma - endogenous hyperinsulinemic hypoglycemia

Supplementary Material



Publication History

Received: 24 April 2025

Accepted after revision: 23 May 2025

Accepted Manuscript online:
23 May 2025

Article published online:
23 June 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Hofland J, Refardt JC, Feelders RA. et al. Approach to the patient: insulinoma. J Clin Endocrinol Metab 2024; 109: 1109-1118
    Search in Google Scholar
  • 2 Shah R, Garg R, Majmundar M. et al. Exendin-4-based imaging in insulinoma localization: systematic review and meta-analysis. Clin Endocrinol (Oxf) 2021; 95: 354-364
    Search in Google Scholar
  • 3 Guettier J-M, Kam A, Chang R. et al. Localization of insulinomas to regions of the pancreas by intraarterial calcium stimulation: the NIH experience. J Clin Endocrinol Metab 2009; 94: 1074-1080
    Search in Google Scholar
  • 4 van Beek DJ, Nell S, Verkooijen HM. et al. Surgery for multiple endocrine neoplasia type 1-related insulinoma: long-term outcomes in a large international cohort. Br J Surg 2020; 107: 1489-1499
    Search in Google Scholar
  • 5 Triponez F, Sadowski SM, Pattou F. et al. Long-term follow-up of MEN1 patients who do not have initial surgery for small≤2 cm nonfunctioning pancreatic neuroendocrine tumors, an AFCE and GTE study: Association Francophone de Chirurgie Endocrinienne & Groupe d’Etude des Tumeurs Endocrines. Ann Surg 2018; 268: 158-16
    Search in Google Scholar
  • 6 Chatzipanagiotou O, Schizas D, Vailas M. et al. All you need to know about gastrinoma today | gastrinoma and Zollinger-Ellison syndrome: a thorough update. J Neuroendocrinol 2023; 35: e13267
    Search in Google Scholar
  • 7 Thakker RV, Newey PJ, Walls GV. et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 2012; 97: 2990-3011
    Search in Google Scholar
  • 8 Christ E, Wild D, Ederer S. et al. Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study. Lancet Diabetes Endocrinol 2013; 1: 115-122
    Search in Google Scholar
  • 9 Luo Y, Pan Q, Yao S. et al. Glucagon-like peptide-1 receptor PET/CT with 68Ga-NOTA-exendin-4 for detecting localized insulinoma: a prospective cohort study. J Nucl Med 2016; 57: 715-720
    Search in Google Scholar
  • 10 Antwi K, Nicolas G, Fani M. et al. 68Ga-Exendin-4 PET/CT detects insulinomas in patients with endogenous hyperinsulinemic hypoglycemia in MEN-1. J Clin Endocrinol Metab 2019; 104: 5843-5852
    Search in Google Scholar
  • 11 Sakurai A, Yamazaki M, Suzuki S. et al. Clinical features of insulinoma in patients with multiple endocrine neoplasia type 1: analysis of the database of the MEN consortium of Japan. Endocr J 2012; 59: 859-866
    Search in Google Scholar
  • 12 Vezzosi D, Cardot-Bauters C, Bouscaren N. et al. Long-term results of the surgical management of insulinoma patients with MEN1: a Groupe d’étude des Tumeurs Endocrines (GTE) retrospective study. Eur J Endocrinol 2015; 172: 309-319
    Search in Google Scholar
  • 13 Zhao Y, Yu J, Liu Y. et al. Analysis of 55 patients with multiple endocrine neoplasia type 1-associated insulinoma from a single center in China. Orphanet J Rare Dis 2022; 17: 219
    Search in Google Scholar
  • 14 Vesterinen T, Peltola E, Leijon H. et al. Immunohistochemical glucagon-like peptide-1 receptor expression in human insulinomas. Int J Mol Sci 2023; 24: 15164
    Search in Google Scholar
  • 15 Erichsen TD, Detlefsen S, Andersen KØ. et al. Occult insulinoma, glucagonoma and pancreatic endocrine pseudotumour in a patient with multiple endocrine neoplasia type 1. Pancreatology 2020; 20: 293-296
    Search in Google Scholar
  • 16 Liang M, Jiang J, Dai H. et al. Robotic enucleation for pediatric insulinoma with MEN1 syndrome: a case report and literature review. BMC Surg 2018; 18: 44
    Search in Google Scholar
  • 17 Sowa-Staszczak A, Pach D, Mikołajczak R. et al. Glucagon-like peptide-1 receptor imaging with [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 for the detection of insulinoma. Eur J Nucl Med Mol Imaging 2013; 40: 524-531
    Search in Google Scholar
  • 18 Xu J, Xu X, Zhang M. et al. Heterogeneity of multiple pancreatic neuroendocrine tumors identified by 68Ga-DOTANOC and 68Ga-exendin-4 PET/CT in a patient with endogenous hyperinsulinemic hypoglycemia and multiple endocrine neoplasia 1. Neuroendocrinology 2024; 114: 866-871
    Search in Google Scholar
  • 19 Kent LA, Gill GV, Williams G. Mortality and outcome of patients with brittle diabetes and recurrent ketoacidosis. Lancet 1994; 344: 778-781
    Search in Google Scholar
  • 20 Roy A, Sahoo J, Kamalanathan S. et al. Islet cell dysfunction in patients with chronic pancreatitis. World J Diabetes 2020; 11: 280-292
    Search in Google Scholar
  • 21 Ichida H, Imamura H, Takahashi A. et al. Evaluation of pancreatic morphometric parameters, exocrine function, and nutritional status and their causal relationships in long-term survivors following pancreatectomy. Surgery 2024; 176: 1189-1197
    Search in Google Scholar
  • 22 Sada A, Habermann EB, Szabo Yamashita T. et al. Comparison between sporadic and multiple endocrine neoplasia type 1-associated insulinoma. J Am Coll Surg 2022; 235: 756-763
    Search in Google Scholar