Severe hypoglycemia in a course of inoperable insulinoma may be life-threating and often it is not well controlled, even by high doses of diazoxide requiring second line treatment. Among available methods PRRT is characterized by relatively low toxicity and is connected with favorable antitumor effect. The aim of the study was an evaluation of the PRRT effectiveness in control of hypoglycemia in patients with primary inoperable insulinoma.
Three patients (female with metastatic insulinoma, male with primary inoperable pancreatic tumor, female with MEN1 syndrome and hepatic metastases) were treated with PRRT due to severe hypoglycemia poorly controlled by diazoxide in course of primary inoperable insulinoma.
Patient 1 baseline fasting glucose concentration increased from 2.4 mmol/L [3.30–5.60] to 5.9 mmol/L after PRRT. In patient 2 fasting glucose level 2.30 mmol/L increased after PRRT to 7.0 mmol/L, while baseline insulin level initially 31.15 uU/mL [2.6–24.9] decreased to 15.4 uU/mL. In patients 3, baseline fasting glucose level 2.5 mmol/L increased after PRRT to 7.9 mmol/L, and insulin decreased from 57.9 uU/mL to 6.3 uU/mL. In imaging there was partial response (PR) in patient 1 and 2 and stabilization of the tumor size in patient 3. In patient 2 reduction of tumor infiltration let for curative surgery performed 4 months after PPRT.
PRRT may be effective as a first or second line treatment in management of hypoglycemia for patients with hormonally active inoperable insulinoma.
Research funding: None declared.
Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Not applicable.
Ethical approval: Research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki.
1. Falconi, M, Eriksson, B, Kaltsas, G, Bartsch, DK, Capdevila, J, Caplin, M, et al.. ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology 2016;103:153–71. https://doi.org/10.1159/000443171.Search in Google Scholar
2. Hofland, J, Feelders, RA, Brabander, T, Franssen, GJH, de Herder, WW. Recent developments in the diagnosis and therapy of well-differentiated neuroendocrine tumours. Neth J Med 2018;76:100–8.Search in Google Scholar
3. de Herder, WW, Zandee, WT, Hofland, J. Insulinoma. In: Feingold, KR, Anawalt, B, Boyce, A, Chrousos, G, de Herder, WW, Dhatariya, K, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000, PMID:25905215 p.10.1159/000080735Search in Google Scholar PubMed
4. Kunikowska, J, Słodkowski, M, Koperski, Ł, Kolasa, A, Maryański, J, Pawliszak, P, et al.. Radioguided surgery in patient with pancreatic neuroendocrine tumour followed by PET/CT scan as a new approach of complete resection evaluation-case report. Nucl Med Rev Cent East Eur 2014;17:110–4. https://doi.org/10.5603/NMR.2014.0028.Search in Google Scholar
5. Brand, C, Abdel-Atti, D, Zhang, Y, Carlin, S, Clardy, SM, Keliher, EJ, et al.. In vivo imaging of GLP-1R with a targeted bimodal PET/fluorescence imaging agent. Bioconjug Chem 2014;25:1323–30. https://doi.org/10.1021/bc500178d.Search in Google Scholar
6. Mehrabi, A, Fischer, L, Hafezi, M, Dirlewanger, A, Grenacher, L, Diener, MK, et al.. A systematic review of localization, surgical treatment options, and outcome of insulinoma. Pancreas 2014;43:675–86. https://doi.org/10.1097/mpa.0000000000000110.Search in Google Scholar
7. Guo, Q, Wu, Y. Surgical treatment of pancreatic islet cell tumor: report of 44 cases. Hepato-Gastroenterology 2013;60:2099–102.Search in Google Scholar
8. Niitsu, Y, Minami, I, Izumiyama, H, Hashimoto, K, Yoshimoto, T, Satou, F, et al.. Clinical outcomes of 20 Japanese patients with insulinoma treated with diazoxide. Endocr J 2019;66:149–55. https://doi.org/10.1507/endocrj.ej18-0353.Search in Google Scholar
9. Hofland, J, Kaltsas, G, de Herder, WW. Advances in the diagnosis and management of well-differentiated neuroendocrine neoplasms. Endocr Rev 2020;41:371–403. https://doi.org/10.1210/endrev/bnz004.Search in Google Scholar
10. Pavel, M, Öberg, K, Falconi, M, Krenning, EP, Sundin, A, Perren, A, et al.. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. ESMO Guidelines Committee. Electronic address: email@example.com. Ann Oncol 2020;31:844–60. https://doi.org/10.1016/j.annonc.2020.03.304.Search in Google Scholar
11. Bodei, L, Mueller-Brand, J, Baum, RP, Pavel, ME, Horsch, D, O’Dorisio, MS, et al.. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imag 2013;40:800–16. https://doi.org/10.1007/s00259-012-2330-6.Search in Google Scholar
12. Gomes-Porras, M, Cárdenas-Salas, J, Álvarez-Escolá, C. Somatostatin analogs in clinical practice: a review. Int J Mol Sci 2020;21:1682. https://doi.org/10.3390/ijms21051682.Search in Google Scholar
13. Veltroni, A, Cosaro, E, Spada, F, Fazio, N, Faggiano, A, Colao, A, et al.. Clinico-pathological features, treatments and survival of malignant insulinomas: a multicenter study. Eur J Endocrinol 2020;182:439–46. https://doi.org/10.1530/eje-19-0989.Search in Google Scholar
14. Spada, F, Rossi, RE, Kara, E, Laffi, A, Massironi, S, Rubino, M, et al.. Carcinoid syndrome and hyperinsulinemic hypoglycemia associated with neuroendocrine neoplasms: a critical review on clinical and pharmacological management. Pharmaceuticals 2021;14:539. https://doi.org/10.3390/ph14060539.Search in Google Scholar
15. Gilis-Januszewska, A, Bogusławska, A, Hasse-Lazar, K, Jurecka-Lubieniecka, B, Jarząb, B, Sowa-Staszczak, A, et al.. Heterogeneity of the clinical presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) variant within a three-generation family. Genes 2021;12:512. https://doi.org/10.3390/genes12040512.Search in Google Scholar
17. Mapelli, P, Partelli, S, Salgarello, M, Doraku, J, Muffatti, F, Schiavo Lena, M, et al.. Dual tracer 68Ga-DOTATOC and 18F-FDG PET improve preoperative evaluation of aggressiveness in resectable pancreatic neuroendocrine neoplasms. Diagnostics 2021;11:192. https://doi.org/10.3390/diagnostics11020192.Search in Google Scholar
18. Calabrò, D, Argalia, G, Ambrosini, V. Role of PET/CT and therapy management of pancreatic neuroendocrine tumors. Diagnostics 2020;10:1059.10.3390/diagnostics10121059Search in Google Scholar PubMed PubMed Central
19. Reubi, JC, Schär, JC, Waser, B, Wenger, S, Heppeler, A, Schmitt, JS, et al.. Affinity profiles for human somatostatin re-ceptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and ra-diotherapeutic use. Eur J Nucl Med 2000;27:273–82. https://doi.org/10.1007/s002590050034.Search in Google Scholar
20. Krenning, EP, Kwekkeboom, DJ, Bakker, WH, Breeman, WA, Kooij, PP, Oei, HY, et al.. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993;20:716–31. https://doi.org/10.1007/bf00181765.Search in Google Scholar
21. Antwi, K, Fani, M, Heye, T, Nicolas, G, Rottenburger, C, Kaul, F, et al.. Comparison of glucagon-like peptide-1 receptor (GLP-1R) PET/CT, SPECT/CT and 3T MRI for the localisation of occult insulinomas: evaluation of diagnostic accuracy in a prospective crossover imaging study. Eur J Nucl Med Mol Imag 2018;45:2318–27. https://doi.org/10.1007/s00259-018-4101-5.Search in Google Scholar
22. Sowa-Staszczak, A, Trofimiuk-Müldner, M, Stefańska, A, Tomaszuk, M, Buziak-Bereza, M, Gilis-Januszewska, A, et al.. 99mTc labeled glucagon-like peptide-1-analogue (99mTc-GLP1) scintigraphy in the management of patients with occult insulinoma. PLoS One 2016;11:e0160714. https://doi.org/10.1371/journal.pone.0160714.Search in Google Scholar
23. Christ, E, Antwi, K, Fani, M, Wild, D. Innovative imaging of insulinoma: the end of sampling? A review. Endocr Relat Cancer. 2020;27:R79–92. https://doi.org/10.1530/erc-19-0476.Search in Google Scholar
24. Magalhães, D, Sampaio, IL, Ferreira, G, Bogalho, P, Martins-Branco, D, Santos, R, et al.. Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE as a promising treatment of malignant insulinoma: a series of case reports and literature review. J Endocrinol Invest 2019;42:249–60. https://doi.org/10.1007/s40618-018-0911-3.Search in Google Scholar
25. Zandee, WT, Brabander, T, Blažević, A, Kam, BLR, Teunissen, JJM, Feelders, RA, et al.. Symptomatic and radiological response to 177Lu-DOTATATE for the treatment of functioning pancreatic neuroendocrine tumors. J Clin Endocrinol Metab 2019;104:1336–44. https://doi.org/10.1210/jc.2018-01991.Search in Google Scholar
26. Yao, JC, Fazio, N, Singh, S, Buzzoni, R, Carnaghi, C, Wolin, E, et al.. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. RAD001 in Advanced Neuroendocrine Tumours, Fourth Trial (RADIANT-4) Study Group. Lancet 2016;387:968–77. https://doi.org/10.1016/s0140-6736(15)00817-x.Search in Google Scholar
27. Strosberg, JR, Caplin, ME, Knuz, PL, Ruszniewski, P, Bodei, L, Hendifar, AE, et al.. Final overall survival in the phase 3 NETTER-1 study of lutetium-177-DOTATATE in patients with midgut neuroendocrine tumors. J Clin Oncol 2021;39(15 Suppl): 4112. https://doi.org/10.1200/jco.2021.39.15_suppl.4112.Search in Google Scholar
28. Starr, JS, Sonbol, MB, Hobday, TJ, Sharma, A, Kendi, AT, Halfdanarson, TR. Peptide receptor radionuclide therapy for the treatment of pancreatic neuroendocrine tumors: recent insights. OncoTargets Ther 2020;13:3545–55. https://doi.org/10.2147/ott.s202867.Search in Google Scholar
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