dawnmedDawnMed Journal of Medical ScienceISVolume 2, Issue 2MultidisciplinaryEnglish2026NNY20260531Neurology Look Beyond the Brain: A Case of Insulinomatosis Disguised as Frontal Lobe Epilepsy and Review of the LiteratureEnglishY18SomayaAlbalawi¹EnglishNSuha O.Alzubaidy²EnglishYShatha H. AlKenani²EnglishYBatool S.Bedaiwi³EnglishYRimas A.Alqarni³EnglishYMohammed A.Alhowaish⁴EnglishYIsraa A.Alhawaj⁵EnglishYAbdulbasit M.Bugis⁶EnglishY10.64039/djms.2026.2201Background: Insulinomatosis is a rare and underrecognized cause of endogenous hyperinsulinemic hypoglycemia (EHH) defined by multicentric insulinsecreting pancreatic neuroendocrine tumors (PanNETs) accompanied by diffuse neuroendocrine microadenomatosis. Neuroglycopenic manifestations of hypoglycemia frequently mimic primary neurological and psychiatric disorders, leading to substantial diagnostic delays that adversely affect patient outcomes.Case Presentation: We report a 32-year-old woman who carried a diagnosis of refractory frontal lobe epilepsy for approximately one year before the true etiology was identified. Her recurrent episodes of hypermotor activity, emotional lability, and facial twitching had been attributed to frontal lobe seizures and managed with escalating doses of lamotrigine. The pivotal diagnostic clue emerged when a seizure was documented in association with hypoglycemia (glucose 40–50 mg/dL; 2.2–2.8 mmol/L), prompting continuous glucose monitoring that confirmed recurrent hypoglycemic episodes. A supervised 72-hour fasting test established endogenous hyperinsulinemic hypoglycemia, with inappropriately elevated insulin (66 pmol/L), C-peptide (0.90 nmol/L), and markedly elevated proinsulin (36.01 pmol/L). Contrast-enhanced computed tomography and endoscopic ultrasound identified a dominant lesion in the pancreatic head; however, Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) revealed at least four somatostatin receptor–avid lesions distributed across the head, body, and tail of the pancreas. The patient underwent A Whipple procedure (pancreaticoduodenectomy) with enucleation and resection of additional pancreatic lesions. Final histopathology demonstrated multiple well-differentiated PanNETs of variable sizes with neuroendocrine microadenomatosis throughout the pancreatic parenchyma, consistent with insulinomatosis. Multiple endocrine neoplasia type 1 (MEN1) was excluded on biochemical screening. Postoperatively, hypoglycemia resolved completely and antiseizure medication was discontinued.Conclusion: This case underscores the critical importance of excluding hypoglycemia in patients presenting with atypical or drug-resistant seizures and highlights insulinomatosis as a rare yet clinically significant differential diagnosis. Early recognition of Whipple's triad, coupled with the strategic use of functional imaging such as Ga-68 DOTATATE PET/CT, is essential for guiding timely and definitive surgical management to achieve biochemical cure.EnglishInsulinomatosis; endogenous hyperinsulinemic hypoglycemia; pancreatic neuroendocrine tumor; frontal lobe epilepsy; neuroglycopenia.https://dawnmed.com.sa/abstract?id=13References16191. Mills EA, DeLucia BP, Wayne CD, Jacobs TH, Besner GE. Functional pancreatic neuroendocrine neoplasms. Endocrines. 2025;6(3):38. 2. Hofland J, Refardt JC, Feelders RA, Christ E, de Herder WW. Approach to the patient: insulinoma. J Clin Endocrinol Metab. 2024;109(4):1109and;ndash;1118. 3. Insulinoma. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK54429/. 4. Thakker RV, Newey PJ, Walls GV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990and;ndash;3011.and;nbsp; 5. Anlauf M, Bauersfeld J, Raffel A, et al. Insulinomatosis: a multicentric insulinoma diseaseand;nbsp;that frequently causes early recurrent hyperinsulinemic hypoglycemia. Am J Surg Pathol. 2009;33(3):339and;ndash;346. 6. Anoshkin K, Vasilyev I, Karandasheva K, et al. New regions with molecular alterations in a rare case of insulinomatosis: case report with literature review. Front Endocrinol (Lausanne). 2021; 12:760154. 7. Christ E, Iacovazzo D, Korbonits M, Perren A. Insulinomatosis and;ndash; new aspects. Endocr Relat Cancer. 2023;30(6):e220327. 8. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94(3):709and;ndash;728. 9. Dizon AM, Kowalyk S, Hoogwerf BJ. Neuroglycopenic and other symptoms in patients with insulinomas. Am J Med. 1999;106(3):307and;ndash;310. 10. Ishida H, Lam AK. Pancreatic neuroendocrine neoplasms: updates on genomic changes in inherited tumour syndromes and sporadic tumours based on WHO classification. Crit Rev Oncol Hematol. 2022; 172:103648. 11. Lourenand;ccedil;o DM Jr, Corrand;ecirc;a-Giannella ML, Siqueira SAC, et al. Case report: insulinomatosis: description of four sporadic cases and review of the literature. Front Endocrinol (Lausanne). 2024; 14:1308662. 12. Iacovazzo D, Flanagan SE, Walker E, et al. MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. Proc Natl Acad Sci U S A. 2018;115(5):1027and;ndash;1032. 13. Fottner C, Sollfrank S, Ghiasi M, et al. Second MAFA variant causing a phosphorylation defect in the transactivation domain and familial insulinomatosis. Cancers (Basel). 2022;14(7):1798. 14. Nockel P, Babic B, Millo C, et al. Localization of insulinoma using 68Ga-DOTATATE PET/CT scan. J Clin Endocrinol Metab. 2017;102(1):195and;ndash;199.and;nbsp; 15. Hassan A, Chopra A, Garg R, et al. 68GaDOTATATE PET/CT: how is it reliable in imaging of cases having clinical suspicion of insulinomas? Nucl Med Commun. 2024;45(10):867and;ndash;873. 16. Jaramillo Chacand;oacute;n H, Gonzand;aacute;lez Devia D, Land;oacute;pez Panqueva RP, et al. Insulinomatosis: a very rare cause of pancreatic neuroendocrine tumor. Rev Colomb Endocrinol Diabetes Metab. 2020;7(2):76and;ndash;85. 17. Wang S, Hu HT, Wen SQ, et al. An insulinoma with clinical and electroencephalographic features resembling complex partial seizures. J Zhejiang Univ Sci B. 2008;9(6):496and;ndash;499. 18. Yang L, Xu Q, Li S, et al. Insulinoma presenting as a complex partial seizure: still a possible misleading factor. Front Neurosci. 2019; 13:1388. 19. Bosak M, Sowa-Staszczak A, Słowik A. Insulinoma mimicking psychogenic nonepileptic seizures in a patient with refractory epilepsy. Pol Arch Intern Med. 2019;129(4):290and;ndash;291. 20. Kostolanska N, Klimes P, Kocvarova J, et al. Case report: insulinoma masquerades as epilepsy and;ndash; quantitative EEG analysis. Front Neurol. 2024; 15:1371055. 21. Dixit S, Kumar A, Rai K. Insulinoma presenting as refractory seizure disorder. J Assoc Physicians India. 2013;61(3):206and;ndash;208. 22. Sadowski SM, Millo C, Cottle-Delisle C, et al. Results of 68gallium-DOTATATE PET/CT scanning in patients with multiple endocrine neoplasia type 1. J Am Coll Surg. 2015;221(2):509and;ndash;517. 23. Bettini V, Martini C, Parisi D, et al. Complete remission of recurrent multiple insulin-producing neuroendocrine tumors of the pancreas with somatostatin analogs: a case report and literature review. Discov Oncol. 2022; 13:69.