Abstract
Insulinoma is a rare cause of non-ketotic hypoglycemia, both in adults and in children. Pediatric patients account for approximately 5% of all cases, mostly due to isolated benign lesions, but insulinoma may also be part of a multiple endocrine neoplasia type 1 (MEN1) syndrome. We report the case of a patient with multiple hospitalizations related to hypoglycemia and neuroglycopenia symptoms. Multiple studies demonstrated the presence of an insulinoma. Subsequently, an unreported likely pathogenic variant in the MEN1 gene was identified, suggesting that the clinical presentation of this patient should be part of the spectrum of MEN1 syndrome. The primary significance of this report is to underscore that insulinoma may present as the initial manifestation of MEN1 syndrome, reported to account for around 10% of pediatric insulinomas which are associated with MEN1 syndrome. Furthermore, we describe a previously unreported, likely pathogenic variant in the MEN1 gene. This report highlights the importance of the convergence of clinical, biochemical and molecular investigations in establishing a precise diagnosis, prognosis, and appropriate follow-up for pediatric patients with insulinoma.
Keywords: Hypoglycemia, insulinoma, pediatrics, MEN1 syndrome
Read the full text
4 sections · 2 figures · PDF
Create your free account to read the full text.
- Full text with figures and tables
- PDF and supplementary files
- Access on every Galenos journal
One Galenos account works on every Galenos journal site.
References
Gruppuso PA, Schwartz R. Hypoglycemia in children. Pediatr Rev. 1989;11:117-124.
Gϋemes M, Rahman SA, Kapoor RR, Flanagan S, Houghton JAL, Misra S, Oliver N, Dattani MT, Shah P. Hyperinsulinemic hypoglycemia in children and adolescents: recent advances in understanding of pathophysiology and management. Rev Endocr Metab Disord. 2020;21:577-597.
Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussain K, Levitsky LL, Murad MH, Rozance PJ, Simmons RA, Sperling MA, Weinstein DA, White NH, Wolfsdorf JI; Pediatric Endocrine Society. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of persistent hypoglycemia in neonates, infants, and children. J Pediatr. 2015;167:238-245. Epub 2015 May 6.
Thompson-Branch A, Havranek T. Neonatal hypoglycemia. Pediatr Rev. 2017;38:147-157.
Shah P, Rahman SA, Demirbilek H, Güemes M, Hussain K. Hyperinsulinaemic hypoglycaemia in children and adults. Lancet Diabetes Endocrinol. 2017;5:729-742. Epub 2016 Dec 1.
Stawarski A, Maleika P. Neuroendocrine tumors of the gastrointestinal tract and pancreas: is it also a challenge for pediatricians? Adv Clin Exp Med. 2020;29:265-270.
Yamada Y, Kitayama K, Oyachi M, Higuchi S, Kawakita R, Kanamori Y, Yorifuji T. Nationwide survey of endogenous hyperinsulinemic hypoglycemia in Japan (2017-2018): congenital hyperinsulinism, insulinoma, non-insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata’s disease). J Diabetes Investig. 2020;11:554-563. Epub 2019 Dec 24.
Gaiani F, De’Angelis N, Kayali S, Manfredi M, Di Mario F, Leandro G, Ghiselli A, Fornaroli F, De’Angelis GL. Clinical approach to the patient with acute gastrointestinal bleeding. Acta Biomed. 2018;89:12-19.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-424. Epub 2015 Mar 5.
Service FJ, McMahon MM, O’Brien PC, Ballard DJ. Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin Proc. 1991;66:711-719.
Saneifard H, Khaleghnejad Tabari A, Kazemi Aghdam M, Musavi Khorshidi M, Sheikhy A. Sporadic insulinoma as a rare cause of recurrent hypoglycemia in children. Case Rep Pediatr. 2017;2017:4756793. Epub 2017 Apr 20.
Liang M, Jiang J, Dai H, Hong X, Han X, Cong L, Tong A, Li F, Luo Y, Liu W, Zhou L, Di W, Wu W, Zhao Y. Robotic enucleation for pediatric insulinoma with MEN1 syndrome: a case report and literature review. BMC Surg. 2018;18:44.
Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML; Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97:2990-3011. Epub 2012 Jun 20.
Chavoshi V, Tamehri Zadeh SS, Khalili S, Rabbani A, Matini SAH, Mohsenifar Z, Hadaegh F. Long delay in diagnosis of a case with MEN1 due to concomitant presence of AIMAH with insulinoma: a case report and literature review. BMC Endocr Disord. 2022;22:108.
Thakker RV. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol Cell Endocrinol. 2014;386:2-15. Epub 2013 Aug 8.
Carroll RW. Multiple endocrine neoplasia type 1 (MEN1). Asia Pac J Clin Oncol. 2013;9:297-309. Epub 2012 Dec 26.
Brandi ML, Agarwal SK, Perrier ND, Lines KE, Valk GD, Thakker RV. Multiple endocrine neoplasia type 1: latest insights. Endocr Rev. 2021;42:133-170.
Thevenon J, Bourredjem A, Faivre L, Cardot-Bauters C, Calender A, Le Bras M, Giraud S, Niccoli P, Odou MF, Borson-Chazot F, Barlier A, Lombard-Bohas C, Clauser E, Tabarin A, Pasmant E, Chabre O, Castermans E, Ruszniewski P, Bertherat J, Delemer B, Christin-Maitre S, Beckers A, Guilhem I, Rohmer V, Goichot B, Caron P, Baudin E, Chanson P, Groussin L, Du Boullay H, Weryha G, Lecomte P, Schillo F, Bihan H, Archambeaud F, Kerlan V, Bourcigaux N, Kuhn JM, Vergès B, Rodier M, Renard M, Sadoul JL, Binquet C, Goudet P. Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d’étude des Tumeurs Endocrines study. Eur J Endocrinol. 2015;173:819-826. Epub 2015 Sep 21.
Niederle B, Selberherr A, Bartsch DK, Brandi ML, Doherty GM, Falconi M, Goudet P, Halfdanarson TR, Ito T, Jensen RT, Larghi A, Lee L, Öberg K, Pavel M, Perren A, Sadowski SM, Tonelli F, Triponez F, Valk GD, O’Toole D, Scott-Coombes D, Thakker RV, Thompson GB, Treglia G, Wiedenmann B. Multiple endocrine neoplasia type 1 and the pancreas: diagnosis and treatment of functioning and non-functioning pancreatic and duodenal neuroendocrine neoplasia within the MEN1 syndrome - An International Consensus Statement. Neuroendocrinology. 2021;111:609-630. Epub 2020 Sep 24.
Padidela R, Fiest M, Arya V, Smith VV, Ashworth M, Rampling D, Newbould M, Batra G, James J, Wright NB, Dunne MJ, Clayton PE, Banerjee I, Hussain K. Insulinoma in childhood: clinical, radiological, molecular and histological aspects of nine patients. Eur J Endocrinol. 2014;170:741-747.
Bhatti TR, Ganapathy K, Huppmann AR, Conlin L, Boodhansingh KE, MacMullen C, Becker S, Ernst LM, Adzick NS, Ruchelli ED, Ganguly A, Stanley CA. Histologic and molecular profile of pediatric insulinomas: evidence of a paternal parent-of-origin effect. J Clin Endocrinol Metab. 2016;101:914-922. Epub 2016 Jan 12.
