PMID- 37152923 OWN - NLM STAT- MEDLINE DCOM- 20230509 LR - 20230511 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - Insulinoma in childhood: a retrospective review of 22 patients from one referral centre. PG - 1127173 LID - 10.3389/fendo.2023.1127173 [doi] LID - 1127173 AB - BACKGROUND: Insulinomas are very rare in childhood with sparse knowledge on the clinical aspects and the presence of Multiple Endocrine Neoplasia type 1 (MEN1). METHODS: We conducted a retrospective review of patients diagnosed with insulinoma between 1995 and 2021, presenting to one referral centre in Russia. Clinical, biochemical, genetic, imaging and histological data were collected. In addition, follow-up and family data were obtained. RESULTS: A total of twenty-two children aged 5 to 16 years were identified. The median (range) gap between the first hypoglycaemia symptoms and diagnosis was 10 (1-46) months. Twelve children (55%) were misdiagnosed to have epilepsy and were treated with anticonvulsants before hypoglycemia was revealed. Contrast enhanced MRI and/or CT were accurate to localize the lesion in 82% (n=18). Five patients (23%) had multiple pancreatic lesions. All children underwent surgical treatment. The median (range) diameter of removed tumors was 1.5 (0.3-6) cm. Histopathological studies confirmed the presence of insulinoma in all cases. Immunohistochemical studies revealed G2 differentiation grade in 10 out of 17 cases. Two patients were diagnosed with metastatic insulinoma. One of them had metastases at the time of insulinoma diagnosis, while the other was diagnosed with liver metastases eight years after the surgery. Eight children (36%) were found to carry MEN1 mutations, inherited n=5, de novo n=1, no data, n=2. Children with MEN1 had significantly higher number of pancreatic tumors compared to sporadic cases. All of them developed additional MEN1 symptoms during the following 2-13 years. In the five patients with inherited MEN1, seven family members had hitherto undiscovered MEN1 manifestations. CONCLUSIONS: In this large cohort of children with rare pediatric insulinomas, MEN1 syndrome and G2 tumors were frequent, as well as hitherto undiscovered MEN1 manifestations in family members. Our data emphasize the need of genetic testing in all children with insulinoma and their relatives, even in the absence of any other features, as well as the importance of a prolonged follow-up observation. CI - Copyright (c) 2023 Melikyan, Gubaeva, Shadrina, Bolmasova, Kareva, Tiulpakov, Efremenkov, Sokolov, Brusgaard, Christesen, Andersen, Stepanov, Averyanova, Makarov and Gurevich. FAU - Melikyan, Maria AU - Melikyan M AD - Department of Pediatric Endocrinology, Endocrinology Research Center, Moscow, Russia. AD - Department of Endocrinology, Yerevan State Medical University, Yerevan, Armenia. AD - Department of pediatrics, Center of Medical Genetics and Primary Health Care, Yerevan, Armenia. FAU - Gubaeva, Diliara AU - Gubaeva D AD - Department of Pediatric Endocrinology, Endocrinology Research Center, Moscow, Russia. AD - Department of Pediatric Endocrinology, Alder Hey Children's Hospital, Liverpool, United Kingdom. FAU - Shadrina, Anna AU - Shadrina A AD - Department of Pediatric Endocrinology, Endocrinology Research Center, Moscow, Russia. FAU - Bolmasova, Anna AU - Bolmasova A AD - Department of Pediatric Endocrinology, Endocrinology Research Center, Moscow, Russia. FAU - Kareva, Maria AU - Kareva M AD - Department of Pediatric Endocrinology, Endocrinology Research Center, Moscow, Russia. FAU - Tiulpakov, Anatoly AU - Tiulpakov A AD - Department of Pediatric Endocrinology, Endocrinology Research Center, Moscow, Russia. AD - Department of Endocrinology, Federal State Budgetary Scientific Institution Research Centre for Medical Genetics (RCMG), Moscow, Russia. FAU - Efremenkov, Artem AU - Efremenkov A AD - Department of Pediatric Surgery, Central Clinical Hospital, Moscow, Russia. FAU - Sokolov, Yuri AU - Sokolov Y AD - Department of Pediatric Surgery, Endocrinology Research Center, Moscow, Russia. FAU - Brusgaard, Klaus AU - Brusgaard K AD - Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. AD - Odense Pancreas Center OPAC and Steno Diabetes Center Odense, Odense, Denmark. AD - Department of Endocrinology, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark. FAU - Christesen, Henrik T AU - Christesen HT AD - Odense Pancreas Center OPAC and Steno Diabetes Center Odense, Odense, Denmark. AD - Department of Endocrinology, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark. AD - Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Andersen, Kirstine AU - Andersen K AD - Odense Pancreas Center OPAC and Steno Diabetes Center Odense, Odense, Denmark. AD - Department of Endocrinology, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark. AD - Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Stepanov, Alexey AU - Stepanov A AD - Department of Abdominal Surgery, Russian Children's Clinical Hospital, Moscow, Russia. FAU - Averyanova, Julia AU - Averyanova J AD - Department of Abdominal Surgery, Russian Children's Clinical Hospital, Moscow, Russia. FAU - Makarov, Sergey AU - Makarov S AD - Department of Abdominal Surgery, Russian Children's Clinical Hospital, Moscow, Russia. FAU - Gurevich, Larisa AU - Gurevich L AD - Morphological Department of Oncology, State Budget Health Agency Moscow Region Moscow Regional Research Clinical Institute, Moscow, Russia. LA - eng PT - Journal Article DEP - 20230419 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 SB - IM MH - Humans MH - Child MH - *Insulinoma/diagnosis/genetics/pathology MH - Retrospective Studies MH - *Multiple Endocrine Neoplasia Type 1/genetics MH - *Pancreatic Neoplasms/diagnosis/genetics/pathology MH - *Hypoglycemia MH - Referral and Consultation PMC - PMC10155867 OTO - NOTNLM OT - Multiple Endocrine Neoplasia type 1 (MEN1) OT - hyperinsulinemic hypoglycemia OT - insulinoma OT - malignant insulinoma OT - pancreatic NETs COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/05/08 06:41 MHDA- 2023/05/09 10:16 PMCR- 2023/01/01 CRDT- 2023/05/08 04:10 PHST- 2022/12/19 00:00 [received] PHST- 2023/03/27 00:00 [accepted] PHST- 2023/05/09 10:16 [medline] PHST- 2023/05/08 06:41 [pubmed] PHST- 2023/05/08 04:10 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1127173 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Apr 19;14:1127173. doi: 10.3389/fendo.2023.1127173. eCollection 2023.