多灶性胰岛素瘤是一名青少年 MEN1 的独特表现特征。

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Alison Murray, Sonia Priscila Rodas Marquez, Mansa Krishnamurthy, Oscar Lopez-Nunez, Juan P Gurria, Andrew T Trout, Susan Almazan, Krishnamallika Mutyala, Gabriella Grisotti, Amy Shah, Jonathan Howell
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引用次数: 0

摘要

导言:多发性内分泌肿瘤症 1 型(MEN1)是一种常染色体显性遗传疾病,定义为存在以下两种内分泌疾病:原发性甲状旁腺功能亢进症、垂体前叶肿瘤和十二指肠胰腺神经内分泌肿瘤(NET)。NET可分泌包括胰岛素、胃泌素和胰高血糖素等激素,在MEN1患者中很常见,是发病和过早死亡的主要原因。NET在晚期更为常见,儿童病例极少。在此,我们描述了一例独特的青少年病例,该病例以多灶性胰腺 NET 为 MEN1 的单一表现特征。病例介绍 一名 13 岁的健康男性患者出现严重乏力、精神状态改变和晕厥,静脉血糖(BG)为 36 毫克/分升。检查结果显示,当血糖为 39 mg/dL 时,胰岛素水平升高(14 mcIU/mL),对胰高血糖素的反应呈阳性,考虑为胰岛素分泌过多症。患者开始服用地亚索和氯噻嗪,但因呕吐而不能耐受。通过核磁共振成像和68-Ga DOTATATE PET-CT成像,确定了三个疑似NET,其中最大的是胰腺头部一个2.1厘米的肿块。术中超声检查发现了胰腺尾部的第四个肿块。所有病灶均被成功切除,术后第 2 天服用二氮嗪后血糖水平恢复正常。原发病灶通过免疫荧光(IF)检测出胰岛素和体节素染色,这与他的临床表现一致,而其他肿瘤则表达胰高血糖素、体节素、胰多肽和嗜铬粒蛋白 A,但胰岛素检测呈阴性。基因检测证实了 MEN1 基因的致病性杂合突变(c.969C>A,p.Tyr323)。在筛查中,他没有发现其他与 MEN 相关的合并症。讨论/结论 本病例表明,年轻的 MEN1 患者可出现多灶性 NET。尽管临床表现与一种原发性激素一致,但这些NET可能具有多激素表达模式。我们的患者临床症状和实验室评估结果与胰岛素瘤一致,但却发现有四个NET,每个都有不同的IF染色模式。先进的术前和术中成像对于识别和治疗所有存在的NET非常重要。此外,治疗前后的血清激素水平有助于评估 NET 是在向血液中积极分泌激素,还是仅仅在胰腺内表达激素。最后,本病例强调了对所有年轻胰岛素瘤患者进行MEN1基因检测的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multifocal Insulinoma as the Unique Presenting Feature of Multiple Endocrine Neoplasia Type 1 in an Adolescent.

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder defined by the presence of two of the following endocrinopathies: primary hyperparathyroidism, anterior pituitary tumors, and duodenopancreatic neuroendocrine tumors (NETs). NETs, which can secrete hormones including insulin, gastrin, and glucagon, among others, are common in patients with MEN1 and are a major cause of morbidity and premature death. NETs are more common later in life, with very few cases described in children. Here, we describe a unique case of an adolescent with multifocal pancreatic NETs as the single presenting feature of MEN1.

Case presentation: A 13-year-old healthy male presented with severe weakness, altered mental status, and syncope in the setting of a venous blood glucose (BG) of 36 mg/dL. Workup showed an elevated insulin level (14 μIU/mL) when BG was 39 mg/dL with positive response to glucagon, concerning for hyperinsulinism. Diazoxide and chlorothiazide were started but not well tolerated secondary to emesis. Three suspected NETs were identified by magnetic resonance imaging and 68-Ga DOTATATE PET-CT imaging, including the largest, a 2.1 cm mass in the pancreatic head. A fourth mass in the pancreatic tail was identified via intraoperative ultrasound. All lesions were successfully enucleated and excised, and glucose levels normalized off diazoxide by post-op day 2. While the primary lesion stained for insulin and somatostatin by immunofluorescence (IF), consistent with his clinical presentation, the additional tumors expressed glucagon, somatostatin, pancreatic polypeptide, and chromogranin A but were negative for insulin. Genetic testing confirmed a pathogenic heterozygous mutation in MEN1 (c.969C>A, p.Tyr323). He had no other signs of MEN-associated comorbidities on screening.

Discussion/conclusion: This case demonstrates that young patients with MEN1 can present with multifocal NETs. These NETs may have polyhormonal expression patterns despite a clinical presentation consistent with one primary hormone. Our patient had clinical symptoms and laboratory evaluation consistent with an insulinoma but was found to have four NETs, each with different IF staining patterns. Advanced preoperative and intraoperative imaging is important to identify and treat all present NETs. Moreover, serum hormone levels pre- and posttreatment could help evaluate whether NETs are actively secreting hormones into the bloodstream or simply expressing them within the pancreas. Finally, this case highlights the importance of genetic testing for MEN1 in all young patients with insulinomas.

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来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
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