Case Presentation

The patient (ML) was followed at the Mayo Clinic in Rochester, Minnesota, from 2009 to 2012, at The University of Texas MD Anderson Cancer Center from 2013 to 2016, and at Intermountain Healthcare of Utah from 2017 onward.

ML is a 41 year old male who, in August 2009 at the age of 30 years, presented to his internist with abdominal pain and hypercalcemia of 10.8 mg/dL (normal range, 8.9-10.1 mg/dL). He had facial angiofibromas and lipomas. Laboratory testing revealed an inappropriately normal intact parathyroid hormone (iPTH) level of 44 pg/mL (normal range, 15-65 pg/mL), a normal 25-hydroxy vitamin D3 level of 33 ng/mL (normal range, 25-80 ng/mL), and high-normal 24-hour urinary calcium of level 237 mg (normal range, 25-300 mg), which was concerning for primary hyperparathyroidism (PHPT). He reported a family history of nephrolithiasis, constipation, and metastatic thymic neuroendocrine tumor (NET) in his father and pituitary macroadenoma in his paternal uncle. He underwent germline genetic testing that found a heterozygous, pathogenic variant in the MEN1 gene, confirming a diagnosis of MEN1.

In addition to PHPT, his fasting laboratory tests showed an elevated pancreatic polypeptide (PP) level of 1600 pg/mL (normal, ≤ 249 pg/mL) with normal gastrin, insulin, C-peptide, chromogranin A (CgA), prolactin, and insulin-like growth factor 1 (IGF-1) levels. Endoscopic ultrasound (EUS) in October 2009 identified 1.0 cm and 1.2 cm solid lesions in the head and tail of the pancreas, respectively, and multiple 2 mm to 3 mm hyperechoic lesions. Fine-needle aspiration (FNA) of the head of pancreas lesion was consistent with a well differentiated grade 1 (Ki-67 2%) pancreatic NET (pNET).

In 2011, dual energy x-ray absorptiometry (DXA) demonstrated decreased bone mineral density for age at the lumbar spine (T-score, −2.9; Z-score, −2.7) and otherwise normal BMD. He underwent a subtotal parathyroidectomy and bilateral cervical thymectomy in November 2011. Subsequent serum calcium and iPTH levels have remained within normal limits.

The patient's initial chest computed tomography (CT) in 2009 and subsequent images were without evidence of a thoracic NET. Pituitary magnetic resonance imaging (MRI) in 2009 was normal, but repeat MRI in 2012 identified a possible 2.3 mm pituitary microadenoma (Fig. 1) that has remained stable. Pituitary hormone levels have always been normal.

The multifocal pNETs were followed with alternating EUS and abdominal MRI. By 2016, the pancreatic head NET had grown in size to 1.9 cm and, by July 2017, the same lesion had grown further to 3.0 cm (Fig. 2). He underwent a pylorus-preserving pancreaticoduodenectomy in August 2017. Pathology documented a 2.1 cm well differentiated grade 2 (Ki-67 4.7%) NET and innumerable microadenomas (pT2N0M0). His postoperative course was complicated by delayed gastric emptying. He is followed by yearly abdominal MRI, which shows stable lesions in the pancreatic remnant.

The patient has 2 healthy children, both of whom underwent predictive genetic testing. His daughter was negative for the familial MEN1 variant, whereas predictive testing in his son at age 2 years was positive. His son undergoes annual clinical and laboratory assessment and is without MEN1 manifestations.

中文翻译：

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这不是一个谜，它在历史上：1 型多发性内分泌瘤的多学科管理

案例展示

患者 (ML) 于 2009 年至 2012 年在明尼苏达州罗切斯特的梅奥诊所、​​2013 年至 2016 年在德克萨斯大学 MD 安德森癌症中心以及从 2017 年起在犹他州 Intermountain Healthcare 接受了随访。

ML 是一名 41 岁的男性，他于 2009 年 8 月在 30 岁时因腹痛和高钙血症 10.8 mg/dL（正常范围，8.9-10.1 mg/dL）就诊于他的内科医生。他患有面部血管纤维瘤和脂肪瘤。实验室检测显示不适当的正常完整甲状旁腺激素 (iPTH) 水平为 44 pg/mL（正常范围，15-65 pg/mL），正常的 25-羟基维生素 D3 水平为 33 ng/mL（正常范围，25-80 ng/mL)，以及 24 小时尿钙的正常高值水平 237 毫克（正常范围，25-300 毫克），这与原发性甲状旁腺功能亢进 (PHPT) 相关。他报告了他父亲的肾结石、便秘和转移性胸腺神经内分泌肿瘤 (NET) 和他的叔叔的垂体大腺瘤家族史。他接受了种系基因检测，发现了一个杂合的致病性变异。MEN1基因，确认 MEN1 的诊断。

除了 PHPT，他的空腹实验室检查显示胰多肽 (PP) 水平升高 1600 pg/mL（正常，≤ 249 pg/mL），胃泌素、胰岛素、C 肽、嗜铬粒蛋白 A (CgA)、催乳素、和胰岛素样生长因子 1 (IGF-1) 水平。2009 年 10 月的超声内镜 (EUS) 分别在胰腺头部和尾部发现了 1.0 cm 和 1.2 cm 的实性病变，以及多个 2 mm 至 3 mm 的高回声病变。胰头病变的细针穿刺 (FNA) 与分化良好的 1 级 (Ki-67 2%) 胰腺 NET (pNET) 一致。

2011 年，双能 X 射线吸收测定法 (DXA) 显示腰椎随年龄增长的骨矿物质密度降低（T 分数，-2.9；Z 分数，-2.7），其他方面 BMD 正常。他于 2011 年 11 月接受了次全甲状旁腺切除术和双侧宫颈胸腺切除术。随后的血清钙和 iPTH 水平保持在正常范围内。

患者 2009 年的初始胸部计算机断层扫描 (CT) 和随后的图像均没有胸椎 NET 的证据。2009 年的垂体磁共振成像 (MRI) 是正常的，但 2012 年的重复 MRI 发现了一个可能的 2.3 mm 垂体微腺瘤（图 1），但一直保持稳定。垂体激素水平一直正常。

多焦点 pNET 之后进行了交替的 EUS 和腹部 MRI。到 2016 年，胰头 NET 的大小已增长到 1.9 厘米，到 2017 年 7 月，相同的病变进一步增长到 3.0 厘米（图 2）。他于 2017 年 8 月接受了保留幽门的胰十二指肠切除术。 病理学记录了 2.1 cm 分化良好的 2 级 (Ki-67 4.7%) NET 和无数微腺瘤 (pT2N0M0)。他的术后病程因胃排空延迟而变得复杂。随后每年进行一次腹部 MRI，显示胰腺残余物的稳定病变。

该患者有 2 个健康的孩子，他们都接受了预测性基因检测。他的女儿对家族性MEN1变异呈阴性，而他儿子 2 岁时的预测测试呈阳性。他的儿子每年接受一次临床和实验室评估，并且没有 MEN1 表现。