Gibril Fathia, Schumann Michael, Pace Andrea, Jensen Robert T
From Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Medicine (Baltimore). 2004 Jan;83(1):43-83. doi: 10.1097/01.md.0000112297.72510.32.
In patients with multiple endocrine neoplasia type 1 (MEN1), the most common functional pancreatic endocrine tumor (PET) syndrome is Zollinger-Ellison syndrome (ZES). ZES has been well studied in its sporadic form (that is, without MEN1); however, there are limited data on patients with MEN1 and ZES (MEN1/ZES), and the long-term natural history is largely unknown. To address this issue we report the results of a prospective long-term National Institutes of Health (NIH) study of 107 MEN1/ZES patients and compare our results with those of 1009 MEN1/ZES patients in 278 case reports and small series in the literature. Patients were clinically, radiologically, and biochemically evaluated yearly for all MEN1 manifestations (mean follow-up, 10 yr; range, 0.1-31 yr). Compared with patients from the literature, the NIH MEN1/ZES patients more frequently had pituitary (60%) and adrenal (45%) disease and carcinoid tumors (30%), but had equal frequency of hyperparathyroidism (94%), thyroid disease (6%), or lipomas (5%). Twenty-five percent of both the NIH and the literature patients lacked a family history of MEN1; ZES was the initial clinical manifestation of MEN1 in 40%. ZES onset preceded the diagnosis of hyperparathyroidism in 45%. However, ZES was rarely (8%) the only initial manifestation of MEN1 if careful testing was done. ZES occurred before age 40 years in 50%-60% of the current patients, in contrast to older studies. The diagnosis of ZES is delayed 3-5 years from its onset and is delayed as long as in sporadic ZES cases. Pituitary disease and carcinoid tumors (gastric > bronchial, thymic) are more frequent than generally reported, whereas a second functional PET is uncommon. In patients with MEN1/ZES without a family history of MEN1, the MEN1 manifestations are not as severe. This study shows that MEN1/ZES patients differ in many aspects from those commonly reported in older studies involving few MEN1/ZES patients. In this study we have identified a number of important clinical and laboratory features of MEN1/ZES that were not previously appreciated, which should contribute to earlier diagnosis and improve both short- and long-term management.
在1型多发性内分泌腺瘤病（MEN1）患者中，最常见的功能性胰腺内分泌肿瘤（PET）综合征是卓 - 艾综合征（ZES）。ZES的散发性形式（即不伴有MEN1）已得到充分研究；然而，关于MEN1合并ZES（MEN1/ZES）患者的数据有限，其长期自然病史在很大程度上尚不清楚。为解决这一问题，我们报告了美国国立卫生研究院（NIH）一项针对107例MEN1/ZES患者的前瞻性长期研究结果，并将我们的结果与文献中278例病例报告和小样本系列研究中的1009例MEN1/ZES患者的结果进行比较。每年对患者进行临床、影像学和生化评估，以了解所有MEN1表现（平均随访10年；范围0.1 - 31年）。与文献中的患者相比，NIH的MEN1/ZES患者更常出现垂体疾病（60%）、肾上腺疾病（45%）和类癌肿瘤（30%），但甲状旁腺功能亢进（94%）、甲状腺疾病（6%）或脂肪瘤（5%）的发生率相同。NIH患者和文献中的患者均有25%缺乏MEN1家族史；ZES是40%的MEN1患者的初始临床表现。45%的患者中ZES发病先于甲状旁腺功能亢进的诊断。然而，如果进行仔细检查，ZES很少（8%）是MEN1的唯一初始表现。与以往研究相比，当前患者中有50% - 60%在40岁之前发生ZES。ZES从发病到诊断延迟3 - 5年，与散发性ZES病例延迟时间相同。垂体疾病和类癌肿瘤（胃＞支气管、胸腺）比一般报道的更常见，而第二种功能性PET并不常见。在无MEN1家族史的MEN1/ZES患者中，MEN1表现不那么严重。这项研究表明，MEN1/ZES患者在许多方面与以往涉及少数MEN1/ZES患者的研究中所报道的患者不同。在本研究中，我们确定了一些以前未被认识到的MEN1/ZES的重要临床和实验室特征，这将有助于早期诊断并改善短期和长期管理。
