Machens Andreas, Schaaf Ludwig, Karges Wolfram, Frank-Raue Karin, Bartsch Detlef K, Rothmund Matthias, Schneyer Ulrich, Goretzki Peter, Raue Friedhelm, Dralle Henning
Department of General, Visceral and Vascular Surgery, Martin-Luther-University, Halle (Saale), Germany.
Clin Endocrinol (Oxf). 2007 Oct;67(4):613-22. doi: 10.1111/j.1365-2265.2007.02934.x. Epub 2007 Jun 21.
In multiple endocrine neoplasia type 1 (MEN1), age-related tumour penetrance according to the type of MEN1 germline mutation has not been investigated in-depth. This study was conducted to examine whether carriers of out-of-frame/truncating and in-frame MEN1 mutations differ in age-related tumour penetrance.
A multicentre study with biochemical, hormonal and radiological screening for MEN1-associated tumours.
A total of 258 MEN1 carriers from six major German tertiary referral centres averaging 43 years of age at last follow-up.
Main outcome measure was time to first diagnosis of MEN1-associated tumours.
Independent of the year of birth and observation period, time to first tumour diagnosis did not vary much by the type of MEN1 germline mutation or endocrine organ system, and perhaps not even by the type of endocrine tumour when the amount of time was considered by which the diagnosis probably has been advanced through the manifestation of hormonal symptoms. Parathyroid hyperplasia and adenomas developed almost twice as often as enteropancreatic and pituitary tumours (77%vs. 49-32%), and more than five to sevenfold as often as adrenal cortical tumours and carcinoids (77%vs. 15-10%), reaching penetrance rates of up to 90%, 60%, 40%, 26% and 17%, respectively. The heterogeneity of tumour penetrance was marked, ranging from 9 years to 25 years for the earliest, and from 68 years to 77 years for the latest tumour manifestation.
Because of our inability of predicting tumour penetrance and malignant transformation individually, life-long follow-up of MEN1 carriers is warranted to prevent tumour morbidity.
在1型多发性内分泌腺瘤病（MEN1）中，尚未对根据MEN1种系突变类型的年龄相关肿瘤外显率进行深入研究。本研究旨在探讨框外/截短型和框内MEN1突变携带者在年龄相关肿瘤外显率方面是否存在差异。
一项多中心研究，对MEN1相关肿瘤进行生化、激素和放射学筛查。
来自德国六个主要三级转诊中心的258名MEN1携带者，最后一次随访时平均年龄为43岁。
主要结局指标是首次诊断MEN1相关肿瘤的时间。
独立于出生年份和观察期，首次肿瘤诊断的时间在MEN1种系突变类型或内分泌器官系统方面变化不大，当考虑到因激素症状表现而可能提前诊断的时间量时，甚至在内分泌肿瘤类型方面变化也不大。甲状旁腺增生和腺瘤的发生频率几乎是肠胰腺和垂体肿瘤的两倍（77%对49%-32%），是肾上腺皮质肿瘤和类癌的五到七倍多（77%对15%-10%），其外显率分别高达90%、60%、40%、26%和17%。肿瘤外显率的异质性很明显，最早的肿瘤表现为9岁至25岁，最晚的为68岁至77岁。
由于我们无法单独预测肿瘤外显率和恶性转化，因此有必要对MEN1携带者进行终身随访以预防肿瘤发病。
