Steroid profiling as a biomarker tool in the diagnosis and monitoring of adrenal tumours

肾上腺肿瘤很常见，占总人口的1-2%。然而，随着年龄的增长，这些肿瘤变得更加常见，3%的40岁和10%的70岁的人患有肾上腺肿瘤，其中许多人并不知道它。大多数肾上腺肿瘤是偶然发现的，大多是通过CT扫描等成像程序进行的，原因不是可疑的肾上腺疾病。一旦发现，肾上腺结节需要仔细评估，因为它们可能会过度产生激素，对健康产生潜在的有害影响，而且重要的是，它们可能是恶性的，要么源于肾上腺本身，要么代表其他恶性肿瘤的转移。目前，我们在肾上腺肿瘤患者的检查中使用不同的成像程序和血液测试，但这并不总是提供足够的信息，而且通常很难确定肾上腺肿瘤是良性还是恶性。我们已经开发出一种生物标记物工具，可以测量肾上腺肿瘤患者提供的尿样中来自肾上腺的类固醇激素的排泄。初步结果表明，肾上腺良性肿瘤与恶性肾上腺肿瘤的类固醇激素排泄量有非常显著的差异。在这项提案中，我们将通过对大量肾上腺肿瘤患者的尿样进行前瞻性分析来验证该方法，该方法使用我们的测量技术，称为气相色谱/质谱仪(GC/MS)。测量结果将与数学家合作进行分析，数学家将帮助我们识别哪些激素最能让我们了解良性肿瘤和恶性肿瘤之间的区别。使用相关技术方法--液-质联用、LC/MS/MS？然后将用于类固醇的快速测量，这将有助于将我们的生物标记物工具整合到常规临床实践中。这项研究的患者招募将由包括欧洲肾上腺肿瘤研究网络(ENS@T)在内的国内和国际合作网络推动，这将确保我们可以在研究期间招募必要的患者数量。这项建议将来自不同学科的经验丰富的研究人员团队联系在一起，这将确保我们成功地改善肾上腺肿瘤患者的护理。

Adrenal tumours are common, affecting 1-2% of the general population. However, these tumours become more common with ageing and 3% of 40-year-olds and 10% of 70-year-olds have an adrenal tumour, many of them without knowing it. The majority of adrenal tumours are discovered incidentally, mostly following an imaging procedure like CT scanning arranged for other reasons than suspected adrenal disease. Once discovered, nodules in the adrenal need to be carefully evaluated as they may overproduce hormones with a potentially detrimental effect on health and, importantly, they could be malignant, either arising from the adrenal itself or representing metastases of other malignancies. Currently we use different imaging procedures and blood tests in the work-up of patients with adrenal tumours, but this is not always informative enough and it is often difficult to decide whether an adrenal tumour is benign or malignant. We have developed a biomarker tool that measures the excretion of steroid hormones deriving from the adrenal gland in urine samples provided by adrenal tumour patients. Preliminary results indicate that there are highly significant differences in steroid hormone excretion between benign and malignant adrenal tumours. In this proposal we will validate this method by the prospective analysis of a large number of urine samples from adrenal tumour patients by our measurement technique, called gas chromatography/mass spectrometry (GC/MS). Measurement results will be analyzed in collaboration with mathematicians who will help us to identify those hormones that will inform us best about the differences between benign and malignant tumours. Use of a related technology method - liquid chromatography/ mass spectrometry, LC/MS/MS ? will then be employed for the rapid measurement of steroids, which will help to integrate our biomarker tool into routine clinical practice. Patient recruitment to this study will be driven by national and international collaborative networks including the European Network for the Study of Adrenal Tumours (ENS@T), which will ensure that we can recruit the necessary patient number during the study lifetime. This proposal links a team of experienced researchers from different disciplines, which will ensure that we succeed in improving the care of patients with adrenal tumours.