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

肾上腺肿瘤很常见，影响总人口的1-2%。然而，随着年龄的增长，这些肿瘤变得越来越普遍，40岁的人中有3%患有肾上腺瘤，70岁的人中有10%患有肾上腺瘤，其中许多人并不知情。大多数肾上腺肿瘤是偶然发现的，大多数是由于其他原因而不是疑似肾上腺疾病而安排的CT扫描等成像程序。一旦发现，肾上腺结节需要仔细评估，因为它们可能产生过多的激素，对健康有潜在的有害影响，重要的是，它们可能是恶性的，要么是由肾上腺本身引起的，要么是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检查，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。我们开发了一种生物标志物工具，用于测量肾上腺肿瘤患者提供的尿液样本中肾上腺类固醇激素的排泄。初步结果表明，肾上腺良性肿瘤和恶性肿瘤在类固醇激素分泌方面存在显著差异。在这个提议中，我们将通过我们的测量技术，称为气相色谱/质谱（GC/MS），对肾上腺肿瘤患者的大量尿液样本进行前瞻性分析来验证该方法。测量结果将与数学家合作进行分析，他们将帮助我们识别那些将最好地告知我们良性和恶性肿瘤之间差异的激素。使用相关的技术方法-液相色谱/质谱，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志物工具整合到常规临床实践中。本研究的患者招募将由国家和国际合作网络推动，包括欧洲肾上腺肿瘤研究网络（ENS@T），这将确保我们能够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起来，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.