Urine steroid metabolomics as a novel tool for detection of recurrent adrenocortical carcinoma
Open accessAbstract
CONTEXT: Urine steroid metabolomics, combining mass spectrometry-based steroid profiling and machine learning, has been described as a novel diagnostic tool for detection of adrenocortical carcinoma (ACC). OBJECTIVE, DESIGN, SETTING: This proof-of-concept study evaluated the performance of urine steroid metabolomics as a tool for postoperative recurrence detection after microscopically complete (R0) resection of ACC. PATIENTS AND METHODS: 135 patients from 14 clinical centers provided postoperative urine samples, which were analyzed by gas chromatography-mass spectrometry. We assessed the utility of these urine steroid profiles in detecting ACC recurrence, either when interpreted by expert clinicians or when analyzed by random forest, a machine learning-based classifier. Radiological recurrence detection served as the reference standard. RESULTS: Imaging detected recurrent disease in 42 of 135 patients; 32 had provided pre- and post-recurrence urine samples. 39 patients remained disease-free for ≥3 years. The urine "steroid fingerprint" at recurrence resembled that observed before R0 resection in the majority of cases. Review of longitudinally collected urine steroid profiles by 3 blinded experts detected recurrence by the time of radiological diagnosis in 50% to 72% of cases, improving to 69% to 92%, if a preoperative urine steroid result was available. Recurrence detection by steroid profiling preceded detection by imaging by more than 2 months in 22% to 39% of patients. Specificities varied considerably, ranging from 61% to 97%. The computational classifier detected ACC recurrence with superior accuracy (sensitivity = specificity = 81%). CONCLUSION: Urine steroid metabolomics is a promising tool for postoperative recurrence detection in ACC; availability of a preoperative urine considerably improves the ability to detect ACC recurrence.
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A recent study has shown utility of urinary steroid metabolomics in the follow up of patients with ACC as a marker of recurrence.
“A recent study has also shown the utility of urinary steroid metabolomics in the follow up of patients with ACC as a marker of recurrence (351).”
From Adrenal incidentaloma (2020) · cites this paper as [351]
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- Authors
- Chortis, V., Bancos, I., Nijman, T., Gilligan, L. C., Taylor, A. E., Ronchi, C. L., O’Reilly, M. W., Schreiner, J., Asia, M., Riester, A., Perotti, P., Libé, R., Quinkler, M., Canu, L., Paiva, I., Bugalho, M. J., Kastelan, D., Dennedy, M. C., Sherlock, M., Ambroziak, U., Vassiliadi, D., Bertherat, J., Beuschlein, F., Fassnacht, M., Deeks, J. J., Biehl, M., & Arlt, W.
- Affiliations
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Mayo Clinic (US)
- University of Groningen (NL)
- University of Birmingham (GB)
- University of Würzburg (DE)
- Ludwig-Maximilians-Universität München (DE)
- University of Turin (IT)
- INCa-COMETE, Cochin Hospital, Institut Cochin, Institut National de la Santé et de la Recherche Medicale Unite ́ 1016, René Descartes University, Paris
- Endocrinology in Charlottenburg, University of Berlin, Berlin, Germany
- University of Florence (IT)
- Unidade Local de Saúde de Coimbra (PT)
- Hospital de Santa Maria (PT)
- Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia
- Ollscoil na Gaillimhe – University of Galway (IE)
- Royal College of Surgeons in Ireland (IE)
- Medical University of Warsaw (PL)
- Evangelismos Hospital (GR)
- Inserm (FR)
- University of Zurich (CH)
- NIHR Birmingham Biomedical Research Centre (GB)
- Corresponding author
- Arlt, Wiebke
- ORCID
- Chortis, Vasileios
- Bancos, Irina
- Gilligan, Lorna C
- Taylor, Angela E
- Ronchi, Cristina L
- O’Reilly, Michael W
- Riester, Anna
- Quinkler, Marcus
- Canu, Letizia
- Paiva, Isabel
- Bugalho, Maria J
- Dennedy, M Conall
- Sherlock, Mark
- Ambroziak, Urszula
- Vassiliadi, Dimitra
- Bertherat, Jerome
- Beuschlein, Felix
- Fassnacht, Martin
- Deeks, Jonathan J
- Biehl, Michael
- Arlt, Wiebke
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2019-10-29
- Volume
- 105
- Issue
- 3
- Pages
- e307-e318
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC7112967
- OpenAlex
- W2982597248
- Cited by
- 93
- References
- 31
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 10 · 2023: 11 · 2022: 12 · 2021: 21 · 2020: 16
- FWCI
- 11.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion, cc-by)
- Florence Research (University of Florence) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Wellcome Trust (WT101671AIA)
- Deutsche Forschungsgemeinschaft (205/1)
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health (K23DK121888)
- National Institute for Health Research
- University Hospitals Birmingham NHS Foundation Trust
- University of Birmingham (BRC-1215–2009)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- adrenocortical carcinoma, recurrence detection, postoperative follow-up, R0 resection, random forest, early detection of recurrence
- MeSH terms
- Machine Learning, Proof of Concept Study, Adrenal Cortex, Adrenal Cortex Neoplasms, Adrenalectomy, Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Gas Chromatography-Mass Spectrometry, Middle Aged, Neoplasm Recurrence, Local, Postoperative Period, Retrospective Studies, Sensitivity and Specificity, Steroids, Tomography, X-Ray Computed, Biomarkers, Tumor, Adrenocortical Carcinoma, Metabolomics, Young Adult
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