title: Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors.
abstract: BACKGROUND
  Adrenal tumors have a prevalence of around 2% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2-11% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values.
  
  
  OBJECTIVE
  Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy.
  
  
  METHODS
  Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19-84 yr) and 45 ACC patients (20-80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26-201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids.
  
  
  RESULTS
  Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88% (area under the curve = 0.96) when using only the nine most differentiating markers.
  
  
  CONCLUSIONS
  Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas.
authors.affiliation: Centre for Endocrinology, Diabetes, and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, United Kingdom. w.arlt@bham.ac.uk
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.forename: Michael
authors.initials: M
authors.lastname: Biehl
authors.forename: Angela E
authors.initials: AE
authors.lastname: Taylor
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.forename: Rossella
authors.initials: R
authors.lastname: Libé
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Hughes
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.forename: David J
authors.initials: DJ
authors.lastname: Smith
authors.forename: Han
authors.initials: H
authors.lastname: Stiekema
authors.forename: Nils
authors.initials: N
authors.lastname: Krone
authors.forename: Emilio
authors.initials: E
authors.lastname: Porfiri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Opocher
authors.forename: Jerôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Franco
authors.initials: F
authors.lastname: Mantero
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
authors.forename: Peter
authors.initials: P
authors.lastname: Nightingale
authors.forename: Cedric H L
authors.initials: CH
authors.lastname: Shackleton
authors.forename: Xavier
authors.initials: X
authors.lastname: Bertagna
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D000305:Adrenal Cortex Hormones / Q000652:urine*; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D018246:Adrenocortical Adenoma / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D018268:Adrenocortical Carcinoma / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D008875:Middle Aged
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers