TY  - JOUR
A1  - Arlt, Wiebke
A1  - Biehl, Michael
A1  - Taylor, Angela E.
A1  - Hahner, Stefanie
A1  - Libé, Rossella
A1  - Hughes, Beverly A.
A1  - Schneider, Petra
A1  - Smith, David J.
A1  - Stiekema, Han
A1  - Krone, Nils
A1  - Porfiri, Emilio
A1  - Opocher, Giuseppe
A1  - Bertherat, Jerôme
A1  - Mantero, Franco
A1  - Allolio, Bruno
A1  - Terzolo, Massimo
A1  - Nightingale, Peter
A1  - Shackleton, Cedric H. L.
A1  - Bertagna, Xavier
A1  - Fassnacht, Martin
A1  - Stewart, Paul M.
T1  - Urine Steroid Metabolomics as a Biomarker Tool for Detecting Malignancy in Adrenal Tumors
JF  - The Journal of Clinical Endocrinology & Metabolism
N2  - Context:
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.

Design:
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.
KW  - adrenal cortex hormones
KW  - urine
KW  - adrenal cortex neoplasms
KW  - mass spectrometry
KW  - metabolomics
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154682
VL  - 96
IS  - 12
SP  - 3775
EP  - 3784
ER  - 
TY  - JOUR
A1  - Canu, Letizia
A1  - Puglisi, Soraya
A1  - Berchialla, Paola
A1  - De Filpo, Giuseppina
A1  - Brignardello, Francesca
A1  - Schiavi, Francesca
A1  - Ferrara, Alfonso Massimiliano
A1  - Zovato, Stefania
A1  - Luconi, Michaela
A1  - Pia, Anna
A1  - Appetecchia, Marialuisa
A1  - Arvat, Emanuela
A1  - Letizia, Claudio
A1  - Maccario, Mauro
A1  - Parasiliti-Caprino, Mirko
A1  - Altieri, Barbara
A1  - Faggiano, Antongiulio
A1  - Modica, Roberta
A1  - Morelli, Valentina
A1  - Arosio, Maura
A1  - Verga, Uberta
A1  - Pellegrino, Micaela
A1  - Petramala, Luigi
A1  - Concistrè, Antonio
A1  - Razzore, Paola
A1  - Ercolino, Tonino
A1  - Rapizzi, Elena
A1  - Maggi, Mario
A1  - Stigliano, Antonio
A1  - Burrello, Jacopo
A1  - Terzolo, Massimo
A1  - Opocher, Giuseppe
A1  - Mannelli, Massimo
A1  - Reimondo, Giuseppe
T1  - A multicenter epidemiological study on second malignancy in non-syndromic pheochromocytoma/paraganglioma patients in Italy
JF  - Cancers
N2  - No studies have carried out an extensive analysis of the possible association between non-syndromic pheochromocytomas and paragangliomas (PPGLs) and other malignancies. To assess >the risk of additional malignancy in PPGL, we retrospectively evaluated 741 patients with PPGLs followed-up in twelve referral centers in Italy. Incidence of second malignant tumors was compared between this cohort and Italian patients with two subsequent malignancies. Among our patients, 95 (12.8%) developed a second malignant tumor, which were mainly prostate, colorectal and lung/bronchial cancers in males, breast cancer, differentiated thyroid cancer and melanoma in females. The standardized incidence ratio was 9.59 (95% CI 5.46–15.71) in males and 13.21 (95% CI 7.52–21.63) in females. At multivariable analysis, the risk of developing a second malignant tumor increased with age at diagnosis (HR 2.50, 95% CI 1.15–5.44, p = 0.021 for 50–59 vs. <50-year category; HR 3.46, 95% CI 1.67–7.15, p < 0.001 for >60- vs. <50-year). In patients with available genetic evaluation, a positive genetic test was inversely associated with the risk of developing a second tumor (HR 0.25, 95% CI 0.10–0.63, p = 0.003). In conclusion, PPGLs patients have higher incidence of additional malignant tumors compared to the general population who had a first malignancy, which could have an impact on the surveillance strategy.
KW  - pheochromocytoma
KW  - paraganglioma
KW  - epidemiology
KW  - genetic analysis
KW  - mortality
KW  - surveillance
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250148
SN  - 2072-6694
VL  - 13
IS  - 22
ER  -