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  - Weigand, Isabel
A1  - Ronchi, Cristina L.
A1  - Rizk-Rabin, Marthe
A1  - Dalmazi, Guido Di
A1  - Wild, Vanessa
A1  - Bathon, Kerstin
A1  - Rubin, Beatrice
A1  - Calebiro, Davide
A1  - Beuschlein, Felix
A1  - Bertherat, Jérôme
A1  - Fassnacht, Martin
A1  - Sbiera, Silviu
T1  - Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas
JF  - Scientific Reports
N2  - Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30-40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion.
KW  - kinases
KW  - immunohistochemistry
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157952
VL  - 7
IS  - 49
ER  -