Metabolomic Biomarkers in Urine of Cushing's Syndrome Patients.
Cushing's syndrome (CS) is a disease which results from excessive levels of cortisol in the human body. The disorder is associated with various signs and symptoms which are also common for the general population not suffering from compound hypersecretion. Thus, more sensitive and selective methods are required for the diagnosis of CS. This follow-up study was conducted to determine which steroid metabolites could serve as potential indicators of CS and possible subclinical hypercortisolism in patients diagnosed with so called non-functioning adrenal incidentalomas (AIs). Urine samples from negative controls (n= 37), patients with CS characterized by hypercortisolism and excluding iatrogenic CS (n= 16), and patients with non-functioning AIs with possible subclinical Cushing's syndrome (n= 25) were analyzed using gas chromatography-mass spectrometry (GC/MS) and gas chromatograph equipped with flame ionization detector (GC/FID). Statistical and multivariate methods were applied to investigate the profile differences between examined individuals. The analyses revealed hormonal differences between patients with CS and the rest of examined individuals. The concentrations of selected metabolites of cortisol, androgens, and pregnenetriol were elevated whereas the levels of tetrahydrocortisone were decreased for CS when opposed to the rest of the study population. Moreover, after analysis of potential confounding factors, it was also possible to distinguish six steroid hormones which discriminated CS patients from other study subjects. The obtained discriminant functions enabled classification of CS patients and AI group characterized by mild hypersecretion of cortisol metabolites. It can be concluded that steroid hormones selected by applying urinary profiling may serve the role of potential biomarkers of CS and can aid in its early diagnosis.
Department of Food Sciences, Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. kotlowska@gumed.edu.pl.
Alicja
A
Kotłowska
Laboratory of Environmental Chemometrics, Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland. t.puzyn@qsar.eu.org.
Tomasz
T
Puzyn
Department of Endocrinology and Internal Medicine, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland. ksworczak@gumed.edu.pl.
Krzysztof
K
Sworczak
Department ofEnvironmental Analytics,Institute for Environmental and Human Health Protection, Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland. piotr.stepnowski@ug.edu.pl.
Piotr
P
Stepnowski
Department of Food Sciences, Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. pszef@gumed.edu.pl.
Piotr
P
Szefer
D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D016000:Cluster Analysis; D003480:Cushing Syndrome / Q000378:metabolism* / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization
D015415:Biomarkers
Cushing’s syndrome; biomarkers; gas chromatography; linear discriminant analysis; metabolomics; multivariate analysis; steroid hormones; urinary profiling