ESPE2021 ePoster Category 1 Pituitary B (10 abstracts)
The Adrenal Steroid Profile in Adolescent Depression: A Valuable Bio-Readout?
Raphael Hirtz 1 , Lars Libuda 2 , Anke Hinney 3 , Manuel Föcker 4 , Bühlmeier Judith 3 , Paul-Martin Holterhus 5 , Alexandra Kulle 5 , Cordula Kiewert 1 , Berthold Hauffa 1 , Johannes Hebebrand 3 & Corinna Grasemann 6
1Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; 2Department of Exercise and Health, Institute of Nutrition, Consumption and Health, University of Paderborn, Paderborn, Germany; 3Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; 4Department of Child and Adolescent Psychiatry, University Hospital Münster, Münster, Germany; 5Department of Paediatrics I, Paediatric Endocrinology and Diabetes, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel, and Christian-Albrechts-University, Kiel, Germany; 6Department of Pediatrics, Division of Rare Diseases, St Josef-Hospital, and CeSER, Ruhr-University Bochum, Bochum, Germany
Background: There is preliminary evidence that adrenal steroids other than cortisol may be valuable biomarkers for major depressive disorder (MDD). So far, studies have been conducted in adults only, and conclusions are limited, mainly due to small sample sizes. Therefore, the present study was intended to assess whether adrenal steroids (progesterone, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, deoxycorticosterone, corticosterone) serve as biomarkers for adolescent MDD.
Methods: In 261 depressed adolescents (Nfemales = 170), treated at a single psychiatric hospital between 2016 and 2019, serum adrenal steroids were determined by liquid chromatography-tandem mass spectrometry. Findings were compared to that of an age- and sex-matched reference cohort (n = 255) by nonparametric analysis of variance. Nonparametric receiver operating characteristics (ROC) analyses were conducted to evaluate the diagnostic performance of single steroids and steroid ratios to classify depression status. Sensitivity analyses considered important confounders of adrenal functioning, and ROC results were additionally verified by cross-validation.
Results: Compared to the reference cohort, levels of deoxycorticosterone and 21-deoxycortisol were decreased (P < .001). All other glucocorticoid- and mineralocorticoid-related steroids were increased (P < .001). The corticosterone to deoxycorticosterone ratio evidenced excellent classification characteristics, especially in females (Area Under the Curve (AUC): 0.957; sensitivity: 0.902; specificity: 0.891).
Conclusion: The adrenal steroid metabolome qualifies as a bio-readout reflecting adolescent MDD by a distinct steroid pattern that indicates dysfunction of the hypothalamus-pituitary-adrenal axis. Moreover, the corticosterone to deoxycorticosterone ratio may prospectively qualify to contribute to precision medicine in psychiatry by identifying those patients who might benefit from antiglucocorticoid treatment or those at risk for recurrence when adrenal dysfunction has not resolved.
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