Ultradian Steroid Rhythms in Adrenal Incidentalomas.

Overview

Twenty to 40% of adrenal incidentalomas are responsible for MACS (mild autonomous cortisol producing secretion). The biological tools used in current practice to explore MACS do not provide precise information on cortisol production abnormalities. This study is a comparative analysis of the dynamics/rhythmicity of interstitial cortisol and other steroid concentrations between MACS and non-secreting adenomas (ANS). Using the original and innovative U-RHYTHM system, interstitial fluid samples will be taken every 20 minutes for 24 to 48 hours from patients with MACS or non-secreting adenomas, and steroid assays will be performed in the perfusates to analyze steroid hormone production over 24 hours.

Adrenal incidentalomas are adrenal masses discovered incidentally during abdominal imaging. They are benign in the vast majority of cases, and most often non-secreting (non-secreting adenoma or ANS). In around 30% of cases, they are responsible for autonomous and moderately excessive cortisol secretion (MACS for "mild autonomous cortisol secretion"). MACS are associated with an increased prevalence of cardiovascular and metabolic comorbidities, and higher mortality than ANS. Beyond the quantitative cortisol production, that serves as a clock for biological rhythm of multiples organs (muscle, liver etc.), the integrity of the cortisol "nadir" (minimal levels around midnight) is fundamental from a metabolic perspective. As cortisol hypersecretion in MACS is moderate, it is suggested that its impact is linked to qualitative/temporal abnormalities in the secretion of cortisol and/or other related steroids. Only two studies (Debono, JCEM, 2017; Ceccato, Endocrine, 2018) suggest that excessive cortisol production in MACS may occur in the late afternoon or early evening. However, these studies are based on a small number of subjects and are hampered by the small number of blood or saliva samples, which are inappropriate to accurately assess the dynamics of daily cortisol secretion. In addition, these studies do not address the dynamics of other adrenal steroids that may play a role in the pathophysiology of MACS. The U-RHYTHMS sampling system is an original and innovative system for analyzing the dynamics of steroid hormone production over 24 hours. Using interstitial fluid samples taken every 20 min for 24 to 48 hours, in which hormone assays are performed, we will study the 24-hour steroid production dynamics in MACS and compare it with that of ANS. Apart from a pathophysiological interest, a better understanding of the abnormal dynamics of cortisol production could improve firstly the diagnostic of MACS with the identification of target periods to perform blood samples ; and, secondly, improve therapeutic management of patients with the identification of appropriate periods for the administration of short-acting steroidogenic drugs. Consent will be obtained at inclusion. The patient will be seen by the investigating physician twice, 27 hours apart, for insertion and removal of the U-RHYTHM system. Microdialysis samples will be collected in the collection system. Samples will be directly frozen at -20°C or -80°C and transported at -20°C to the Ultradian Analysis Laboratory, Metabolomics Centre, Department of Clinical Sciences, University of Bergen, Norway, for sample preparation, LC-MSMS steroid profiling (panel of 21 steroids) and statistical analysis. The research protocol does not include patient follow-up.