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Onno C Meijer and Alberto M Pereira

A comprehensive study from Denmark established that the systemic use of glucocorticoids hormones has an annual prevalence of 3% and has been stable from 1999 to 2014. We comment on the risk of potentially long-lasting adverse effects, dependent on glucocorticoid receptor overactivation, but also mineralocorticoid receptor under-activation. We discuss the potential effects of glucocorticoid use on efficacy and toxicity of other drugs that are frequently taken concomitantly. We discuss the potential alternatives such as more selective targeting, and novel types of glucocorticoid receptor ligands. We conclude that pending improved therapies more conservative prescription of glucocorticoids may be warranted in clinical practice.

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Cornelie D Andela, Steven J A van der Werff, J Nienke Pannekoek, Susan M van den Berg, Onno C Meijer, Mark A van Buchem, Serge A R B Rombouts, Roos C van der Mast, Johannes A Romijn, Jitske Tiemensma, Nienke R Biermasz, Nic J A van der Wee and Alberto M Pereira


Patients with long-term remission of Cushing's disease (CD) have persistent psychological and cognitive impairments. It is unknown whether, and to what extent, these impairments are accompanied by structural abnormalities in the brain. We aim to investigate structural changes in the brain in patients with predominantly long-term remission of CD and to examine whether these changes are associated with psychological and cognitive dysfunction and clinical severity.


A cross-sectional, case–control study.


In 25 patients with predominantly long-term remission of CD and 25 matched healthy controls, grey matter volumes in the regions of interest (hippocampus, amygdala, and anterior cingulate cortex (ACC)) and in the whole brain were examined, using 3T magnetic resonance imaging and a voxel-based morphometry approach. Psychological and cognitive functioning were assessed using validated questionnaires and clinical severity was assessed using the Cushing's syndrome severity index.


Compared with controls, patients had smaller grey matter volumes of areas in the ACC (on average 14%, P<0.05) and greater volume of the left posterior lobe of the cerebellum (on average 34%, P<0.05). As expected, patients with remitted CD reported more depressive symptoms (P=0.005), more anxiety (P=0.003), more social phobia (P=0.034), more apathy (P=0.002), and more cognitive failure (P=0.023) compared with controls, but the differences in grey matter volumes were not associated with psychological or cognitive measures, nor with clinical severity.


Patients with predominantly long-term remission of CD showed specific structural brain abnormalities, in the presence of psychological dysfunction. Our data form a basis for future work aimed at elucidating the relation of the structural brain abnormalities and the sustained psychological deficits after long-term exposure to high cortisol levels.