MECHANISMS IN ENDOCRINOLOGY: Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional MRI studies.

Eur J Endocrinol. 2015 Feb 3;

Authors: Andela CD, Van Haalen F, Ragnarsson O, Papakokkinou E, Johannsson G, Santos A, Webb S, Biermasz NR, van der Wee NJ, Pereira AM

Abstract
Background: Cushing's syndrome is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids. Objective: To review publications evaluating brain characteristics in patients with Cushing's syndrome using magnetic resonance imaging (MRI). Methods: Systematic review of literature published in Pubmed, Embase, Web of Knowledge, and Cochrane databases. Results: Nineteen studies using MRI in patients with Cushing's syndrome were selected, including studies in patients with active disease, patients in long-term remission and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e. cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, triglyceride levels) and behavioral outcome (i.e. cognitive and emotional functioning, mood, and quality of life). Conclusion: Patients with active Cushing's syndrome demonstrate brain abnormalities, which only partly recover after biochemical cure, since these still occur even after long-term remission. Cushing's syndrome might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.

PMID: 25650405 [PubMed - as supplied by publisher]