MECHANISMS IN ENDOCRINOLOGY: Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies
- 1 July 2015
- journal article
- research article
- Published by Oxford University Press (OUP) in Acta Endocrinologica
- Vol. 173 (1), R1-R14
- https://doi.org/10.1530/eje-14-1101
Abstract
Background: Cushing's syndrome (CS) 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 CS 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 CS 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, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life).Conclusion: Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.Keywords
This publication has 47 references indexed in Scilit:
- Multisystem Morbidity and Mortality in Cushing's Syndrome: A Cohort StudyJournal of Clinical Endocrinology & Metabolism, 2013
- Subtle Cognitive Impairments in Patients with Long-Term Cure of Cushing’s DiseaseJournal of Clinical Endocrinology & Metabolism, 2010
- Mortality in Patients Treated for Cushing’s Disease Is Increased, Compared with Patients Treated for Nonfunctioning Pituitary MacroadenomaJournal of Clinical Endocrinology & Metabolism, 2007
- Cushing's syndromeThe Lancet, 2006
- Quality of Life in Patients after Long-Term Biochemical Cure of Cushing’s DiseaseJournal of Clinical Endocrinology & Metabolism, 2005
- Persistence of Increased Cardiovascular Risk in Patients with Cushing's Disease after Five Years of Successful CureJournal of Clinical Endocrinology & Metabolism, 1999
- Cognitive dysfunction in patients treated for pituitary tumoursJournal of Clinical and Experimental Neuropsychology, 1997
- Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndromeBiological Psychiatry, 1992
- High Incidence of Cortical Atrophy of the Cerebral and Cerebellar Hemispheres in Cushing's DiseaseRadiology, 1971
- NEUROPSYCHIATRIC ASPECTS OF CUSHING'S SYNDROMEArchives of Neurology & Psychiatry, 1952