Small cerebellar cortex volume in patients with active Cushing's syndrome

Santos, Alicia; Resmini, Eugenia; Crespo, Iris; Pires, Patrício José Moreira; Vives-Gilabert, Yolanda; Granell, Enric Marco; Valassi, Elena; Gómez‐Anson, Beatriz; Martínez-Momblán, Ma Antonia; Mataró, María; Webb, Susan M.

doi:10.1530/eje-14-0371

Cited by 56 publications

(61 citation statements)

References 45 publications

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“…In agreement, Bourdeau et al (15) demonstrated that patients with active CS had increased third ventricle diameter, bicaudate diameter, and cerebral atrophy, compared with control patients with no sellar tumors. A recent study has found smaller grey matter volumes of the bilateral cerebellum in patients with active CS compared with controls (19). When investigating the effect of CS on the developing brain, children with CS were found to have smaller cerebral volumes, larger ventricles and smaller amygdala than controls (27).…”

Section: Mri Outcome In Patients With Active Csmentioning

confidence: 91%

“…Review C D Andela and others MRI studies in Cushing's syndrome criteria, but mentioned criteria of remission (15,16,17,18,19). One study did neither describe diagnostic nor remission criteria (20).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

“…Described remission criteria were normal UFC (15,16,17,18,19), adrenal insufficiency, morning cortisol suppression after low dose dexamethasone overnight (1 mg) (17,18,19), or !30 mg hydrocortisone/day (15).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

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

Andela

Haalen

Ragnarsson

et al. 2015

European Journal of Endocrinology

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147

129

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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.

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Section: Mri Outcome In Patients With Active Csmentioning

confidence: 91%

Section: European Journal Of Endocrinologymentioning

confidence: 99%

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

Andela

Haalen

Ragnarsson

et al. 2015

European Journal of Endocrinology

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147

129

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“…Depression, anxiety and cognitive dysfunction are common in CS, especially in the active phase, although the so-called 'cured' patients still complain of a lower general well-being, more anxiety and depression, and impaired QoL when compared to matched healthy controls (49,56,57,58). Furthermore, after successful treatment, it often takes several months or even more than 1 year to perceive improvements.…”

Section: Cushing's Diseasementioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Quality of life tools for the management of pituitary disease

Webb

Crespo

Santos

et al. 2017

European Journal of Endocrinology

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Background: In the last few years, quality of life (QoL) has become an outcome measure in patients with pituitary diseases. Objective: To describe the available data on QoL impairment evaluated with questionnaires in patients with pituitary diseases. Design: Critical review of the pertinent literature and pragmatic discussion of available information. Methods: Selection of relevant literature from PubMed and WOK, especially from the last 5 years and comprehensive analysis. Results: QoL is impaired in all pituitary diseases, mostly in acromegaly and Cushing's disease (similar to other causes of Cushing's syndrome), but also in non-functioning pituitary adenomas and prolactinomas, especially in the active phase of the disease. Nevertheless, even after endocrine 'cure', scores tend to be below normative values, indicative of residual morbidity after hormonal control. The presence of hypopituitarism worsens subjective QoL perception, which can improve after optimal substitution therapy, including recombinant human growth hormone, when indicated. Conclusions: To improve the long-term outcome of pituitary patients, helping them to attain the best possible health, it appears desirable to include subjective aspects captured when evaluating QoL, so that the affected dimensions are identified and if relevant treated. Additionally, being aware that treatment outcome may not always mean complete normalisation of physical and mental issues related to QoL can be a first step to adaptation and conforming to this new status.

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“…10,13,25 Another region of potential reduction of volume is the cerebellum, which is prone to atrophic degeneration in long-term hypercortisolism. 28,31 Most studies regarding brain atrophy in CD or Cushing's syndrome (CS) are based on subjective evaluation of MR images and manual measurements of different regions of interest. 6,32,34 Studies based on objective, voxelbased measurements of brain atrophy in CD are very rare and have dealt with patients in long-term remission from CD.…”

mentioning

confidence: 99%

Hippocampal and cerebellar atrophy in patients with Cushing’s disease

Burkhardt¹,

Lüdecke

Spies

et al. 2015

FOC

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OBJECT Cushing’s disease (CD) may cause atrophy of different regions of the human brain, mostly affecting the hippocampus and the cerebellum. This study evaluates the use of 3-T MRI of newly diagnosed patients with CD to detect atrophic degeneration with voxel-based volumetry. METHODS Subjects with newly diagnosed, untreated CD were included and underwent 3-T MRI. Images were analyzed using a voxelwise statistical test to detect reduction of brain parenchyma. In addition, an atlas-based volumetric study for regions likely to be affected by CD was performed. RESULTS Nineteen patients with a mean disease duration of 24 months were included. Tumor markers included adre-nocorticotropic hormone (median 17.5 pmol/L), cortisol (949.4 nmol/L), and dehydroepiandrosterone sulfate (5.4 μmol/L). The following values are expressed as the mean ± SD. The voxelwise statistical test revealed clusters of significantly reduced gray matter in the hippocampus and cerebellum, with volumes of 2.90 ± 0.26 ml (right hippocampus), 2.89 ± 0.28 ml (left hippocampus), 41.95 ± 4.67 ml (right cerebellar hemisphere), and 42.11 ± 4.59 ml (left cerebellar hemisphere). Healthy control volunteers showed volumes of 3.22 ± 0.25 ml for the right hippocampus, 3.23 ± 0.25 ml for the left hippocampus, 50.87 ± 4.23 ml for the right cerebellar hemisphere, and 50.42 ± 3.97 ml for the left cerebellar hemisphere. CONCLUSIONS Patients with untreated CD show significant reduction of gray matter in the cerebellum and hippocampus. These changes can be analyzed and objectified with the quantitative voxel-based method described in this study.

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Small cerebellar cortex volume in patients with active Cushing's syndrome

Abstract: The cerebellar cortex volume is smaller in active CS patients than in controls. This finding is associated with poor visual memory and quality of life and is mostly pronounced in patients with higher triglyceride levels and older age at diagnosis.

Cited by 56 publications

References 45 publications

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

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

MANAGEMENT OF ENDOCRINE DISEASE: Quality of life tools for the management of pituitary disease

Hippocampal and cerebellar atrophy in patients with Cushing’s disease

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