☆ 4.2 Review

Long-term effects of glucocorticoid excess on the brain

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Glucose and lipid metabolism abnormalities in Cushing's syndrome

Rezvan Salehidoost et al.

Summary: Prolonged excess of glucocorticoids can lead to metabolic alterations, including increased gluconeogenesis, reduced insulin sensitivity, inhibited insulin secretion, and increased fat tissue and free fatty acid levels. These metabolic changes can have negative impacts on health and mortality, highlighting the importance of long-term monitoring.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Editorial Material Endocrinology & Metabolism

Cushing's syndrome update: 100 years after Minnie G

Robert P. Millar et al.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Role of radiosurgery in the treatment of Cushing's disease

Marco Losa et al.

Summary: Radiotherapy, particularly Gamma Knife radiosurgery (GKRS), is a useful adjuvant treatment for patients with persistent or recurrent Cushing's disease. The most common side effect is hypopituitarism, while severe neurological complications are rare in radiation-naive patients.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Clinical presentation and etiology of Cushing's syndrome: Data from ERCUSYN

Elena Valassi

Summary: This study presents data on the clinical presentation at diagnosis in 1564 patients with Cushing's syndrome. The most frequent symptoms were weight gain, hypertension, skin alterations, and myopathy. Men were more likely to experience reduced libido and bone fractures, while women were more likely to have skin alterations and menstrual irregularities. Patients had poor quality of life at diagnosis, and there was a delay of 2 years between symptom onset and diagnosis. It is important to develop strategies to shorten the time to diagnosis and start treatment promptly to reduce the burden on patients' psychophysical health.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Long-term morbidity and mortality in patients with Cushing's syndrome

Leah T. Braun et al.

Summary: Patients with Cushing's syndrome have increased multisystem morbidity and mortality, presenting clinical problems such as hypertension, diabetes, overweight, and myopathy. Mortality is particularly high during active disease and within the first year after diagnosis.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Hypothalamic-pituitary-adrenal axis recovery after treatment of Cushing's syndrome

Annemarie Balasko et al.

Summary: Secondary adrenal insufficiency develops after successful treatment for Cushing's syndrome. Glucocorticoid replacement therapy is necessary until the recovery of the HPA axis. Patients often experience symptoms of glucocorticoid withdrawal syndrome after cure. Individualized treatment is needed to avoid overtreatment or undertreatment.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Distinguishing Cushing's disease from the ectopic ACTH syndrome: Needles in a haystack or hiding in plain sight?

Aimee R. Hayes et al.

Summary: In the context of ACTH-dependent Cushing's syndrome, ectopic ACTH secretion from a neuroendocrine tumour needs to be differentiated carefully from pituitary-dependent Cushing's syndrome, Cushing's disease, for optimal therapy. Diagnosis may be difficult as clinical and biochemical tests may overlap with Cushing's disease. Imaging is essential and should be interpreted considering both anatomical and functional imaging modalities.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Aggressive corticotroph tumors and carcinomas

Helene Lasolle et al.

Summary: Pituitary tumors are usually benign, but aggressive pituitary tumors and carcinomas are rare and challenging to treat, with high mortality rates. Most of these are corticotroph tumors, which have special prognoses. Current clinical, pathological, and molecular prognostic markers are limited, making early management difficult. Temozolomide is the first-line treatment, with immune checkpoint inhibitors as alternative options for temozolomide treatment failure.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

The diagnosis and management of Cushing's syndrome in pregnancy

Ross Hamblin et al.

Summary: Endogenous Cushing's syndrome (CS) is rarely encountered during pregnancy and the diagnosis is challenging. Conclusive recommendations or a standardized management approach for all patients with CS in pregnancy cannot be made due to the lack of comprehensive literature. Management decisions, including surgery, medical control, or conservative approach, should be highly individualized and consider various factors such as stage of gestation, tumor localization, severity of CS, maternal comorbidity, and patient choice.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Pituitary MRI in Cushing's disease - an update

Jean-Francois Bonneville et al.

Summary: Pituitary MRI is essential for the diagnosis of ACTH-dependent Cushing's syndrome, but its results can vary. The expertise of the neuroradiologist, the use of a Tesla 3.0 MRI, and the choice of sequences are important factors. T2 and 3D gradient echo sequences after gadolinium injection are the most informative and can detect most macro- and microadenomas. However, diagnosing picoadenomas (<3-4 mm) remains challenging.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Genetics of Cushing's disease

Julia Simon et al.

Summary: Corticotroph tumours are sporadic monoclonal neoplasms, with USP8 gene mutations found in around half of cases. TP53 and ATXR mutations may indicate transition to a more aggressive tumour phenotype. The role and importance of other genomic alterations remain to be elucidated.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Diagnostic workup of Cushing's syndrome

Maria Balomenaki et al.

Summary: Cushing's syndrome is a rare but detrimental endocrine disorder, and early diagnosis and prompt treatment are crucial. The diagnostic approach involves a stepwise process of screening, confirming the diagnosis, and establishing the etiology.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Medical management of Cushing's disease: When and how?

Frederic Castinetti

Summary: Transsphenoidal surgery is the first-line treatment for Cushing's disease, but medical treatment is also an option in certain cases, such as severe hypercortisolism, short-term treatment before surgery, long-term treatment after failed surgery, or while waiting for the full effect of radiation therapy. The approach to medical treatment varies depending on the severity of hypercortisolism, with a block and replace approach for severe cases and a titration approach for mild cases.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

The corticotroph cells from early development to tumorigenesis

Jacques Drouin

Summary: Cells acquire their identity and properties through a series of events and transcription factor regulation, which determine their unique gene expression program and epigenomic state. Studying these developmental processes is crucial for understanding the unique features of cell lineages and the mechanisms underlying disease.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Article Rheumatology

Brain white matter extracellular free-water increases are related to reduced neurocognitive function in systemic lupus erythematosus

Xing Qian et al.

Summary: Brain white matter microstructural changes and increased extracellular free water (FW) volume are observed in SLE patients. The increased extracellular FW is associated with reduced neurocognitive performance, particularly in sustained attention, and higher cumulative glucocorticoid dose.

RHEUMATOLOGY (2022)

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Editorial Material Endocrinology & Metabolism

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality

Richard N. Clayton

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Surgery and perioperative management of patients with Cushing's disease

Juergen Honegger et al.

Summary: Transsphenoidal surgery (TSS) is the preferred initial treatment for Cushing's disease (CD), with microscopic TSS and endoscopic TSS being the two available surgical techniques. Repeat TSS can achieve remission rates of over 70% for microadenomas. Early postoperative assessment of remission status and a steroid-sparing protocol are recommended for postoperative management. Prophylactic antithrombotic measures can significantly reduce the risk of postoperative thromboembolic events. Prevention or successful treatment of cortisol withdrawal syndrome remains a challenge. The development of functional imaging holds promise for improved preoperative detection of microadenomas. Intraoperative identification of microadenomas using specific fluorescent targeting is a promising future avenue.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Review Endocrinology & Metabolism

Long-term follow-up and predictors of recurrence of Cushing's disease

Laurence Guignat et al.

Summary: Transsphenoidal surgery is the first-line treatment for Cushing's disease, with a remission rate of 70%-80%. However, the long-term remission rate is lower due to recurrence. Postoperative corticotroph insufficiency and its duration have been found to be protective factors against recurrence. Long-term monitoring with clinical and hormonal investigations is advised after postoperative recovery of the hypothalamic-pituitary-adrenal axis.

JOURNAL OF NEUROENDOCRINOLOGY (2022)

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Article Clinical Neurology

Reversibility of impaired brain structures after transsphenoidal surgery in Cushing's disease: a longitudinal study based on an artificial intelligence-assisted tool

Bo Hou et al.

Summary: The study reveals widespread brain volume loss in active Cushing's disease patients, but significant improvement after TSS. Most brain regions in remitted CD patients showed full recovery, except for the frontal and temporal lobes. ACTH and serum cortisol changes were negatively correlated with brain volume recovery.

JOURNAL OF NEUROSURGERY (2021)

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Review Endocrinology & Metabolism

Neuropsychological Functioning in Patients with Cushing's Disease and Cushing's Syndrome

Sonja Siegel et al.

Summary: The literature suggests that patients with Cushing's disease exhibit neuropsychological impairment in all domains, with memory and visuo-spatial processing being the most consistently affected. Short-term and long-term remission of the disease shows significant improvement in neuropsychological function, but not all domains return to normal. More studies are needed to further understand neuropsychological function in patients with Cushing's disease.

EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES (2021)

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Review Endocrinology & Metabolism

Glucocorticoids and the Brain after Critical Illness

Alice R. Hill et al.

Summary: Treatment for critical illness often focuses on short-term physical recovery, but recent research suggests long-term risks of cognitive impairment and psychiatric disorders in survivors, potentially linked to glucocorticoid levels. Elevated glucocorticoids can cause structural changes in the hippocampus and prefrontal cortex, impacting memory and cognition in critical illness survivors.

ENDOCRINOLOGY (2021)

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Article Clinical Neurology

Disruption of Rich-Club Connectivity in Cushing Disease

Can-Xin Xu et al.

Summary: The study revealed that patients with active CD have disrupted rich-club organization, with significant improvement in rich-club connectivity to normal levels after TSS. This suggests that rich club may serve as a new indicator to assess outcomes of TSS and understand the impact of excessive cortisol on brain functional connectivity in CD patients.

WORLD NEUROSURGERY (2021)

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Article Endocrinology & Metabolism

Potential associations between immune signaling genes, deactivated microglia, and oligodendrocytes and cortical gray matter loss in patients with long-term remitted Cushing's disease

S. E. E. C. Bauduin et al.

Summary: In patients with Cushing's disease, aberrant gene expression in the ACC may be related to immune function, with underexpressed genes primarily enriched for deactivated microglia and oligodendrocytes. These findings suggest a protective role of these cell types against the long-term effects of cortisol overexposure.

PSYCHONEUROENDOCRINOLOGY (2021)

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Article Neurosciences

Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse

Jorge Miguel Amaya et al.

Summary: Chronic exposure to high levels of glucocorticoids can have detrimental effects on health, leading to metabolic abnormalities such as those seen in Cushing's syndrome. MRI studies have shown volumetric changes in the brains of CS patients, both during active disease and in remission. Research in the AdKO mouse model for CS revealed brain region-specific changes, including aberrant myelination and white matter damage.

FRONTIERS IN NEUROSCIENCE (2021)

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Article Medicine, General & Internal

The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone

Anne-Sophie C. A. M. Koning et al.

Summary: The study aims to reduce the neuropsychiatric adverse effects of dexamethasone treatment by reactivating the mineralocorticoid receptor using cortisol. It is a double-blind placebo-controlled trial evaluating patients' Brief Psychiatric Rating Scale scores postoperatively.

BMJ OPEN (2021)

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Review Cardiac & Cardiovascular Systems

Metabolic Syndrome and Cognitive Function

Mouna Tahmi et al.

Summary: Metabolic syndrome (MetS) is associated with lower cognitive function, particularly in cross-sectional studies. The impact of MetS on cognition varies depending on factors such as age and gender, making it an important predictor for cognitive function and cognitive impairment.

CURRENT CARDIOLOGY REPORTS (2021)

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Article Endocrinology & Metabolism

Trends in regional morphological changes in the brain after the resolution of hypercortisolism in Cushing's disease: a complex phenomenon, not mere partial reversibility

Hong Jiang et al.

Summary: This study investigated the regional volumetric alterations in Cushing's disease patients and found trends toward normalization in most brain substructures. However, different trends were observed in other subregions, such as the amygdala, thalamus, and caudate. The morphological changes in gray matter volumes after the resolution of hypercortisolism are complex and significantly differ within brain substructures.

ENDOCRINE CONNECTIONS (2021)

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Article Medicine, General & Internal

A Case of Cushing's Disease Presenting with Isolated Suicidal Attempt

Sultan Dheafallah Al-Harbi et al.

Summary: Cushing's disease is caused by abnormal secretion of ACTH from the pituitary, resulting in increased cortisol production from the adrenal glands. This can lead to a range of metabolic and psychiatric disturbances, with symptoms such as severe depression. Early diagnosis and management may help in reducing psychiatric symptoms, but the response of neuropsychiatric disorders after remission of Cushing syndrome is variable and necessitates long term follow-up.

CLINICAL MEDICINE INSIGHTS-CASE REPORTS (2021)

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Article Neuroimaging

Altered microstructural pattern of white matter in Cushing's disease identified by automated fiber quantification

Mengchu Cui et al.

Summary: The study demonstrates widespread alterations in white matter microstructure in patients with Cushing's disease induced by hypercortisolism, including increased diffusivity and decreased fractional anisotropy, with abnormalities localized to specific positions within certain fibers. These microstructural changes are associated with ACTH and cortisol concentration as well as cognitive decline in Cushing's disease patients, providing potential targets for early identification and intervention.

NEUROIMAGE-CLINICAL (2021)

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Article Neurosciences

Oral corticosteroid dosage and clinical presentation of psychiatric conditions after steroid use: A consultation-liaison psychiatry service's experience

Yuko Yagi et al.

Summary: The research aimed to determine the incidence and dose-dependency of psychiatric conditions in patients receiving corticosteroid treatment. Results showed no significant differences in patient background characteristics and the incidence of most psychiatric conditions between high-dose and low-dose groups, except for a higher incidence of delirium in the low-dose group.

NEUROPSYCHOPHARMACOLOGY REPORTS (2021)

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Review Endocrinology & Metabolism

Dynamics of ACTH and Cortisol Secretion and Implications for Disease

Stafford L. Lightman et al.

ENDOCRINE REVIEWS (2020)

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Psychiatric and neurocognitive consequences of endogenous hypercortisolism

M. Piasecka et al.

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Neuropsychological and Emotional Functioning in Patients with Cushing's Syndrome

Sabrina Na et al.

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Detrimental effects of hypercortisolism on brain structure and related risk factors

Yaxi Chen et al.

SCIENTIFIC REPORTS (2020)

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Cortical thickness abnormalities in long-term remitted Cushing's disease

S. E. E. C. Bauduin et al.

TRANSLATIONAL PSYCHIATRY (2020)

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Basolateral Amygdala Connectivity With Subgenual Anterior Cingulate Cortex Represents Enhanced Fear-Related Memory Encoding in Anxious Humans

Yuko Hakamata et al.

BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING (2020)

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Pharmacological stress impairs working memory performance and attenuates dorsolateral prefrontal cortex glutamate modulation

Eric A. Woodcock et al.

NEUROIMAGE (2019)

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Review Psychology, Clinical

Corticosteroids and Cognition: A Meta-Analysis

Catherine E. Prado et al.

NEUROPSYCHOLOGY REVIEW (2019)

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Article Endocrinology & Metabolism

Hippocampal Volume, Cognitive Functions, Depression, Anxiety, and Quality of Life in Patients With Cushing Syndrome

Katrine Emilie Frimodt-Moller et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2019)

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A randomized trial of an NMDA receptor antagonist for reversing corticosteroid effects on the human hippocampus

E. Sherwood Brown et al.

NEUROPSYCHOPHARMACOLOGY (2019)

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Glucocorticoid-Induced Reductions of Myelination and Connexin 43 in Mixed Central Nervous System Cell Cultures Are Prevented by Mifepristone

Jose Javier Miguel-Hidalgo et al.

NEUROSCIENCE (2019)

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Late glucocorticoid receptor antagonism changes the outcome of adult life stress

Jinlan Ding et al.

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Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

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White matter involvement on DTI-MRI in Cushing's syndrome relates to mood disturbances and processing speed: a case-control study

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PLOS ONE (2017)

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Brain metabolite abnormalities in ventromedial prefrontal cortex are related to duration of hypercortisolism and anxiety in patients with Cushing's syndrome

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Hippocampal Volume in Healthy Controls Given 3-Day Stress Doses of Hydrocortisone

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Widespread reductions of white matter integrity in patients with long-term remission of Cushing's disease

Steven J. A. van der Werff et al.

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Hippocampal dysfunction in cured Cushing's syndrome patients, detected by 1H-MR-spectroscopy

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Long-Term Cognitive Impairments and Attentional Deficits in Patients with Cushing's Disease and Cortisol-Producing Adrenal Adenoma in Remission

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Chronic Stress Causes Frontostriatal Reorganization and Affects Decision-Making

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Joel C. Geerling et al.

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Amygdala volume in patients receiving chronic corticosteroid therapy

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Studies of hormone action in the hippocampal formation -: Possible relevance to depression and diabetes

BS McEwen et al.

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