This thesis aims to further unravel the role of the stress-systems in the pathophysiology of stress-related psychiatric disorders, by exploring elements of regulation and dysregulation of the two... Show moreThis thesis aims to further unravel the role of the stress-systems in the pathophysiology of stress-related psychiatric disorders, by exploring elements of regulation and dysregulation of the two major stress systems (i.e. the ANS and the HPA-axis), and their relation with psychological and psychiatric characteristics. Show less
Cushing's syndrome is a rare disease with an endogenous cause of excess cortisol secretion. More evidence substantially links cortisol levels to the pachychoroid spectrum diseases. In this... Show moreCushing's syndrome is a rare disease with an endogenous cause of excess cortisol secretion. More evidence substantially links cortisol levels to the pachychoroid spectrum diseases. In this systematic review and meta-analysis, we summarize available evidence on pachychoroid spectrum diseases in patients with Cushing's syndrome. We performed a systematic literature search in 11 databases on 21 May 2022. Studies were considered eligible if they performed retinal examination of a consecutive group of patients with Cushing's syndrome using optical coherence tomography (OCT) scans. We extracted data on subfoveal choroidal thickness in patients with Cushing's syndrome compared to matched controls. We also extracted data on the prevalence of pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and polypoidal choroidal vasculopathy (PCV). We identified six eligible studies with a total of 159 patients with Cushing's syndrome. On average, patients with Cushing's syndrome have 49.5 mu m thicker subfoveal choroidal thickness compared to matched healthy individuals. Pachychoroid spectrum diseases were relatively common in these patients: PPE in 20.8%, CSC in 7.7%, and PCV in 2.8%. We conclude that there should be low threshold to recommend ophthalmic examination to patients with Cushing's syndrome, and that a macular OCT is recommended during this examination. Show less
Bauduin, S.E.E.C.; Rooijen, I.L.B. den; Meijer, M.; Werff, S.J.A. van der; Keo, A.; Dzyubachyk, O.; ... ; Mahfouz, A. 2021
Introduction: Cushing's disease (CD) is a rare and severe endocrine disease characterized by hypercortisolemia. Previous studies have found structural brain alterations in remitted CD patients... Show moreIntroduction: Cushing's disease (CD) is a rare and severe endocrine disease characterized by hypercortisolemia. Previous studies have found structural brain alterations in remitted CD patients compared to healthy controls, specifically in the anterior cingulate cortex (ACC). However, potential mechanisms through which these persistent alterations may have occurred are currently unknown. Methods: Structural 3T MRI's from 25 remitted CD patients were linked with gene expression data from neurotypical donors, derived from the Allen Human Brain Atlas. Differences in gene expression between the ACC and an unaffected control cortical region were examined, followed by a Gene Ontology (GO) enrichment analysis. A cell type enrichment analysis was conducted on the differentially expressed genes, and a disease association enrichment analysis was conducted to determine possible associations between differentially expressed genes and specific diseases. Subsequently, cortisol sensitivity of these genes in existing datasets was examined. Results: The gene expression analysis identified 300 differentially expressed genes in the ACC compared to the cortical control region. GO analyses found underexpressed genes to represent immune function. The cell type specificity analysis indicated that underexpressed genes were enriched for deactivated microglia and oligodendrocytes. Neither significant associations with diseases, nor evidence of cortisol sensitivity with the differentially expressed genes were found. Discussion: Underexpressed genes in the ACC, the area vulnerable to permanent changes in remitted CD patients, were often associated with immune functioning. The specific lack of deactivated microglia and oligodendrocytes implicates protective effects of these cell types against the long-term effects of cortisol overexposure. Show less
Hypercortisolism causes numerous and potentially severe complications, which are often underestimated and not well recognized in clinical practice. There are two main causes for... Show moreHypercortisolism causes numerous and potentially severe complications, which are often underestimated and not well recognized in clinical practice. There are two main causes for hypercortisolism. Firstly, exogenous hypercortisolism through corticosteroid use, which is highly prevalent, since around 1% of the general population uses corticosteroids. Secondly, endogenous Cushing’s syndrome, which is rare, but the disease burden is considerable through increased morbidity and mortality risks. In this thesis, potential complications of exogenous hypercortisolism, and treatment and clinical outcomes of Cushing’s syndrome, are discussed. These studies on various aspects of hypercortisolism emphasize the importance of suppressing cortisol secretion to physiological ranges. Both hypercortisolism and adrenal insufficiency have enormous, and sometimes deleterious, impact on physical and psychological functioning. Treatment of hypercortisolism and adrenal insufficiency attempting to restore normal cortisol concentrations does not eliminate risk of adverse outcomes. Finally, increasing knowledge on the effects of endogenous Cushing’s syndrome and exogenous hypercortisolism is likely to improve patient care beyond the endocrinology department, as these conditions serve as a model for long-term exposure to stress, which is a highly prevalent condition. Insight into the potential consequences of long-term stress exposure, can aid all individuals exposed to long-term stress, including patients with chronic disease or long-term hospital admission. Show less
Background: Sex differences in clinical picture of ACTH-dependent Cushing's syndrome are controversial, except for the known higher prevalence in females. We compared a broad range of potential... Show moreBackground: Sex differences in clinical picture of ACTH-dependent Cushing's syndrome are controversial, except for the known higher prevalence in females. We compared a broad range of potential differences to enable a more accurate understanding of the clinical picture of sex-specific ACTH-dependent Cushing's syndrome.Methods: Cohort study including consecutive patients with ACTH-dependent Cushing's syndrome from Leiden and Berlin diagnosed between 2000 and 2016. We compared clinical presentation, biochemical parameters, diagnostic tests, surgical outcome, and comorbidities between men and women.Results: We included 130 patients: 37 males and 93 females. With similar cortisol concentrations, ACTH concentrations were higher in males than females at time of diagnosis (median: 116 vs. 57 ng/L). The prevalence of osteoporosis was higher in males than in females (48.6 vs. 25.0%), persisting after surgery, with more vertebral fractures (16.2 vs. 5.4%) before surgery. Males showed more anemia (75.9 vs. 36.8%) after surgery. There were no differences in etiology, pituitary tumor size, diagnostic and therapeutic strategy, or surgical outcome between sexes.Conclusions: Based on this study, males and females with ACTH-dependent Cushing's syndrome present different clinical patterns. However, these differences do not justify different diagnostic strategies or treatment based on sex, considering the similar surgical outcome. Clinicians should be alert to diagnose accompanying osteoporosis (with fractures) in male patients with ACTH-dependent Cushing's syndrome. Show less
The human body is inherently designed to be able to adapt to challenging situations. However, some experiences are so severe that they can lead to substantial and longerlasting disturbances in an... Show moreThe human body is inherently designed to be able to adapt to challenging situations. However, some experiences are so severe that they can lead to substantial and longerlasting disturbances in an individuals’ behavioral, psychological and physiological functioning. Importantly, there is a degree of inter-individual variation, as not all individuals show similar reactions to severe stress. Neuroimaging techniques can help to unravel the brain characteristics related to vulnerability and resilience to severe stress. In the research for this dissertation several neuroimaging modalities were used to further explore the brain characteristics related to (dys)function after exposure to severe stress and after exposure to hypercortisolism, such as voxel-based morphometry and diffusion tensor imaging to study the structure of gray and white matter in the brain, and resting-state fMRI to study functional connectivity patterns. We studied brain characteristics in several groups consisting of: patients in long-term remission of Cushing’s disease, and individuals with a history of childhood emotional maltreatment to examine the effects of hypercortisolism and severe stress on the brain. In addition, we studied a group of police officers and a group of individuals with a history of childhood maltreatment to investigate the brain characteristics related to resilience to stress. Show less
Conclusions The LBNQ-Pituitary can be used to assess the degree to which patients are bothered by the consequences of the pituitary disease, as well as their needs for support. It could also... Show moreConclusions The LBNQ-Pituitary can be used to assess the degree to which patients are bothered by the consequences of the pituitary disease, as well as their needs for support. It could also facilitate an efficient assessment of patients' needs for support in clinical practice. We postulate that paying attention to needs for support will lead to optimal patient care (e.g., improvement in psychosocial care), and positively affect QoL. Show less
Nowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing__s disease,... Show moreNowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing__s disease, Cushing__s syndrome or acromegaly, doctors should be aware of subtle cognitive impairments and the increased prevalence of psychopathology and maladaptive personality traits after long-term remission. In addition, these patients use ineffective coping strategies and have negative illness perceptions that are not always correct. Patients are labeled __cured__, but still experience chronic and persisting impairments due to their pituitary disease. Doctors should consider informing patients better about the long-term consequences and act as a guide in this __acceptance process__ of the patient. In addition, a multi-disciplinary team of endocrinologists, psychologists, and community health workers might also help patients in accepting and dealing with the consequences of their pituitary disease. Show less
