Long-Term Cognitive Impairments and Attentional Deficits in Patients with Cushing's Disease and Cortisol-Producing Adrenal Adenoma in Remission
Department of Endocrinology, Gröna Stråket 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. .The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 07/2012; 97(9):E1640-8. DOI: 10.1210/jc.2012-1945
Context: Cognitive function is impaired in patients with active Cushing's syndrome (CS). Objective: The aim was to study cognitive function in patients with CS in long-term remission. Design: We conducted a cross-sectional, case-controlled, single center study. Patients: Fifty-five patients previously treated for Cushing's disease (n = 43) and cortisol-producing adrenal adenoma (n = 12) and 55 controls matched for age, gender, and educational level participated in the study. Methods: Working memory, attention, information-processing speed, verbal fluency, and reading speed were studied using standardized neuropsychological testing and alerting, orienting, and executive control using the Attentional Network Test. Fatigue impact scale and the comprehensive psychopathological rating scale were used to evaluate fatigue and affective disorder. Results: Median (interquartile range) duration of remission was 13 (5-19) yr and the mean ± sd age at follow-up was 54 ± 14 yr. Compared to controls, patients had a higher score on the fatigue impact scale, indicating greater burdens of fatigue, and a higher score on the comprehensive psychopathological rating scale subscales for depression and anxiety. In a multivariate analysis, attention, spatial orienting, alerting, working memory, verbal fluency, and reading speed were all diminished in comparison to controls, independent of scores for affective disorder and fatigue. No overall difference in outcome was seen between patients in long-term remission for Cushing's disease and cortisol-producing adrenal adenoma. Conclusion: Patients with CS in remission have impaired cognitive function that cannot be explained by the coexistence of affective disorder or chronic fatigue. The pattern of cognitive and attentional deficits suggests a more global involvement of the brain function than has previously been suggested.
Article: Fatigue Is the Best PillowChest 06/2013; 143(6):1523-5. DOI:10.1378/chest.13-0508 · 7.48 Impact Factor
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ABSTRACT: OBJECTIVE: Patients with Cushing's syndrome (CS) in long-term remission have impaired cognitive function. Cerebrospinal fluid (CSF) biomarkers are important diagnostic tools in the work-up of patients with cognitive impairment. The aim of this study was to analyze neurodegenerative and inflammatory biomarkers in CSF from patients with CS in remission. DESIGN: A cross-sectional, single centre study. PATIENTS: Twelve women previously treated for CS and six healthy subjects. MEASUREMENTS: Neurodegenerative CSF markers; total tau, hyperphosphorylated tau, amyloid beta peptides, soluble amyloid precursor protein alpha and beta, neurofilament light proteins, glial fibrillary acidic protein and monocyte chemoattractant protein 1, and inflammatory CSF markers; interferon-gamma, Interleukin (IL)-1B, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13 and tumour necrosis factor alpha. RESULTS: The mean age (mean ± SD) was similar in patients with CS in remission (44.9 ± 14 years) and healthy subjects (42.3 ± 15.7 years; P = 0.726). No differences were seen in concentrations of any neurodegenerative biomarkers between patients and healthy subjects. Nor was the concentration of inflammatory biomarkers different between the groups. CONCLUSIONS: The pattern of neurodegenerative and inflammatory biomarkers in CSF from patients with CS in remission does not differ from healthy subjects. The underlying mechanisms of the cognitive deficits in CS in remission are different from those seen in neurodegenerative disorders and remains to be explained.European Journal of Endocrinology 06/2013; 169(2). DOI:10.1530/EJE-13-0205 · 4.07 Impact Factor
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ABSTRACT: One-hundred years have passed since Harvey Williams Cushing presented the first patient with the syndrome that bears his name. In patients with Cushing's syndrome body composition, lipid-, carbohydrate- and protein-metabolism is dramatically affected and psychopathology and cognitive dysfunction is frequently observed. Untreated patients with Cushing's syndrome have a grave prognosis with an estimated five-year survival of only 50%. Remission can be achieved by surgery, radiotherapy and sometimes with medical therapy. Recent data indicate that the adverse metabolic consequences of Cushing's syndrome are present for years after successful treatment. In addition, recent studies have demonstrated that health related quality of life and cognitive function is impaired in patients with Cushing's syndrome in long-term remission. The focus of specialized care should therefore not only be on the diagnostic work-up and the early post-operative management, but also the long-term follow-up. In this paper we review the long-term consequences in patients with Cushing's syndrome in remission with focus on the neuropsychological effects and discuss the importance of these findings for long-term management. We also discuss three different phases in the postoperative management of surgically treated patients with Cushing's syndrome, each phase distinguished by specific challenges; the immediate post-operative phase, the glucocorticoid dose tapering phase and the long-term management. The focus of the long-term specialized care should be to identify cognitive impairments and psychiatric disorders, evaluate cardiovascular risk, follow pituitary function and to detect possible recurrence of Cushing's syndrome.European Journal of Endocrinology 08/2013; 169(5). DOI:10.1530/EJE-13-0534 · 4.07 Impact Factor
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