Development and validation of the disease-specific QOL-CD quality of life questionnaire for patients with Cushing's disease.

OBJECTIVE: Cushing's disease (CD) patients experience a range of debilitating symptoms that impair quality of life (QOL) as assessed using generic measures. These generic measures are inadequate to capture the disease-specific burden of illness. The development of the CD-specific QOL-CD measure of QOL using items generated by CD patients and healthcare professionals will provide a holistic assessment of patient outcomes and efficacy of novel therapies. METHODS: A total of 96 CD patients participated. A list of 177 items (version 1.0) was generated by treated CD patients (n = 9), caregivers (n = 2), healthcare providers (n = 7), and results of a MEDLINE search. Item reduction was performed through content analysis and dual scaling. Patients' rating of importance was incorporated to reduce to a final version of 56 items (version 3.0). Evidence for test-retest reliability was sought through administering the QOL-CD 1 week apart and Cronbach's α of each subscale. Construct validity was assessed through extreme group analysis and comparison with the normal Canadian population. Concurrent validity was sought through comparison with the SF-36, Functional Assessment of Cancer Therapy-Brain (FACT-Br), and Karnofsky Performance Status (KPS). Perioperative testing was conducted on CD patients (n = 25) against nonfunctioning pituitary adenoma controls (n = 25) through pre- and postoperative testing. RESULTS: A total of 96 CD patients (86 females and 10 males; mean age 45.23 ± 14.16 years) participated. The QOL-CD was feasible (mean completion time 15 minutes, with 70% believing accurate capture of QOL), reliable (CD 1 week apart: r = 0.86; control 1 week apart: r = 0.83; Cronbach's α: general health = 0.73, emotional health = 0.85, physical health = 0.78, mental status = 0.82, social well-being = 0.63, medical treatment = 0.54), and valid (extreme group testing p < 0.001; SF-36 and QOL-CD general health: r = 0.56, social well-being: r = 0.21, emotional health: r = 0.61, total score: r = 0.58; FACT-Br and QOL-CD physical health: r = 0.47, social well-being: r = 0.21, emotional health: r = 0.34, total score: r = 0.68; KPS and QOL-CD general health: r = 0.32, total score: r = 0.14). Perioperative testing of CD patients (n = 25) demonstrated improvement in all subscales postoperatively, with a significant difference in emotional health (p < 0.001) and physical health (p < 0.001). CONCLUSIONS: The QOL-CD questionnaire has been developed for patients with CD and has demonstrated evidence for validity and reliability.

A prospective study of the cognitive and psychiatric effects of pituitary tumours and their treatments.

Neurocognitive complaints are common in patients with pituitary tumours, particularly in memory and concentration. Past studies have shown impairments in executive function and memory, but it is not clear whether these result from direct effects of the tumour (pressure or hormonal secretion), incidental damage from radiotherapy or surgical treatments, and/or mediating psychiatric factors. This study assessed cognitive function and psychiatric state of 86 pituitary tumour patients and 18 healthy controls, pre and post-treatment, to examine the effects of tumour aetiology and treatment type. No significant cognitive impairments were found, except on verbal recognition memory. Patients with Cushing's disease showed lower verbal recognition memory than the other groups pre-treatment, but improved at follow-up. This was (at least partially) accounted for by an improvement in depression scores. Patients who were treated with surgery showed poorer verbal recognition memory than controls across all (pre- and post-treatment) time-points. Overall findings of minimal cognitive impairment in patients with pituitary tumours may reflect improved diagnostic and treatment techniques in recent years. We suggest that the verbal memory impairments identified in the Cushing's group may result from increased cortisol (directly, or mediated by depression). In the surgical groups, verbal memory impairments appeared to pre-date treatment. This may relate to treatment selection factors, rather than harmful effects of surgery itself.

Patient-Centered Outcomes with Pituitary and Parasellar Disease.

Over the last 2 decades, advances in the diagnosis and management of pituitary diseases have made it possible to attain an endocrine "cure" in a large proportion of patients. In other words, tumors can be excised or controlled with drugs, mass effects of the lesion on surrounding structures can be solved, and pituitary deficiencies can be substituted with all relevant hormones. While this is considered a satisfactory outcome for health care providers, patients often suffer from an aftermath of prior endocrine dysfunction exposure, with irreversible effects, both physically and psychologically, which have a great impact on their everyday life. Diagnostic delay, often of several years, adds a negative impact on health perception. This affects their social, professional, and family domains and determines their future life. Understanding that this may occur is important, and health care providers should offer information to prepare the patient for this difficult journey, especially in the case of acromegaly, Cushing disease, or hypopituitarism. In order to maintain a good quality of life (QoL) in the long-term, patients need to adapt to this new situation, something that may be difficult, since they often cannot continue with all the activities and rhythm they used to do. Depression is often the consequence of maladaptation to the new situation, leading to impaired QoL.

Posttraumatic stress symptoms (PTSS) in patients with Cushing's disease before and after surgery: A prospective study.

The aim of this study was to investigate the occurrence, correlated factors and prognosis of posttraumatic stress symptoms (PTSS) in patients with Cushing's disease (CD). A total of 49 patients who were newly diagnosed with CD and underwent transsphenoidal surgery in our hospital from April 2015 to August 2017 were asked to participate in this study. Another group of 49 age and sex matched healthy control participants were also included for comparison. PTSS (measured with Impact of Event Scale-Revised, IES-R), depression/anxiety (measured with Hospital Anxiety and Depression scale, HADS) and quality of life (QoL; measured with 36-item short-form, SF-36) were evaluated at pre-surgery, 6 months post-surgery and 12 months post-surgery. The results showed that at preoperative stage, 15 (30.6%) CD patients developed PTSS, and they had higher 24 h UFC, and presented worse levels of depression, anxiety and QoL compared with patients without PTSS. Although most of them recovered postoperatively, there were still 5/15 (33.3%) patients persisted with PTSS for over a year. Additionally, one patient with recurred CD developed PTSS between 6 and 12 months postoperatively. Among the whole group of CD patients, the PTSS severity showed consistent improvement after surgery, which was in accordance with the progressing trends of depression, anxiety and psychological aspects of SF-36. However, compared with healthy individuals, CD patients in remission still performed worse in physical/mental health. In conclusion, patients with CD can develop PTSS, and they may persist for over a year even after successful surgery. Combined psychological intervention is advised for these patients.

Bilateral adrenalectomy in Cushing's disease: Altered long-term quality of life compared to other treatment options.

OBJECTIVE: Bilateral adrenalectomy (BADX) has become an important treatment of Cushing's disease (CD), especially when other treatment options have failed. The aim of this study was to evaluate the long-term quality of life (QoL) of patients having undergone BADX for CD, in comparison to other therapeutic options. METHODS: Thirty-four patients with CD were identified in two French centers: 17 underwent BADX and the remaining 17 one or more of the following treatments: surgery, medical therapy or radiotherapy. Three questionnaires were filled in by each patient in order to evaluate their QoL: Short Form-36 Health Survey (SF-36), Cushing QoL questionnaire and Beck depression inventory (BDI). RESULTS: The mean age of patients was 49.3±15.2 years. Average time lapse between diagnosis and BADX was 6.1 years. Results from each questionnaire adjusted to age showed a lower QoL among patients who underwent BADX. These were significant in most aspects of the SF-36 questionnaire (bodily pain P<0.01, general health P<0.01, vitality P≤0.05, social functioning P≤0.05), as well as in the Cushing QoL questionnaire (P<0.05) and BDI (P≤0.05). Adrenal insufficiency appeared to be the major predictor of poor QoL whatever their initial treatment. CONCLUSIONS: Despite their clinical remission, patients who undergo BADX appear to be at a greater risk of suffering an impaired QoL due to more prolonged period of time with imperfectly controlled hypercortisolism combined with definitive adrenal insufficiency.

Quality of Life in Cushing's disease: A long term issue?

The purpose of this review is to describe how quality of life (QoL) is impaired in patients with hypercortisolism due to Cushing's syndrome of any aetiology, including pituitary-dependent Cushing's disease. It is worse in active disease, but improvement after successful therapy is often incomplete, due to persistent physical and psychological co-morbidities, even years after endocrine "cure". Physical symptoms like extreme fatigability, central obesity with limb atrophy, hypertension, fractures, and different skin abnormalities severely impair the affected patients' everyday life. Psychological and cognitive problems like bad memory, difficulties to concentrate and emotional distress, often associated with anxiety and depression, make it difficult for many patients to overcome the aftermath of treated Cushing's syndrome. Recent studies have shown diffuse structural abnormalities in the central nervous system during active hypercortisolism, thought to be related to the wide distribution of glucocorticoid receptors throughout the brain. Even though they improve after treatment, normalization is often not complete. Shortening the exposure to active Cushing's syndrome by reducing the often long delay to diagnosis and promptly receiving effective treatment is highly desirable, together with preparing the patient for the difficult periods, especially after surgery. In this way they are prepared for the impairments they perceive in every day life, and live with the hope of later improvement, which can be therapeutic in many instances.

Cushing's disease: the burden of illness.

Cushing's syndrome is caused by prolonged exposure to elevated cortisol levels. The most common form of endogenous Cushing's syndrome is Cushing's disease, which results from an adrenocorticotropic hormone-secreting pituitary tumour. Cushing's disease is associated with increased mortality, mostly attributable to cardiovascular complications, and a host of comorbidities such as metabolic and skeletal disorders, infections and neuropsychiatric disturbances. As a consequence, Cushing's disease substantially impairs health-related quality of life. It is crucial that the condition is diagnosed as early as possible, and that rapid and effective treatment is initiated in order to limit long-term morbidity and mortality. The initial treatment of choice for Cushing's disease is selective transsphenoidal pituitary surgery; however, the risk of recurrence after initial surgery is high and remains so for many decades after surgery. A particular concern is the growing body of evidence indicating that the negative physical and psychosocial sequelae of chronic hypercortisolism may persist in patients with Cushing's disease even after long-term surgical 'cure'. Current treatment options for post-surgical patients with persistent or recurrent Cushing's disease include second surgery, radiotherapy, bilateral adrenalectomy and medical therapy; however, each approach has its limitations and there is an unmet need for more efficacious treatments. The current review provides an overview of the burden of illness of Cushing's disease, underscoring the need for prompt diagnosis and effective treatment, as well as highlighting the need for better therapies.

Perioperative Quality of Life in Cushing's Disease.

BACKGROUND: Our study evaluated the perioperative quality of life (QoL) in Cushing's disease (CD) patients, along with correlations between patient variables and cure rate. METHODS: The 36-item Short-Form Health Survey (SF)-36 questionnaire was used to assess perioperative QoL. Patients completed one survey preoperatively and two surveys postoperatively. Retrospective chart review was conducted to collect SF-36 data as well as examine variables including: age, hospital stay, size of tumour, pathological diagnosis, timing of cure, and complication rates. Statistical analysis was conducted on the scores reported by the SF-36, and were compared with the normal Canadian population values, and to a sample of QoL from nonfunctioning pituitary tumour patients. This project was approved by University of British Columbia Research Ethics Board #H15-01572. RESULTS: In general, CD patients have relatively poor QoL that does improve as expected when cured, but not quite to normal levels. Factors associated with cure included presence of macroadenoma, confirmatory pathology, and patient age. Postoperative timing of cure appears to affect the durability of cure, with an immediate cure having a higher durability rate than delayed cure. Most recurrences occurred within 10 months postoperatively. CONCLUSIONS: This review of the perioperative QoL in CD helps to illustrate how QoL changes throughout the treatment process, how QoL compares to normal Canadian population levels, and how QoL compares to patients with nonfunctioning pituitary adenomas. As treatment outcome has such a high impact on QoL, the variables identified in this study will help to better inform patients about the treatment course.

Coping strategies have a strong impact on quality of life, depression, and embitterment in patients with Cushing's disease.

PURPOSE: Quality of life (QoL) and psychosocial well-being are substantially impaired in patients with Cushing's disease (CD), not only at the acute illness stage but also after therapy; however, the reason for these impairments remains unclear. METHODS: In this cross-sectional, patient-reported outcome study, we conducted a postal survey on psychosocial impairment and coping strategies in patients after surgical treatment of CD in three large tertiary referral centers. In total, 176 patients with CD completed a compilation of self-assessment inventories pertaining to depression (Hospital Anxiety and Depression Scale, HADS), QoL (Short Form SF-36, Tuebingen CD; Tuebingen CD-25), coping style (Freiburg questionnaire on coping with illness, FKV-LIS), and embitterment (Bern Embitterment Inventory), on average 6.8 ± 6.66 years after surgery. Regression analyses were performed to identify predictors of psychosocial impairment. RESULTS: At the time of the study, 21.8 % of patients suffered from anxiety, 18.7 % experienced an above-average feeling of embitterment, and 13.1 % suffered from depression. Maladaptive coping styles (FKV-LIS subscales depressive coping and minimizing importance) emerged as robust and strong predictors of psychosocial impairment in all inventories; while age, sex, and hydrocortisone intake failed to explain the variance in these measures. CONCLUSION: Similar to several studies in non-pituitary patient cohorts (e.g., patients with multiple sclerosis or lower back pain), our results indicate that psychosocial impairment in CD is significantly influenced by how the patient deals with the illness. Therefore, psychological training of positive coping styles could be a helpful complementary therapy in the overall treatment strategy of CD.

The development and validation of the Leiden Bother and Needs Questionnaire for patients with pituitary disease: the LBNQ-Pituitary.

BACKGROUND: Patients report persisting impairment in quality of life (QoL) after treatment for pituitary disease. At present, there is no questionnaire to assess (a) whether patients with pituitary disease are bothered by these consequences, and (b) their needs for support. OBJECTIVE: To develop and validate a disease-specific questionnaire for patients with pituitary disease which incorporates patient perceived bother related to the consequences of the disease, and their needs for support. METHODS: Items for the Leiden Bother and Needs Questionnaire for patients with pituitary disease (LBNQ-Pituitary) were formulated based on results of a recent focus group study (n = 49 items). 337 patients completed the LBNQ-Pituitary and six validated QoL questionnaires (EuroQoL-5D, SF-36, MFI-20, HADS, AcroQol, CushingQoL). Construct validity was examined by exploratory factor analysis. Reliabilities of the subscales were calculated with Cronbach's alphas, and concurrent validity was assessed by calculating Spearman's correlations between the LBNQ-Pituitary and the other measures. RESULTS: Factor analyses produced five subscales (i.e., mood problems, negative illness perceptions, issues in sexual functioning, physical and cognitive complaints, issues in social functioning) containing a total of 26 items. All factors were found to be reliable (Cronbach's alphas all ≥.765), and the correlations between the dimensions of the LBNQ-Pituitary and other questionnaires (all P ≤ .0001) demonstrated convergent validity. 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 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.

Cushing Disease Presenting as Primary Psychiatric Illness: A Case Report and Literature Review.

We report the case of a woman with long-standing refractory depression and psychotic features who was eventually diagnosed with Cushing disease. After surgical treatment of a pituitary adenoma, she experienced gradual psychiatric recovery and was eventually able to discontinue all psychotropic medication. We review the psychiatric components of Cushing disease, implications of psychiatric illnesses for the treatment and prognosis of Cushing disease, and potential pathophysiological mechanisms linking glucocorticoid excess to psychiatric illness.

Comorbidities in Cushing's disease.

INTRODUCTION: Cushing's disease is a rare disorder characterized by overproduction of ACTH from a pituitary adenoma leading to hypercortisolemia that in turn leads to increased morbidity and mortality. METHODS: Here we review the comorbidities associated with Cushing's disease and their impact on quality of life and mortality. RESULTS: Recent evidence suggests that correction of hypercortisolemia may not lead to complete resolution of comorbidities associated with this condition. In particular, increased cardiovascular risk may persist despite long-term remission of hypercortisolemia. This may be related to persistence of visceral adiposity, adverse adipokine profile, glucose intolerance, hypertension, dyslipidemia, atherosclerosis and a procoagulant phenotype. Prior prolonged exposure to glucocorticoids also may have irreversible effects on the central nervous system, leading to persistent cognitive and mood alterations. Osteoporosis and fractures, especially vertebral fractures, can further add to morbidity and a poor quality of life. Normalization of cortisol levels leads to significant improvement in comorbidities but long-term data regarding complete resolution are lacking and need further study. CONCLUSION: Early diagnosis and treatment of hypercortisolemia, aggressive management of comorbidities along with long-term follow-up is crucial for the optimal recovery of these patients.

Reduced sleep quality and depression associate with decreased quality of life in patients with pituitary adenomas.

OBJECTIVES: Several studies reported decreased quality of life (QoL) and sleep as well as increased rates of depression for patients with pituitary adenomas. Our aim was to explore to what extent differences in depression and sleep quality contribute to differences in QoL between patients with pituitary adenomas and controls. DESIGN: A cross-sectional case-control study. SETTING: Endocrine Outpatient Unit of the Max Planck Institute of Psychiatry, Munich, Department of Internal Medicine, Ludwig-Maximilians-University, Munich, and the Institute of Clinical Psychology and Psychotherapy, Technical University, Dresden. PARTICIPANTS: Patients with pituitary adenomas (n=247) and controls (from the DETECT cohort, a large epidemiological study in primary care patients) matched individually by age and gender (n=757). MEASUREMENTS: Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and QoL was measured by the generic EQ-5D and calculated by the time trade-off- and VAS-method. Depression was categorized as 'no depression', 'subclinical depression', and 'clinical depression' according to the Beck Depressions Inventory for patients and the Depression Screening Questionnaire for control subjects. STATISTICAL ANALYSES: General linear and generalized, logistic mixed models as well as proportional odds mixed models were calculated for analyzing differences in baseline characteristics and in different subgroups. RESULTS: Patients with pituitary adenomas showed decreased QoL (VAS index: 0.73±0.19) and sleep (PSQI score: 6.75±4.17) as well as increased rates of depression (subclinical or clinical depression: 41.4%) compared with their matched control subjects (VAS index: 0.79±0.18, PSQI score: 5.66±4.31, subclinical or clinical depression: 25.9%). We have shown that a substantial proportion of the reduced QoL (48% respectively 65%) was due to the incidence of depression and reduced sleep quality. CONCLUSIONS: These findings emphasize the importance of diagnosing depressive symptoms and sleep disturbances in patients with pituitary disease, with the ultimate goal to improve QoL in patients with pituitary adenomas.

Neuropsychiatric and cardiometabolic comorbidities in patients with previously diagnosed Cushing's disease: a longitudinal observational study.

INTRODUCTION: Only few studies have systematically investigated neuropsychiatric aspects in patients with Cushing's disease (CD). Pain syndromes have been described in patients with pituitary adenomas, but so far no systematical investigation has been conducted in patients with CD. Additionally, CD has an association with cardiometabolic comorbidities which ultimately leads to increased morbidity and mortality. Long-term treatment of the hypercortisolic state cannot prevent the persistence of an unfavourable cardiometabolic risk profile. Finally, chronic hypercortisolism is known to impact the health-related quality of life (HRQoL). We aim to systematically investigate the neuropsychiatric and cardiometabolic comorbidities, as well as assess the HRQoL, in patients with previously diagnosed CD in a longitudinal fashion. METHODS AND ANALYSIS: In this longitudinal study, we will assess 20 patients with CD displaying biochemical control 24 months after recruitment in the initial cross-sectional study (n=80). This will be a mixed cohort including patients after surgical, after radiation therapy and/or under current medical treatment for CD. Primary outcomes include changes in mean urinary free cortisol and changes in specific pain patterns. Secondary/exploratory neuropsychiatric domains include depression, anxiety, personality, sleep, body image and quality of life. Secondary/exploratory cardiometabolic domains include anthropometric parameters, cardiometabolic risk biomarkers and insulin resistance. Additional domains will be investigated if warranted by clinical indication. Safety assessment under medical therapy will include liver enzymes, ECG abnormalities and hyperglycaemia. ETHICS AND DISSEMINATION: Risk of damage from study-conditioned measures is very small and considered ethically justified. Dual-energy X-ray absorptiometry may call for detailed fracture risk assessment. However, the radiation dose is very small and only administered on clinical indication; therefore, it is considered ethically justified. This protocol has been approved by the local medical ethics committee.

Quality of life in Cushing's syndrome.

INTRODUCTION: Cushing syndrome (CS) of any etiology (adrenal, pituitary or ectopic) impacts negatively on health-related quality of life (QoL), especially in active hypercortisolism but also after endocrine cure. Both generic questionnaires like the short-form 36 health survey -SF-36- and the derived SF-12, or the Hospital Anxiety and Depression Scale (HADS), and disease-specific measures like the CushingQoL and the Tuebingen CD-25 questionnaires have provided information on the impact of CS on patients perceived health. MATERIALS AND METHODS: Studies published since January 2013 until November 2014 on QoL in patients with CS were identified, reviewed and summarized. CONCLUSIONS: Treatment of CS improves patients perceived QoL, but it often takes many months and often never normalizes. In parallel to persistent QoL impairment in cured CS, brain and cerebellar volume are reduced. Depression, anxiety and cognitive dysfunction are common. Pediatric patients with CS also present worse QoL than normal children, as well as additional issues like delayed growth and pubertal development, next to abnormal body composition, psychological and cognitive maturation. Fluoxetine has been suggested as a neuroprotectant and antidepressant for patients with CS, although no prospective studies are yet available. The CushingQoL questionnaire has been mapped to well-validated instruments like SF-36 or EQ-5D, and therefore may be used in cost-utility and other health economy studies.

Gender differences in presentation and outcome of patients with Cushing's disease in Han Chinese.

The purpose of this study was to assess gender-related distinction in the performance of Cushing's disease (CD) regarding clinical features, radiological findings, neurological and endocrine status, surgical outcome, and quality of life in Han Chinese. A retrospective study was conducted on 87 patients treated by trans-sphenoidal surgery, between 2006 and 2011, at a single treatment center in Shandong Provincial Hospital, China. Features of CD were compared and quality of life was analyzed between genders. The female-to-male ratio was 2.78: 1. Results showed that men have a younger age of diagnosis (P<0.001), a larger adenoma diameter (P<0.001), and a higher invasion rate (P=0.032) and apoplexy rate (P=0.04) than women. To be specific, compared with women, men are more prone to suffering from osteoporosis, hypokalemia, sexual dysfunction, and hypertension (P<0.05), have significantly higher preoperative and postoperative (six months after surgery) cortisol levels (P<0.001, P=0.003) and a higher recurrence rate (30.43% vs. 7.81%; P=0.028). No significant differences were seen in the CushingQoL scores between genders. Therefore, male patients with CD need more careful and long-term follow-up than female patients.

Similar psychopathological profiles in female and male Cushing's disease patients after treatment but differences in the pathogenesis of symptoms.

BACKGROUND: Female Cushing's disease (CD) patients with active disease present more frequently with depression compared to their male co-sufferers. This study investigated whether the gender difference prevails after remission and whether gender-specific factors contributing to mental health exist. METHODS: 72 biochemically cured CD patients (11 male, mean age 45.9 ± 13.7 years) who underwent transsphenoidal tumour removal filled out the Symptom Checklist-90-Revised inventory on average 42.1 ± 32.9 months after surgery. Multiple regression analyses included the following independent factors: (i) age, (ii) presence of comorbidities, (iii) presence of hypocortisolism, (iv) presence of hypopituitarism, (v) disease duration until diagnosis, (vi) time elapsed since surgery, and (vii) postoperative radiotherapy to predict postoperative psychopathology. RESULTS: Regarding the Global Severity Index, 23.0% of the female and 27.3% of the male CD patients presented with abnormal scores. In all nine dimensions, psychopathological abnormalities were present in both female and male patients with the same frequency and intensity (each p > 0.05). Prolonged time to diagnosis was a strong predictive factor for worse psychopathological status only in male patients. Among female patients, only the presence of comorbidities and to some extent pituitary deficiencies were related to psychopathological status. CONCLUSIONS: During the remission phase of CD, female and male patients present with similar psychopathological profiles. In males, long-term biochemical effects of previous hypercortisolism seem to be salient for psychopathology. In contrast, in females, the presence of comorbidities/stressors they have to cope with is the predictive factor for psychopathology. The results underline gender differences in CD and the need to separate them on various issues.

Tuebingen CD-25 is a sensitive tool to investigate health-related quality of life in Cushing's disease patients in the course of the disease.

BACKGROUND: The primary object was to investigate whether the Tuebingen CD-25 captures changes in health-related quality of life (HRQoL) sensitively in Cushing's disease (CD) and to identify factors that favour postoperative HRQoL. METHODS: 17 CD patients were scheduled for transsphenoidal tumour removal and filled out the inventory before and after surgery. The mean time elapsed after surgery was 14.4 ± 11.3 months. All patients were in remission at the second timepoint of investigation. RESULTS: HRQoL as assessed with the Tuebingen CD-25 improved significantly after successful surgical tumour removal. A large effect size (Cohen's d = 0.84) in the total score indicates good sensitivity to change. 13 patients (76.5%) showed impaired HRQoL preoperatively compared with a general population sample. Postoperatively, 35.3% of the patients still suffered from an impaired HRQoL. Stepwise linear regression analysis revealed that less comorbidities (≤2) and greater morning cortisol decrease were promotive factors for better postoperative HRQoL (p < 0.05). The postoperative improvement in HRQoL could be best predicted by the presence of preoperative HRQoL impairment and age of the patients, i.e. patients who were younger were more likely to improve. Moreover, patients without postoperative pituitary deficiencies improved significantly more in the cognition scale. A tendency towards more improvement in overall HRQoL was observed in non-hypocortisolaemic patients. CONCLUSIONS: The Tuebingen CD-25 has proved to be a capable and sensitive instrument to investigate HRQoL in the course of disease. The number of postoperative comorbidities had the greatest impact on postoperative well-being.

Increased prevalence of anxiety-associated personality traits in patients with Cushing's disease: a cross-sectional study.

BACKGROUND/AIMS: Chronic hypercortisolism in Cushing's disease (CD) has been suggested to contribute to an altered personality profile in these patients. We aimed to test this hypothesis and attempted to determine the effects of disease- and treatment-related factors that might moderate an altered personality in CD. METHODS: We assessed 50 patients with CD (74% biochemically controlled) and compared them to 60 patients with non-functioning pituitary adenomas (NFPA) and 100 age- and gender-matched mentally healthy controls. Personality was measured by two standardized personality questionnaires, TPQ (Cloninger personality questionnaire) and EPQ-RK (Eysenck personality questionnaire-RK). RESULTS: Compared to mentally healthy controls, CD patients reported significantly less novelty-seeking behaviour, including less exploratory excitability and less extravagance. On harm avoidant subscales, they presented with more anticipatory worries and pessimism, higher fear of uncertainty, shyness with strangers, fatigability and asthenia. Moreover, CD patients appeared to be less extraverted, more neurotic and socially desirable. CD patients differed from NFPA patients in terms of higher neuroticism scores, and NFPA patients did not show altered novelty-seeking behaviour or extraversion. In the subgroup analysis, CD patients with persistent hypercortisolism displayed significantly higher fear of uncertainty, fatigability and asthenia, indicating high harm avoidance in total, than those in biochemical remission. CONCLUSION: Patients with CD showed a distinct pattern of personality traits associated with high anxiety in combination with traits of low externalizing behaviour. Such personality changes should be taken into account in the diagnosis and treatment of CD patients, as they might interfere with the patient-physician communication and/or challenge the patients' social and psychological functioning.

Evaluation of depression, quality of life and body image in patients with Cushing's disease.

The aim of this study was to evaluate patients with Cushing's disease (CD) who had undergone transsphenoidal surgery in terms of depression, quality of life (QoL), and perception of body image in comparison to healthy controls. Forty patients with CD and 40 healthy controls matched for demographic characteristics were included in the study. The subjects were evaluated with the Beck depression inventory (BDI), the health survey-short form (SF-36) and the multidimensional body-self relations questionnaire (MBSRQ). Subgroups of the patients with CD were formed on the basis of remission status and BDI scores. In this study, QoL in the general health category and body image were lower in the patients with CD than in the healthy subjects. However, no differences in depression scores were found between the two groups. When the CD group was evaluated according to remission rate, the mean BDI score was significantly higher in the CD patients without remission than in both the CD patients with remission and the healthy subjects (p = 0.04). However, the physical functioning, bodily pain and general health scores of the CD patients without remission on the SF-36 questionnaire were lower than in the CD patients in remission and the healthy subjects (p = 0.002, p = 0.04, p = 0.002, respectively). Fitness evaluation, health evaluation and body areas satisfaction scores of the MBSRQ were significantly different in the three groups (p = 0.003, p = 0.009 and p = 0.001, respectively). In this study, patients with CD were found to have lower QoL, lower body image perception and higher levels of depression compared to healthy controls, particularly if the disease is persistant despite surgery.