Shared decision-making and detection of comorbidities in an online acromegaly consultation with and without the Acromegaly Disease Activity Tool ACRODAT® using the simulated person approach.

OBJECTIVE: A patient-centered approach to the management of acromegaly includes disease activity control, shared decision-making and identification of comorbidities. The Acromegaly Disease Activity Tool (ACRODAT®) is intended to assist physicians in providing such holistic management. The present study investigated this claim using the simulated person (SP) approach. METHODS: We studied patient-doctor interaction via online video consultation in a randomized prospective study design with SPs trained to simulate a specific acromegaly profile. We analyzed the proportion of conversation time devoted to health content and the specific acromegaly and comorbidity relevant categories mentioned in the conversation. We collected physicians' feedback on the usefulness of ACRODAT®, SPs subjective perception of the quality of the conversation and compared consultations with and without ACRODAT® using a qualitative approach. RESULTS: The sample (N = 30) consisted of endocrinologists treating patients with acromegaly in Germany. For SP-physician interactions (N = 60), the proportion of time spent on conversation content (e.g. IGF-I, quality of life) was distributed according to the focus of the patient profile. Comorbidities were less well identified than the need for a change in therapy. Only 18.3% of the SPs were actively asked to participate in the decision-making process. ACRODAT® did not lead to any significant differences in the course of the discussion. CONCLUSIONS: Shared decision-making was underrepresented in this SP-physician interaction in acromegaly management. Physicians adapted the content of the discussion to the SP's needs, but did not adequately address comorbidities. According to the analysis criteria used, ACRODAT® did not contribute to a more holistic patient management in the present study.

Exploring potential influencing factors of inadherence to specialist aftercare and long-term medication in patients with acromegaly.

PURPOSE: To improve the understanding of adherence as one major factor of disease control in acromegaly patients, we systematically assessed patients' motivations to adhere to advised follow-up schedules and recommended medication for acromegaly. METHODS: Cross-sectional, postal questionnaire study on adult patients with acromegaly, operated upon a growth hormone producing pituitary adenoma more than 1 year ago in two tertiary treatment centers. We assessed demographic and clinical characteristics, disease status, adherence to acromegaly medication and/or aftercare, and the five dimensions defined by the World Health Organization influencing adherence. Wherever applicable, we included validated short scales. The answers of 63 patients (33 f, 30 m; mean age 56.1 y) were analyzed. RESULTS: Patients with problems in adherence to aftercare had a significantly lower subjective symptomload than those adherent to aftercare (p = 0.026) and a lower perceived need for treatment (p = 0.045). Patients with adherence problems to medication had a higher subjective symptomload than those without (p = 0.056). They also tended to have shorter consultations, were significantly more often dissatisfied with the duration of their medical consultations (42% vs 4.8%, p = 0.019) and tended to find that their physician explained potential difficulties with adherence less well than patients without adherence problems (p = 0.089). CONCLUSIONS: To our knowledge, this is the first study which explored adherence to medication and aftercare in patients with acromegaly, taking into account potential influencing factors from all areas defined by the WHO model of adherence. Of the modifiable factors of adherence, patient-doctor relationship seemed to play a crucial role and could be one leverage point to improve adherence.

The effect of coping strategies on health-related quality of life in acromegaly patients.

PURPOSE: Patients with acromegaly oftentimes exhibit a reduced physical and psychological health-related quality of life (HRQoL). Maladaptive coping styles are associated with poor HRQoL in a number of diseases and patients with pituitary adenomas in general exhibit less effective coping styles than healthy controls. This study aimed to assess coping strategies in acromegaly patients in order to explore leverage points for the improvement of HRQoL. METHODS: In this cross-sectional study, we administered self-report surveys for coping strategies and HRQoL (Short Form SF-36, Freiburg questionnaire on coping with illness, FKV-LIS) in patients with acromegaly. These were set into relation with a variety of health variables. RESULTS: About half of the 106 patients (44.3% female) with a mean age of 56.4 ± 1.3 years showed impaired physical and psychological HRQoL on average 11.2 years after the initial diagnosis. Body mass index, age at survey date and concomitant radiotherapy explained 27.8% of the variance of physical HRQoL, while depressive coping added an additional 9.2%. Depressive coping style and trivialization and wishful thinking were pivotal predictors of an impaired psychological HRQoL with a total explained variance of 51.6%, whereas patient health variables did not affect psychological HRQoL. CONCLUSION: Our results show that maladaptive coping styles have a substantial negative impact on psychological HRQoL in patients with acromegaly, whereas physical HRQoL is influenced to a lesser extent. Specialized training programs aimed at improving coping strategies could reduce long-term disease burden and increase HRQoL in the affected patients.

Measuring Patient Experience and Patient Satisfaction-How Are We Doing It and Why Does It Matter? A Comparison of European and U.S. American Approaches.

(1) Background: Patients' experiences and satisfaction with their treatment are becoming increasingly important in the context of quality assurance, but the measurement of these parameters is accompanied by several disadvantages such as poor cross-country comparability and methodological problems. The aim of this review is to describe and summarize the process of measuring, publishing, and utilizing patient experience and satisfaction data in countries with highly developed healthcare systems in Europe (Germany, Sweden, Finland, Norway, the United Kingdom) and the USA to identify possible approaches for improvement. (2) Methods: Articles published between 2000 and 2021 that address the topics described were identified. Furthermore, patient feedback in social media and the influence of sociodemographic and hospital characteristics on patient satisfaction and experience were evaluated. (3) Results: The literature reveals that all countries perform well in collecting patient satisfaction and experience data and making them publicly available. However, due to the use of various different questionnaires, comparability of the results is difficult, and consequences drawn from these data remain largely unclear. (4) Conclusions: Surveying patient experience and satisfaction with more unified as well as regularly updated questionnaires would be helpful to eliminate some of the described problems. Additionally, social media platforms must be considered as an increasingly important source to expand the range of patient feedback.

Not Simply a Structural Problem: Psychological Determinants of Headache in Patients with Tumors of the Sellar Region.

OBJECTIVE: Headache in patients with tumors of the sellar region (TSR) has previously been attributed entirely to biomechanical causes. This study aimed to investigate the influence of psychological determinants for the occurrence of and disability due to headaches in patients with TSR. METHODS: This was a cross-sectional single-center study with a logistic regression approach. Eighty-four patients (75%) with pituitary adenomas and 28 with other TSR prior to first-time neurosurgery were investigated. One-hundred and twelve patients received standardized questionnaires on personality, headache characteristics, and disability due to headache. Fifty-nine patients additionally filled in questionnaires about coping with stress and pain catastrophizing. Separate logistic regression models were used to predict the risk of headache occurrence and disability due to headache by personality, stress coping, and pain catastrophizing. RESULTS: Conscientiousness, neuroticism, and pain catastrophizing were significant predictors of headache occurrence. The amount of explained variance for both models predicting headache occurrence was comparable to that in primary headache. Neuroticism, pain catastrophizing, and humor as a coping strategy predicted disability due to headache with a high variance explanation of 20-40%. CONCLUSION: For the first time, we report data supporting a strong psychological influence on headache and headache-related disability in patients with TSR, which argue against purely mechanistic explanatory models. Physicians treating patients with TSR and headaches should adopt an integrative diagnostic and treatment approach, taking the biopsychosocial model of pain into account.

Illness-related burden, personal resources and need for support in patients with acromegaly: Results of a focus group analysis.

OBJECTIVE: It was the aim of this study to evaluate illness-related burdens and support needs of patients with acromegaly to identify hitherto unadressed research questions and to open up avenues for improvements in patient care. This was done by using the focus group approach as a qualitative research method. DESIGN: Seven patients with acromegaly took part in a focus group moderated by an external medical communication specialist. The discourse focused on topics such as impact of the illness on everyday life, support needs and personal resources. The discussion was recorded and transcribed and analyzed by qualitative content analysis. RESULTS: Participants reported a huge impact of acromegaly on daily life, ranging from time expenditure for managing their illness, to bodily and mental sequelae and strain caused by physical disfigurement. Patients' coping strategies included family support, physical activities and humor. The participants wished for a sound patient-doctor relationship, more interdisciplinary and holistic treatment, medical rehabilitation services with special knowledge on acromegaly-related morbidity, a stable contact person in the medical process and reliable information material for themselves and their relatives. CONCLUSIONS: The results provide multi-facetted impressions of the overwhelming impact of acromegaly and unmet support needs of the afflicted patients. Further quantitative research is necessary to examine the generalisibility of the present results in order to implement tailored support measures. We suggest to develop standardized questionnaires to explore the prevalence and severity of the addressed problems in a large patient sample and to establish screening instruments to monitor disease burden in clinical practice.

Adults' Adherence to Growth Hormone Replacement in Relation to Medication-Related Beliefs, Coping and Quality of Life - An Exploratory Analysis.

Introduction: Little is known about psychological reasons associated with adherence to growth hormone (GH) replacement therapy (GHRx) in adults. As in other chronic diseases, medication-related beliefs, coping strategies and disease impact on quality of life (QoL) might play an important role. We thus explored these psychological factors in relation to adherence in patients with GH deficiency (GHD) in order to find leverage points for the improvement of adherence. Patients and Methods: Cross-sectional analysis including 107 adult GHD patients on GHRx who completed self-assessment inventories on health-related QoL (Short-Form SF-36), coping style (Freiburg questionnaire on coping with illness, FKV-LIS) and medication beliefs (Beliefs about Medicine questionnaire, BMQ). Results were correlated to general and GH-specific adherence to medication. Results: In the BMQ, 92.5% of the patients (n=99) reported a strong belief in the need for their medication, which correlated significantly with general adherence (rs = 0.325). Active coping was significantly related to general (rs = 0.307) and GH-specific adherence (rs = 0.226). Better mental QoL (rs = 0.210) but worse physical QoL (rs = -0.198; all p < 0.05) were related to higher GH-specific adherence. Older age was associated with a higher degree of active coping, a higher belief in the necessity of medication and worse physical QoL. Conclusion: We provide preliminary data that most GHD patients on GHRx are strongly convinced of their need for medication and that adherence to GHRx is influenced by coping strategies and QoL. Patients with impaired psychological QoL are less able to translate their convictions into good adherence, a phenomenon to be addressed in future research.

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

PURPOSE: To present a systematic review of the presence and severity of neuropsychological impairment in the six main neuropsychological domains (attention, executive function, language, visuospatial processing, intelligence, and memory) in patients with Cushing's disease (CD) and/or Cushing's Syndrome (CS) at various stages of the illness. The work aims to identify neuropsychological leverage points for focused diagnosis and rehabilitation in CS/CD patients. METHODS: A pubmed literature search was performed and augmented by searching the reference lists of review articles identified by this search strategy. After excluding irrelevant hits, we systematically extracted data from 27 studies for each main neuropsychological domain, differentiating between active disease, short- and long-term remission. RESULTS: The literature gives evidence for neuropsychological impairment in all domains in Cushing patients with active disease. The most consistent impairments concerned memory and visuo-spatial processing, whereas the data are discordant for all other domains. Significant improvement of neuropsychological function - although not returning to normal in all domains - is shown in short-term and long-term remission of the disease. However, the published literature is thin, suffering from repetitive subsample analyses publishing, methodological concerns as lack of control for confounders such as depression. CONCLUSIONS: Memory is the most extensively investigated domain in CS/CD patients and impairment is most prominent in active disease. Patients should be counseled that neuropsychological function will improve with normalization of hypercortisolism and over time. More studies with more stringent methodological criteria, larger patient samples and controlling for confounders are required to enhance our understanding of neuropsychological function in patients with CS/CD.

Motivation for and adherence to growth hormone replacement therapy in adults with hypopituitarism: the patients' perspective.

INTRODUCTION: While reasons for non-adherence in children requiring growth hormone (GH) replacement (GH-Rx) are well researched, few studies have investigated adherence in adult GH deficient patients. Against the background of the adverse medical sequelae of untreated severe GH deficiency (GHD) in adults, we explored adherence to GH-Rx and associated factors in this patient group. METHOD: Cross-sectional analysis including 107 adult patients with severe GHD on GH-Rx, 15 untreated GDH patients and 19 who had discontinued therapy. Patients completed self-developed ad hoc surveys on adherence to medication and GH-Rx, specific beliefs about GH-Rx, side effects and burden of injection, reasons for never receiving or dropping out of therapy, respectively. RESULTS: Adherence to GH-Rx was high (mean 15.8/18 points on the self-developed adherence score) and significantly correlated with general medication adherence. Higher age was significantly associated with better adherence to GH-Rx, while injection side effects, duration of treatment or device used were not. The most frequent reasons for not being on GH-Rx apart from medical reasons included fear of side effects, lack of belief in treatment effects and dislike of injections. In patients not on GH-Rx, the proportion of patients in employment was significantly smaller than in the treatment group, despite similar age and comorbidities. CONCLUSIONS: Adherence to GH-Rx was high for those patients on therapy. Instead of focusing on improving adherence in those adults already on GH-Rx, efforts should be undertaken to ally fear of side effects and provide education on positive treatment effects for those eligible but not receiving therapy.

Support Needs of Patients with Cushing's Disease and Cushing's Syndrome: Results of a Survey Conducted in Germany and the USA.

BACKGROUND: Cushing's disease (CD) and Cushing's syndrome (CS) are chronic illnesses, characterized by symptoms of prolonged hypercortisolism, which often changes to hypocortisolism after successful treatment. In view of the high disease burden of CD/CS patients and long-term impaired quality of life, the present survey was conducted to gain information about subjective illness distress and patients' specific needs in terms of supportive measures beyond medical interventions. PATIENTS AND METHODS: Cross-sectional questionnaire study including patients with CD treated in 2 German neurosurgical tertiary referral centers and CD/CS patient members of a US-based patient support group completed a survey inquiring about disease burden, coping strategies, and support needs. Additionally, the degree of interest in different offers, e.g., internet-based programs and seminars, was assessed. RESULTS: 84 US and 71 German patients answered the questionnaire. Patients in both countries indicated to suffer from Cushing-related symptoms, reduced performance, and psychological problems. 48.8% US patients and 44.4% German patients stated that good medical care and competent doctors helped them the most in coping with the illness. US patients were more interested in support groups (p = 0.035) and in courses on illness coping (p = 0.008) than the German patients, who stated to prefer brochures (p = 0.001). 89.3% of US patients would attend internet-based programs compared to 75.4% of German patients (p = 0.040). There were no differences between groups for the preferred duration of and the willingness to pay for such a program, but US patients would travel longer distances to attend a support meeting (p = 0.027). CONCLUSION: Patients in both countries need skilled physicians and long-term medical care in dealing with the effects of CD/CS, whereas other support needs differ between patients of both countries. The latter implies that not only disease-specific but also culture-specific training programs would need to be considered to satisfy the needs of patients in different countries.

Melatonin secretion following brain midline irradiation is diminished, but not correlated with subjective sleep disturbances.

OBJECTIVE: Cranial irradiation for brain tumours or leukaemias has been related to cognitive, endocrine and psychosocial late effects as well as sleep disturbances and increased daytime sleepiness. Studies suggest that cranial irradiation might impact on pineal melatonin secretion. Melatonin is an important regulator in human circadian rhythms and the sleep-wake cycle. The objective of this study was to investigate melatonin secretion, subjective sleep parameters and their interplay in a cohort of cranially irradiated head and brain tumour and leukaemia survivors at least 3 years after radiotherapy. DESIGN: Cross-sectional study. PATIENTS: Thirty-eight adults. MEASUREMENTS: Melatonin secretion was evaluated by measuring its metabolite 6-sulphatoxymelatonin in collected overnight urine. Subjective sleep quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. The Beck Depression Inventory II was used to screen for depressive symptoms because of their impact on sleep. RESULTS: Patients irradiated in the brain midline had significantly lower melatonin secretion (P = 0.008). Subjects exhibited a high prevalence of sleeping difficulties, daytime sleepiness and depression, with females and overweight subjects particularly affected. Melatonin values and subjective sleep parameters did not correlate with each other or with treatment and most patient variables. CONCLUSIONS: Our data suggest that radiation exposure to the pineal gland negatively affects melatonin secretion. This lack of pineal melatonin does not influence subjective sleep quality. As melatonin has important antioxidant and cancer-protective effects, further research is necessary to elucidate whether these patients have an increased risk of developing secondary neoplasms and other radiation late effects.

Oro-dental pathologies in acromegaly.

PURPOSE: Oro-dental pathologies (ODP) such as enlargement of the tongue, mandibular prognathism, and spaced teeth are characteristic features of acromegaly. Their frequency of occurrence during the course of the disease is largely unresolved. Purpose of this study was to assess ODP and oro-dental treatments in patients with acromegaly with regard to the length of the diagnostic process, tumor histology, and quality of life (QoL). METHODS: Single-center retrospective survey study using questionnaires on dental symptoms, diagnostic process, and treatment in patients with acromegaly operated on a growth hormone-secreting pituitary adenoma. The association between ODP and QoL was assessed using the Short-Form 36 (SF-36) Health Survey. RESULTS: 145/314 patients completed the questionnaires. 80.7% were affected by any ODP, most frequently enlargement of the tongue (57.9%), spaced teeth (42.8%), mandibular growth (24.1%), and mandibular prognathism (22.1%). ODP were significantly more frequent in patients with sparsely vs. densely granulated adenomas (p = 0.045). Early diagnosis within 2 years was associated with significantly fewer ODP than later diagnosis (68.5 vs. 87.2%, p = 0.009). Treatments included dental crowns (16.6%), dental bridges (12.4%), dental implants (9.7%), dental prostheses (3.4%), orthodontal (i.e., braces, 6.9%), and surgical correction of the teeth (2.1%). Physical QoL was significantly lower in patients with ODP than in those without (p = 0.014). CONCLUSION: In our large series of patients, four of five patients were affected by ODP at any time during the course of the disease. The results highlight the importance of early identification and treatment of oro-dental problems in patients with acromegaly as hallmarks of the disease.

Presence of headache and headache types in patients with tumors of the sellar region-can surgery solve the problem? Results of a prospective single center study.

PURPOSE: Headache is a common presenting feature of patients with pituitary adenomas and other tumors of the sellar region. However, at present, it still is unclear whether the headache is actually caused by the tumor. To explore whether there is a relation, we examined in detail the headache types, their relationship to the underlying pathology, and if the headache responded to neurosurgery in a prospective study design. METHODS: One hundred twelve patients with tumors of the sellar region scheduled for neurosurgery in a single center were analyzed for presence and quality of headache before surgery and at least 3 months after surgery. Patients received headache and depression self-rating inventories, presented on a handheld computer (PainDetect®). Clinical variables thought to impact on headache were analyzed in conjunction with the inventories. RESULTS: Fifty-nine (53%) patients reported headache in the 3 months prior to neurosurgery, 49 (44%) had headache at the time of filling in the questionnaires. The four patients with pituitary apoplexy described thunderclap headache. In the other patients diverse headache types were encountered, most frequently migraine. Untreated gonadotroph deficiency was significantly associated with absence of headache, while none of the other clinical and morphological variables related to headache. Presence of headache and disability due to headache were not significantly reduced after surgery. CONCLUSION: Apart from pituitary apoplexy we detected no specific headache type in our patient group and no significant improvement of headache after neurosurgery. Headache alone constitutes neither a valid diagnostic marker for the presence of tumors of the sellar region nor a sufficient indication for tumor removal.

PREDICTORS OF QUALITY OF LIFE IN 165 PATIENTS WITH ACROMEGALY: RESULTS FROM A SINGLE-CENTER STUDY.

OBJECTIVE: Even if treated, acromegaly has a considerable impact on patient quality of life (QoL); despite this, the exact clinical determinants of QoL in acromegaly are unknown. This study retrospectively examines a cohort of treated patients with acromegaly, with the aim of identifying these determinants. METHODS: Retrospective survey analysis, with 165 patients included in the study. All patients completed a survey, which included demographic data and the clinical details of their disease, the Short Form-36 Health Survey (SF-36), the revised Beck Depression Inventory (BDI-II), and the Bern Embitterment Inventory (BEI). Stepwise regression was used to identify predictors of QoL. RESULTS: The strongest predictors of the physical component score of the SF-36 were (in order of declining strength of association): Delay between first presentation of the disease and diagnosis, body mass index (BMI), number of doctors visited before the diagnosis of acromegaly, and age at diagnosis. For the mental component score, the strongest predictors were: number of doctors visited, previous radiotherapy, and age at study entry; and, for the BDI-II score: number of doctors visited, previous radiotherapy, age at study entry, and employment status at the time of diagnosis. The following were predictors of the BEI score: number of doctors visited, and age at study entry. CONCLUSION: Diagnostic delay and lack of diagnostic acumen in medical care provision are strong predictors of poor QoL in patients with acromegaly. Other identified parameters are radiotherapy, age, BMI, and employment status. An efficient acromegaly service should address these aspects when devising disease management plans. ABBREVIATIONS: BDI-II = Beck Depression Inventory II BEI = Bern Embitterment Inventory BMI = body mass index IGF-1 = insulin-like growth factor 1 MCS = mental component summary (score) PCS = physical component summary (score) QoL = quality of life SDS = standard deviation score SF-36 = Short Form-36 Health Survey.

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.

Diagnosis and management of acromegaly: the patient's perspective.

PURPOSE: Early diagnosis is a success factor for the prevention of long-term comorbidity and premature death in patients with acromegaly, but large-scale data on the diagnostic process and disease management are scarce. Therefore, we aimed to evaluate the diagnostic process, implementation of treatment and changes in life situation in patients with acromegaly, focusing on sex-specific differences. METHODS: Non-interventional patient-reported outcome study. 165 patients with clinically and biochemically proven acromegaly were questioned about the diagnostic process and utilization of health care by means of a self-developed standardized postal survey including questions on acromegaly symptoms experienced before diagnosis, number and specialty of consulted doctors, time to diagnosis and aftercare. RESULTS: The diagnostic process took 2.9 (SD 4.53) years, during which 3.4 (SD 2.99) physicians were consulted. Women waited longer [4.1 (SD 5.53) years] than men [1.6 (SD 2.69) years; p = 0.001] for the correct diagnosis, and consulted more doctors in the process [4.0 (SD 2.99) vs. 2.7 (SD 2.84) doctors, p < 0.001, respectively]. In 48.5 % of patients, acromegaly was diagnosed by an endocrinologist (men: 45.1 %; women: 52.4 %). Overall disease duration from symptom onset until last surgery was 5.5 (SD 6.85) years, with no sex differences. A change in employment status was the most commonly reported event after diagnosis and a quarter of the patients stated that the illness had changed their lives. CONCLUSIONS: Our findings confirm the urgent need to increase awareness of the clinical manifestation of acromegaly to facilitate an earlier diagnosis of the disease and to provide diagnostic equality across the sexes.

EZH2 is highly expressed in pituitary adenomas and associated with proliferation.

Enhancer of zeste homolog 2 (EZH2) is a core epigenetic regulator, playing a crucial role in cell cycle regulation. The protein is known to be associated with proliferation and worse outcome in several tumor entities. In this study, we immunohistochemically investigated the expression pattern of EZH2 in a large cohort of pituitary tumors. These results were correlated with clinical features and double immunofluorescence stainings (DIS) were conducted to evaluate co-expression of EZH2 and proliferation marker Ki-67. Furthermore, we analyzed the effect of EZH2 inhibition on cell proliferation in vitro using the pituitary cell line AtT-20. While in the normal anterior pituitary EZH2 was almost absent, the cohort of tumors showed enhanced expression levels (p ≤ 0.0005). This was positively associated with Ki-67 indices (r = 0.834, p ≤ 0.0005) and DIF confirmed a predominant co-expression of both markers. In vitro experiments revealed a significant (p ≤ 0.05) decrease of tumor cell proliferation using the EZH2 inhibitor GSK126. Our results further support that epigenetic events are involved in the pathogenesis and biology of pituitary adenomas (PA). Therefore, EZH2 may function as a new potential target for therapeutic interventions in PA.

Validation of the Tuebingen CD-25 Inventory as a Measure of Postoperative Health-Related Quality of Life in Patients Treated for Cushing's Disease.

BACKGROUND: To evaluate the construct and criterion validity of the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25) for application in patients treated for Cushing's disease (CD). METHODS: A total of 176 patients with adrenocorticotropin hormone-dependent CD (144 of them female, overall mean age 46.1 ± 13.7 years) treated at 3 large tertiary referral centers in Germany were studied. Construct validity was assessed by hypothesis testing (self-perceived symptom reduction assessment) and contrasted groups (patients with vs. without hypercorticolism). For this purpose, already existing data from 55 CD patients was used, representing the hypercortisolemic group. Criterion validity (concurrent validity) was assessed in relation to the Cushing's quality of life questionnaire (CushingQoL), the Short Form 36 health survey (SF-36), and the body mass index (BMI). RESULTS: Patients with self-perceived remarkable symptom reduction had significant lower Tuebingen CD-25 scores (i.e. better health-related quality of life) than patients with self-perceived insufficient symptom reduction (p < 0.05). Similarly, the mean scores of the Tuebingen CD-25 scales were lower in patients without hypercortisolism (total score 27.0 ± 17.2) compared to those with hypercortisolism (total score 45.3 ± 22.1; each p < 0.05), providing evidence for construct validity. Criterion validity was confirmed by the correlations between the Tuebingen CD-25 total score and the CushingQoL (Spearman's coefficient -0.733), as well as all scales of the SF-36 (Spearman's coefficient between -0.447 and -0.700). CONCLUSION: The analyses presented in this large-sample study provide robust evidence for the construct and criterion validity of the Tuebingen CD-25.

From first symptoms to final diagnosis of Cushing's disease: experiences of 176 patients.

OBJECTIVE: To obtain structured information on the diagnostic delay in patients with Cushing's disease (CD) from the patients perspective to provide leverage points for earlier diagnosis. DESIGN: The study includes 176 patients with ACTH-dependent CD who had received pituitary surgery completed a self-developed questionnaire on their symptomatology before the illness was diagnosed, the course and length of the diagnostic process, and the role of the involved health care professionals. METHODS: Data were analyzed statistically. Answers in free text options were categorized and counted. RESULTS: The overall diagnostic process took 3.8±4.8 years (median 2 years), during which 4.6±3.8 (1-30) physicians were consulted, most frequently the family physician (FP; 83.0%). The presented symptoms were various and often vague, e.g. 'poor general condition' (at FPs), or very common in the field of the visited specialist (i.e. 'skin changes' at dermatologists). Women recognized the first CD symptoms themselves significantly more frequently than men, whereas physicians recognized CD symptoms significantly more frequently in males. CONCLUSION: A clear difficulty of diagnosing CD seems that patients describe isolated symptoms to the FP or the respective specialists according to their fields of specialization. As FPs are contacted most frequently, they should be trained to recognize the broad spectrum of CD symptoms, especially in female patients with weight gain, and initiate endocrinological referral.