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Contains fulltext : 172679.pdf (publisher's version ) (Open Access), OBJECTIVE: To evaluate the detection of pituitary lesions at 7.0 T compared to 1.5 T MRI in 16 patients with clinically and biochemically proven Cushing's disease. METHODS: In seven patients, no lesion was detected on the initial 1.5 T MRI, and in nine patients it was uncertain whether there was a lesion. Firstly, two readers assessed both 1.5 T and 7.0 T MRI examinations unpaired in a random order for the presence of lesions. Consensus reading with a third neuroradiologist was used to define final lesions in all MRIs. Secondly, surgical outcome was evaluated. A comparison was made between the lesions visualized with MRI and the lesions found during surgery in 9/16 patients. RESULTS: The interobserver agreement for lesion detection was good at 1.5 T MRI (kappa = 0.69) and 7.0 T MRI (kappa = 0.62). In five patients, both the 1.5 T and 7.0 T MRI enabled visualization of a lesion on the correct side of the pituitary gland. In three patients, 7.0 T MRI detected a lesion on the correct side of the pituitary gland, while no lesion was visible at 1.5 T MRI. CONCLUSION: The interobserver agreement of image assessment for 7.0 T MRI in patients with Cushing's disease was good, and lesions were detected more accurately with 7.0 T MRI. KEY POINTS: Interobserver agreement for lesion detection on 1.5 T MRI was good; Interobserver agreement for lesion detection on 7.0 T MRI was good; 7.0 T enabled confirmation of unclear lesions at 1.5 T; 7.0 T enabled visualization of lesions not visible at 1.5 T. more...

Item does not contain fulltext, Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it is appropriately recognized and early treatment is rendered. Despite it being a treatable condition for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis. Although most patients are educated about "sick day rules," patients, and physicians too, are often reluctant to increase their glucocorticoid doses or switch to parenteral injections, and thereby fail to avert the rapid deterioration of the patients' condition. Therefore, more can be done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis. Hence, we will review the current literature, while also focusing on the incidence, presentation, treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress situations. more...

Contains fulltext : 172265.pdf (publisher's version ) (Closed access), BACKGROUND: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. OBJECTIVE: The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active. METHODS: In this cross-sectional study, a postal survey was performed among Dutch patients with Addison's disease on stable glucocorticoid replacement therapy with hydrocortisone or cortisone acetate. For quality of life and physical activity assessment, patients completed general and health-related quality of life and physical activity questionnaires, and scores were compared to Dutch controls. Results : A total of 328 patients with Addison's disease were studied. In patients with Addison's disease, only 45.7% met the standard of physical activity (Combinorm) compared to 67.8% of Dutch controls (P < 0.01). Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0.01). We found reduced general subjective health-related QoL scores in both male and female patients, especially in younger patients <65 years of age. CONCLUSION: Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue. more...

Contains fulltext : 171585.pdf (publisher's version ) (Closed access), Adrenal Cortical Carcinoma (ACC) is a rare malignancy with an incidence of 1.0 per million per year in the Netherlands. Median survival varies according to the European Network for the Study of Adrenal Tumours (ENS@T) tumour stage. It is unknown whether time until development of metastases is of influence on prognosis. To asses this, data were retrospectively obtained from centres of the Dutch Adrenal Network. Patients who presented with ACC between January 1, 2004 and October 31, 2013 were included. Date of detection of metastases, number of metastases and affected organs were registered. One hundred sixty patients were included in the analysis. Synchronous metastases were defined as diagnosis of metastasis more...

Contains fulltext : 172795.pdf (publisher's version ) (Closed access), BACKGROUND: An adrenal crisis (AC) is a potential life-threatening event in patients with adrenal insufficiency (AI). This study aims to determine the incidence, causes, and risk factors of AC in AI. METHODS: Patients with AI diagnosed and treated at the University Medical Center Utrecht for the past 30 years were identified, and all medical records were assessed by two independent investigators. The observed frequency of AC was determined as incidence rate, calculated as the number of AC divided by person-years (PY). In addition, precipitating factors and risk factors were assessed. Results : We observed an incidence rate of 5.2 AC (95% CI 4.3-6.3) per 100 PY in primary adrenal insufficiency (PAI, a total of 111 patients), and 3.6 AC (95% CI 3.1-4.1) per 100 PY in secondary adrenal insufficiency (SAI a total of 319 patients). Patients with an established diagnosis of tertiary (glucocorticoid-induced) adrenal insufficiency (a total of 28 patients) had 15.1 AC (95% CI 11.0-19.9) per 100 PY. The most important risk factor was the existence of comorbidity. Gastro-enteritis and other infections were the most common precipitating factors for AC. CONCLUSION: AC still occurs relatively frequent in patients with AI, mostly precipitated by infections and particularly in patients with high comorbidity. This should be taken into account in the education and follow-up of patients with AI. more...

Item does not contain fulltext, OBJECTIVE/METHODS: Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that stepwise medical combination therapy with the somatostatin-analog pasireotide, the dopamine-agonist cabergoline, and ketoconazole (which directly suppresses steroidogenesis) biochemically controlled CD patients and lowered their blood pressure after 80 days. Glucocorticoids (GC) modulate the renin-angiotensin-aldosterone system (RAAS) among others by increasing hepatic angiotensinogen expression and stimulating mineralocorticoid receptors (MR). This study therefore evaluated plasma RAAS components in CD patients before and after drug therapy. In addition, we studied whether cabergoline/pasireotide have direct relaxant effects in angiotensin II (Ang II)-constricted iliac arteries of spontaneously hypertensive rats, with and without concomitant GR/MR stimulation with dexamethasone or hydrocortisone. RESULTS: Baseline concentrations of angiotensinogen were elevated, while renin and aldosterone were low and suppressed, respectively, even in patients treated with RAAS-blockers. This pattern did not change after 80 days of treatment, despite blood pressure normalization, nor after 4 years of remission. In the presence of dexamethasone, pasireotide inhibited Ang II-mediated vasoconstriction. CONCLUSIONS: The low plasma renin concentrations, even under RAAS blockade, in CD may be the consequence of increased GC-mediated MR stimulation and/or the elevated angiotensinogen levels in such patients. The lack of change in RAAS-parameters despite blood pressure and cortisol normalization suggests persisting consequences of long-term exposure to cortisol excess. Finally, pasireotide may have a direct vasodilating effect contributing to blood pressure lowering. more...

1 december 2013, Item does not contain fulltext, Cushing's disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17 patients, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. After 80 days, 15/17 (88%) patients had reached normal urinary free cortisol excretion (UFC). Subsequently, patients continued medical therapy or underwent surgery. UFC, plasma and salivary CDR and QoL-related parameters (assessed using 5 questionnaires: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index-20, RAND-36, CushingQoL) were measured. At baseline, 5/17 patients had preserved CDR. In 6/12 patients with disturbed baseline CDR, recovery was observed, but without any correlation with QoL. QoL was significantly impaired according to 18/20 subscales in CD patients compared to literature-derived controls. According to the RAND-36 questionnaire, patients reported more pain at day 80 (p < 0.05), which might reflect steroid-withdrawal. Generally, QoL did not improve or deteriorate after 80 days. CushingQoL scores seemed to improve after 1 year of remission in three patients that continued medical therapy (p = 0.11). CDR can recover during successful pituitary- and adrenal-targeted medical therapy. Patients with CD have impaired QoL compared to controls. Despite the occurrence of side-effects, QoL does not deteriorate after short-term biochemical remission induced by medical therapy, but might improve after sustained control of hypercortisolism. more...

Item does not contain fulltext, OBJECTIVE: Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects. The aim of this study was to investigate the use of salivary cortisol day curves (SCDC) in the individual adjustment of GRT in order to approach normal cortisol levels as closely as possible, reduce over- and underreplacement and study the short-term effects on quality of life (QoL). DESIGN AND METHODS: Twenty patients with Addison's disease were included in this prospective study. A SCDC was obtained and compared to normal controls; general and disease specific QoL-questionnaires were completed. Based on SCDC assessment of over- and undertreatment (calculated as duration (h) x magnitude (nmol/L) at different time points, glucocorticoid dose and regime were adjusted. After 4 weeks SCDC and QoL assessment were repeated and the effect of adjusting GRT was analysed. RESULTS: At baseline, underreplacement was present in 3 and overreplacement in 18 patients; total calculated overreplacement was 32.8 h.nmol/L. Overreplacement decreased significantly to 13.3 h. nmol/L (p =0.005) after adjustment of GRT. Overreplacement was found particularly in the afternoon and evening. After reducing overreplacement in the evening, complaints about sleep disturbances significantly decreased. CONCLUSIONS: Individual adjustment of GRT based on SCDC to approach normal cortisol concentrations during the day can reduce overreplacement, especially in the evening. This can lead to a reduction of sleep disturbances and fatigue in patients with Addison's disease. A SCDC is a simple and patient-friendly tool for adjusting GRT and can be useful in the follow-up of patients with Addison's disease. more...

1 april 2012, Item does not contain fulltext, CONTEXT: Cushing's disease (CD) is accompanied by an increased risk of venous thromboembolism. Surgery is the primary treatment of CD. OBJECTIVE: The aim of the study was to compare hemostatic parameters between patients with CD and controls and to evaluate the effect of medical treatment of CD on hemostasis. DESIGN AND SETTING: During 80 d, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline, and ketoconazole, which suppresses adrenocortical steroidogenesis, at four university medical centers in The Netherlands. PATIENTS: Seventeen patients with de novo, residual, or recurrent CD were included. MAIN OUTCOME MEASURES: We measured urinary free cortisol and parameters of coagulation and fibrinolysis. RESULTS: Patients with CD had significantly higher body mass index (P < 0.001), shortened activated partial thromboplastin time (P < 0.01), and higher levels of fibrinogen, Factor VIII, and protein S activity (P < 0.05) compared to healthy control subjects. In addition, fibrinolytic capacity was impaired in patients with CD as reflected by prolonged clot lysis time (P < 0.001) and higher levels of plasminogen activator inhibitor type 1, thrombin-activatable fibrinolysis inhibitor, and alpha2-antiplasmin (P < 0.01). There were no statistically significant differences in von Willebrand factor:antigen, antithrombin, and protein C activity. After 80 d, 15 of 17 patients had normalized urinary free cortisol excretion. Despite biochemical remission, only slight decreases in antithrombin (P < 0.01) and thrombin-activatable fibrinolysis inhibitor (P < 0.05) levels were observed. Other parameters of coagulation and fibrinolysis did not change significantly. CONCLUSIONS: The hypercoagulable state in patients with CD, which is explained by both increased production of procoagulant factors and impaired fibrinolysis, is not reversible upon short-term biochemical remission after successful medical therapy. This may have impl more...

Contains fulltext : 97999.pdf (publisher's version ) (Closed access), Context: Venous thrombosis has frequently been reported in patients with endogenous Cushing's syndrome (CS). Objective: The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with CS prior to treatment and after surgery. Design and Setting: We conducted a multicenter cohort study at all university medical centers in The Netherlands. Patients: Consecutive patients diagnosed with endogenous CS of benign origin between January 1990 and June 2010 were eligible for inclusion. Patients surgically treated for nonfunctioning pituitary adenoma served as controls for the incidence of postoperative VTE in ACTH-dependent CS. Main Outcome Measures: We documented all objectively confirmed VTE during 3 yr prior to, and 3 yr after treatment onset. The incidences of VTE were expressed as incidence rates. Results: A total of 473 patients (mean age 42 yr, 363 women) were included (360 ACTH-dependent pituitary CS). The total number of person-years was 2526. Thirty-seven patients experienced VTE during the study period, resulting in an incidence rate of 14.6 [95% confidence interval (CI) 10.3-20.1] per 1000 person-years. The incidence rate for first-ever VTE prior to treatment was 12.9 (95% CI 7.5-12.6) per 1000 person-years (17 events). The risk of postoperative VTE, defined as risk within 3 months after surgery, was 0% for ACTH-independent and 3.4% (95% CI 2.0-5.9) for ACTH-dependent CS (12 events in 350 patients); most events occurred between 1 wk and 2 months after surgery. Compared with the controls, the risk of postoperative VTE in patients undergoing transsphenoidal surgery was significantly greater (P = 0.01). Conclusions: Patients with CS are at high risk of VTE, especially during active disease and after pituitary surgery. Guidelines on thromboprophylaxis are urgently needed. more...

Contains fulltext : 89845.pdf (publisher's version ) (Open Access)

Contains fulltext : 56140.pdf (publisher's version ) (Closed access), The objective of this study was to examine whether beliefs about the cause, consequences, time line, and control of obesity are predictors of the amount of weight loss after an 8-week, low-calorie diet consisting of meal replacements. Forty-eight women and 18 men, mean age=45.9 (range=23 to 73 years) years and body mass index between 30 and 50 participated in a weight-loss program. Beliefs were measured at baseline by the Obesity Cognition Questionnaire and by an eating behavior self-efficacy scale. Correlational and regression analyses were performed to examine whether beliefs predicted weight change. Changes in body mass index, waist circumference, and blood pressure were significant (P<.001). Less weight reduction was associated with poor self-efficacy (r=−0.34, P<.01) and the beliefs that obesity had a physical origin (r=0.27, P=.04) and was not under behavioral control (r=−0.25, P=.04). Self-efficacy remained a significant predictor in regression analysis. The results suggest that the outcome of dietary interventions may be improved when adjusting beliefs, especially self-efficacy. more...

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