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Jitske Tiemensma, Cornelie D Andela, Ad A Kaptein, Johannes A Romijn, Roos C van der Mast, Nienke R Biermasz and Alberto M Pereira

Context

A high prevalence of psychological morbidity and maladaptive personality as well as impaired quality of life (QoL) is observed in patients with and without hydrocortisone dependency following (cured) Cushing's syndrome. However, it is currently unclear whether a similar pattern is present in patients with chronic glucocorticoid replacement for primary adrenal insufficiency (PAI).

Objective

To evaluate psychological functioning, personality traits, and QoL in patients with PAI.

Design and subjects

A cross-sectional study including 54 patients with stable treatment for PAI and 54 healthy matched controls. Both patients and controls completed questionnaires on psychological functioning (Apathy Scale, Irritability Scale, Mood and Anxiety Symptoms Questionnaire short form, and Hospital Anxiety and Depression Scale), personality traits (Dimensional Assessment of Personality Pathology short form), and QoL (Multidimensional Fatigue Inventory, Short Form 36, EuroQoL-5D, Nottingham Health Profile, and Physical Symptom Checklist).

Results

Patients with PAI suffered from more psychological morbidity (i.e. irritability and somatic arousal) and QoL impairments compared with controls (all P<0.01). There were no differences regarding maladaptive personality traits between patients and controls. However, there was a strong and consistent positive association between the daily hydrocortisone dose and prevalence of maladaptive personality traits (i.e. identity problems, cognitive distortion, compulsivity, restricted expression, callousness, oppositionality, rejection, conduct problems, social avoidance, narcissism, and insecure attachment, all P<0.05). There was also a strong relation between the mean daily hydrocortisone dose and both psychological morbidity (i.e. depression, P<0.05) and QoL impairments (i.e. general health perception, several measures of physical functioning, and vitality, all P<0.05).

Conclusion

Patients on stable glucocorticoid replacement therapy for PAI report psychological morbidity and impaired QoL. Psychological morbidity, impaired QoL, and maladaptive personality traits were all associated with higher dosages of hydrocortisone.

Free access

Cornelie D Andela, Han Repping-Wuts, Nike M M L Stikkelbroeck, Mathilde C Pronk, Jitske Tiemensma, Ad R Hermus, Adrian A Kaptein, Alberto M Pereira, Noelle G A Kamminga and Nienke R Biermasz

Context

Patients with pituitary disease report impairments in Quality of Life (QoL) despite optimal biomedical care. Until now, the effects of a self-management intervention (SMI) addressing psychological and social issues for these patients and their partners have not been studied.

Objective

To examine the effects of a SMI i.e. Patient and Partner Education Programme for Pituitary disease (PPEP-Pituitary).

Design and subjects

A multicentre randomized controlled trial included 174 patients with pituitary disease, and 63 partners were allocated to either PPEP-Pituitary or a control group. PPEP-Pituitary included eight weekly sessions (90 min). Self-efficacy, bother and needs for support, illness perceptions, coping and QoL were assessed before the intervention (T0), directly after (T1) and after six months (T2). Mood was assessed before and after each session.

Results

Patients in PPEP-Pituitary reported improved mood after each session (except for session 1). In partners, mood only improved after the last three sessions. Patients reported higher self-efficacy at T1 (P = 0.016) which persisted up to T2 (P = 0.033), and less bother by mood problems directly after PPEP-Pituitary (P = 0.01), but more bother after six months (P = 0.001), although this increase was not different from baseline (P = 0.346). Partners in PPEP-Pituitary reported more vitality (P = 0.008) which persisted up to T2 (P = 0.034). At T2, partners also reported less anxiety and depressive symptoms (P ≤ 0.014).

Conclusion

This first study evaluating the effects of a SMI targeting psychosocial issues in patients with pituitary disease and their partners demonstrated promising positive results. Future research should focus on the refinement and implementation of this SMI into clinical practice.

Free access

Cornelie D Andela, Femke M van Haalen, Oskar Ragnarsson, Eleni Papakokkinou, Gudmundur Johannsson, Alicia Santos, Susan M Webb, Nienke R Biermasz, Nic J A van der Wee and Alberto M Pereira

Background

Cushing's syndrome (CS) is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids.

Objective

To review publications evaluating brain characteristics in patients with CS using magnetic resonance imaging (MRI).

Methods

Systematic review of literature published in PubMed, Embase, Web of Knowledge, and Cochrane databases.

Results

Nineteen studies using MRI in patients with CS were selected, including studies in patients with active disease, patients in long-term remission, and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e., cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life).

Conclusion

Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.

Free access

Cornelie D Andela, Steven J A van der Werff, J Nienke Pannekoek, Susan M van den Berg, Onno C Meijer, Mark A van Buchem, Serge A R B Rombouts, Roos C van der Mast, Johannes A Romijn, Jitske Tiemensma, Nienke R Biermasz, Nic J A van der Wee and Alberto M Pereira

Objective

Patients with long-term remission of Cushing's disease (CD) have persistent psychological and cognitive impairments. It is unknown whether, and to what extent, these impairments are accompanied by structural abnormalities in the brain. We aim to investigate structural changes in the brain in patients with predominantly long-term remission of CD and to examine whether these changes are associated with psychological and cognitive dysfunction and clinical severity.

Design

A cross-sectional, case–control study.

Methods

In 25 patients with predominantly long-term remission of CD and 25 matched healthy controls, grey matter volumes in the regions of interest (hippocampus, amygdala, and anterior cingulate cortex (ACC)) and in the whole brain were examined, using 3T magnetic resonance imaging and a voxel-based morphometry approach. Psychological and cognitive functioning were assessed using validated questionnaires and clinical severity was assessed using the Cushing's syndrome severity index.

Results

Compared with controls, patients had smaller grey matter volumes of areas in the ACC (on average 14%, P<0.05) and greater volume of the left posterior lobe of the cerebellum (on average 34%, P<0.05). As expected, patients with remitted CD reported more depressive symptoms (P=0.005), more anxiety (P=0.003), more social phobia (P=0.034), more apathy (P=0.002), and more cognitive failure (P=0.023) compared with controls, but the differences in grey matter volumes were not associated with psychological or cognitive measures, nor with clinical severity.

Conclusion

Patients with predominantly long-term remission of CD showed specific structural brain abnormalities, in the presence of psychological dysfunction. Our data form a basis for future work aimed at elucidating the relation of the structural brain abnormalities and the sustained psychological deficits after long-term exposure to high cortisol levels.

Restricted access

Daniel J Lobatto, Amir H Zamanipoor Najafabadi, Friso de Vries, Cornelie D Andela, Wilbert B van den Hout, Alberto M Pereira, Wilco C Peul, Thea P M Vliet Vlieland, Wouter R van Furth and Nienke R Biermasz

Objective

Although widely advocated, applying Value Based Health Care (VBHC) in clinical practice is challenging. This study describes VBHC-based perioperative outcomes for patients with pituitary tumors up to 6 months postoperatively.

Methods

A total of 103 adult patients undergoing surgery were prospectively followed. Outcomes categorized according to the framework of VHBC included survival, degree of resection, endocrine remission, visual outcome (including self-perceived functioning), recovery of pituitary function, disease burden and health-related quality of life (HRQoL) at 6 months (Tier 1); time to recovery of disease burden, HRQoL, visual function (Tier 2); permanent hypopituitarism and accompanying hormone replacement (Tier 3). Generalized estimating equations (GEEs) analysis was performed to describe outcomes over time.

Results

Regarding Tier 1, there was no mortality, 72 patients (70%) had a complete resection, 31 of 45 patients (69%) with functioning tumors were in remission, 7 (12%, with preoperative deficits) had recovery of pituitary function and 45 of 47 (96%) had visual improvement. Disease burden and HRQoL improved in 36–45% at 6 months; however, there were significant differences between tumor types. Regarding Tier 2: disease burden, HRQoL and visual functioning improved within 6 weeks after surgery; however, recovery varied widely among tumor types (fastest in prolactinoma and non-functioning adenoma patients). Regarding Tier 3, 52 patients (50%) had persisting (tumor and treatment-induced) hypopituitarism.

Conclusions

Though challenging, outcomes of a surgical intervention for patients with pituitary tumors can be reflected through a VBHC-based comprehensive outcome set that can distinguish outcomes among different patient groups with respect to tumor type.