Background. Growth-hormone-producing pituitary adenomas have variable likelihood for biochemical remission (BR). During preoperative counseling, individual estimated surgical likelihoods/risks... Show moreBackground. Growth-hormone-producing pituitary adenomas have variable likelihood for biochemical remission (BR). During preoperative counseling, individual estimated surgical likelihoods/risks should be balanced against alternative (medical) treatments, which is necessary for accurate outcome presentation. Preoperative estimation of BR or total resection (TR) likelihoods have not been reported, resulting in extrapolation of individual outcomes. Aims. To share an innovative outcome reporting paradigm by integrating surgical decision-making, and expected/realized results, resulting from the Value-Based Health Care (VBHC) care path with periodical performance evaluation and care innovation cycle. Methods. Prospective cohort study of consecutive patients with acromegaly undergoing surgery (January 2016-December 2020; postoperative follow-up >= 6 months) reporting on both classic, and novel innovative outcome evaluations. Results. Fifty eight patients (66 procedures) were included. Intended TR was achieved in 34/50 procedures, whereas intended debulking was achieved in 15/16 procedures. 38/66 procedures resulted in BR, and 4 procedures resulted in permanent complications. Achieving intended surgical goal was estimated preoperatively as likely in 33 (goal achieved (GA) in 28/33), potentially in 27 (GA in 19/27), and unlikely in 6 procedures (GA in 2/6). Integrated Outcome Square 1 (IOQ1) -intended effect achieved without complications- was achieved in 46/66 patients. Conclusion. Implementation of the developed quality process positively affects preopparticularly in complex patients for whom preoperative chances are not fully reflected by tumor size and KNOSP grade, e.g., reoperations, or other challenging circumstances identified during preoperative counseling. Through repeated evaluations, our own team's reserved. Show less
Koning, A.S.C.A.M.; Meulen, M. van der; Schaap, D.; Satoer, D.D.; Vinkers, C.H.; Rossum, E.F.C. van; ... ; Dekkers, O.M. 2023
Context Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric adverse effects... Show moreContext Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric adverse effects.Objective This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids.Methods Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort studies, and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and nonusers were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model.Results We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95% CI, 14%-33%), 11% for mania (2%-46%), 8% for anxiety (2%-25%), 16% for delirium (6%-36%), and 52% for behavioral changes (42%-61%). Questionnaire scores for depression (SMD of 0.80 [95% CI 0.35-1.26]), and mania (0.78 [0.14-1.42]) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use.Conclusion The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed. Show less
PurposeTo describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery.MethodsRetrospective observational cohort study of consecutive patients with... Show morePurposeTo describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery.MethodsRetrospective observational cohort study of consecutive patients with prolactinoma undergoing surgery from 2017 to 2019 at the referral center (RC), prior to surgery being considered a viable treatment option (i.e. PRolaCT study). Demographics and clinical data (type and duration of pretreatment and surgical indications, goals, and outcomes) were collected from patient records. Care trajectories were divided into three phases: (1) diagnosis and initial treatment, (2) endocrine treatment at the RC, and (3) surgical treatment.Results40 patients were included (31 females (77.5%), median age 26.5 (14-63) years. Indications for surgery were dopamine agonist (DA) intolerance (n = 31, 77.5%), resistance (n = 6, 15.0%), and patient/physician preference (n = 3, 7.5%). Patients were pretreated with DA (n = 39 (97.5%)), and surgery (n = 3 (7.5%)). Median disease duration at surgery was 4 (0-27) years. Primary surgical goal was total resection in 38 patients (95.0%), of which biochemical remission was achieved 6 months postoperatively in 23 patients (62.2%), and clinical remission in 6 patients (16.2%), missing data n = 1.ConclusionCare trajectories were highly individualized based on patient and tumor characteristics, as well as the multidisciplinary team's assessment (need for alternative treatment, surgical chances and risks). Most patients were pretreated pharmacologically and had broad variation in timing of referral, undergoing surgery as last-resort treatment predominantly due to DA intolerance. High quality imaging and multidisciplinary consultations with experienced neurosurgeons and endocrinologists enabling treatment tailored to patients' needs were prerequisites for adequate counseling in treatment of patients with prolactinoma. Show less
PurposeTo describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery.MethodsRetrospective observational cohort study of consecutive patients with... Show morePurposeTo describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery.MethodsRetrospective observational cohort study of consecutive patients with prolactinoma undergoing surgery from 2017 to 2019 at the referral center (RC), prior to surgery being considered a viable treatment option (i.e. PRolaCT study). Demographics and clinical data (type and duration of pretreatment and surgical indications, goals, and outcomes) were collected from patient records. Care trajectories were divided into three phases: (1) diagnosis and initial treatment, (2) endocrine treatment at the RC, and (3) surgical treatment.Results40 patients were included (31 females (77.5%), median age 26.5 (14-63) years. Indications for surgery were dopamine agonist (DA) intolerance (n = 31, 77.5%), resistance (n = 6, 15.0%), and patient/physician preference (n = 3, 7.5%). Patients were pretreated with DA (n = 39 (97.5%)), and surgery (n = 3 (7.5%)). Median disease duration at surgery was 4 (0-27) years. Primary surgical goal was total resection in 38 patients (95.0%), of which biochemical remission was achieved 6 months postoperatively in 23 patients (62.2%), and clinical remission in 6 patients (16.2%), missing data n = 1.ConclusionCare trajectories were highly individualized based on patient and tumor characteristics, as well as the multidisciplinary team's assessment (need for alternative treatment, surgical chances and risks). Most patients were pretreated pharmacologically and had broad variation in timing of referral, undergoing surgery as last-resort treatment predominantly due to DA intolerance. High quality imaging and multidisciplinary consultations with experienced neurosurgeons and endocrinologists enabling treatment tailored to patients' needs were prerequisites for adequate counseling in treatment of patients with prolactinoma. Show less
Objectives To explore the perceptions and experiences of patients who underwent transsphenoidal pituitary gland and (para)sellar tumour surgery regarding indwelling urinary catheters (IDUCs) and... Show moreObjectives To explore the perceptions and experiences of patients who underwent transsphenoidal pituitary gland and (para)sellar tumour surgery regarding indwelling urinary catheters (IDUCs) and the postoperative fluid balance.Design Qualitative study using semistructured interviews based on the attitudes, social influence and self-efficacy model and expert knowledge.Participants Twelve patients who underwent transsphenoidal pituitary gland tumour surgery and received an IDUC during or after surgery.Setting One patient was interviewed in the endocrinology outpatient clinic and 11 patients were interviewed on the neurosurgery ward.Results Five major themes emerged: (1) conflicting information and preoperative expectations, (2) IDUCs perceived as patient-friendly during bedrest, particularly for women, (3) little room for patients' opinions, (4) physical and emotional limitations and (5) fluid balance causes confusion. Information regarding IDUC placement and fluid balance given to patients both preoperatively and postoperatively did not meet their expectations, which led to confusion and uncertainty. The IDUC was perceived as preferable if bedrest was mandatory, preferred particularly by women. Patient could not mobilise freely due to the IDUC and felt ashamed, judged by others and dependent on nurses.Conclusions This study provides insight into the challenges patients experience in relation to the IDUC and fluid balance. Perceptions on the necessity of an IDUC varied among patients and were influenced by both physical and emotional impediments. A clear, frequent and daily communication between healthcare professionals and patients to evaluate IDUC and fluid balance use is necessary to increase patient satisfaction. Show less
Quach, K.T.; Dirven, L.; Vingerhoed, A.M.; Bresser, J. de; Dammers, R.; Bos, E.M.; ... ; Furth, W.R. van 2023
Background Fatigue is a commonly reported and severe symptom in primary brain tumor patients, but the exact occurrence in meningioma patients is unknown. This study aimed to determine the frequency... Show moreBackground Fatigue is a commonly reported and severe symptom in primary brain tumor patients, but the exact occurrence in meningioma patients is unknown. This study aimed to determine the frequency and severity of fatigue in meningioma patients as well as associations between the level of fatigue and patient-, tumor-, and treatment-related factors. Methods In this multicenter cross-sectional study, meningioma patients completed questionnaires on fatigue (MFI-20), sleep (PSQI), anxiety and depression (HADS), tumor-related symptoms (MDASI-BT), and cognitive functioning (MOS-CFS). Multivariable regression models were used to evaluate the independent association between fatigue and each patient-, tumor-, and treatment-related factor separately, corrected for relevant confounders. Results Based on predetermined in- and exclusion criteria, 275 patients, on average 5.3 (SD = 2.0) year since diagnosis, were recruited. Most patients had undergone resection (92%). Meningioma patients reported higher scores on all fatigue subscales compared to normative data and 26% were classified as fatigued. Having experienced a complication due to resection (OR 3.6, 95% CI: 1.8-7.0), having received radiotherapy (OR 2.4, 95% CI: 1.2-4.8), a higher number of comorbidities (OR 1.6, 95% CI: 1.3-1.9) and lower educational level (low level as reference; high level OR 0.3, 95% CI: 0.2-0.7) were independently associated with more fatigue. Conclusions Fatigue is a frequent problem in meningioma patients even many years after treatment. Both patient- and treatment-related factors were determinants of fatigue, with the treatment-related factors being the most likely target for intervention in this patient population. Show less
Najafabadi, A.H.Z.; Meulen, M. van der; Zurita, A.L.P.; Ahmed, S.F.; Furth, W.R. van; Charmandari, E.; ... ; Biermasz, N.R. 2023
ObjectiveThe European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, including care for pituitary adenoma patients. As surgery... Show moreObjectiveThe European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, including care for pituitary adenoma patients. As surgery is the mainstay of treatment, we aimed to describe the current surgical practice and published surgical outcomes of pituitary adenoma within Endo-ERN. Design and MethodsSystematic review and meta-analysis of studies reporting surgical outcomes of pituitary adenoma patients within Endo-ERN MTG6 pituitary reference centers between 2010 and 2019. A survey was completed by reference centers on their current surgical practice. Results A total of 18 out of 43 (42%) reference centers located in 7 of the 20 (35%) MTG6-represented countries published 48 articles. Remission rates were 50% (95% CI: 42-59) for patients with acromegaly, 68% (95% CI: 60-75) for Cushing's disease, and 53% (95% CI: 39-66%) for prolactinoma. Gross total resection was achieved in 49% (95% CI: 37-61%) of patients and visual improvement in 78% (95% CI: 68-87). Mortality, hemorrhage, and carotid injury occurred in less than 1% of patients. New-onset hypopituitarism occurred in 16% (95% CI: 11-23), transient diabetes insipidus in 12% (95% CI: 6-21), permanent diabetes insipidus in 4% (95% CI: 3-6), syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 9% (95% CI: 5-14), severe epistaxis in 2% (95% CI: 0-4), and cerebrospinal fluid leak in 4% (95% CI: 2-6). Thirty-five (81%) centers completed the survey: 54% were operated endoscopically and 57% were together with an ENT surgeon. ConclusionThe results of this study could be used as a first benchmark for the outcomes of pituitary adenoma surgery within Endo-ERN. However, the heterogeneity between studies in the reporting of outcomes hampers comparability and warrants outcome collection through registries. Show less
Dekkers, A.J.; Vries, F. de; Najafabadi, A.Z.H.; Hoeven, E.M. van der; Verstegen, M.J.T.; Pereira, A.M.; ... ; Biermasz, N.R. 2022
Purpose: Value-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice... Show morePurpose: Value-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice we evaluated healthcare costs and cost drivers in perioperative care for pituitary tumour patients. Methods: We retrospectively assessed financial and clinical data for surgical treatment up to the first year after surgery of pituitary tumour patients treated between 2015 and 2018 in a Dutch tertiary referral centre. Multivariable regression analyses were performed to identify determinants of higher costs. Results: 271 patients who underwent surgery were included. Mean total costs (SD) were euro16339 (13573) per patient, with the following cost determinants: surgery time (euro62 per minute; 95% CI: 50, 74), length of stay (euro1331 per day; 95% CI 1139, 1523), admission to higher care unit (euro12154 in total; 95% CI 6413, 17895), emergency surgery (euro10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (euro14232; 95% CI 9667, 18797). Intradural (euro7128; 95% CI 10421, 23836) and combined transsphenoidal/transcranial surgery (B: 38494; 95% CI 29191, 47797) were associated with higher costs than standard. Further, higher costs were found in these baseline conditions: Rathke's cleft cyst (euro9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (euro19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (euro14613; 95% CI 7613, 21613) and dependent functional status (euro12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were euro8879 (3210) and with complications euro17551 (14250). Conclusions: Length of hospital stay, and complications are the main drivers of costs in perioperative pituitary tumour healthcare as were some baseline features, e.g. larger tumors, cysts and dependent functional status. Costs analysis may correspond with healthcare resource utilization and guide further individualized care path development and capacity planning. Show less
Background Indwelling urinary catheters (IDUCs) are associated with complications and early removal is therefore essential. Currently, it is unknown what the effect of a specific removal time is... Show moreBackground Indwelling urinary catheters (IDUCs) are associated with complications and early removal is therefore essential. Currently, it is unknown what the effect of a specific removal time is and what the consequences of this removal time are. Research question To present an overview of the available evidence to determine the effects of three postoperative IDUC removal times (after a certain number of hours, at a specific time of day and flexible removal time) on the development of complications in hospital. Methods PubMed, Medline, Embase, Emcare and Cochrane Central Register of Controlled Trials were searched till 6 June, 2021. Studies were included that described the effect of the removal time in relation to re-catheterisation, urinary tract infections (UTIs), ambulation time, time of first voiding and hospital stay. The quality of the studies was assessed with the Newcastle-Ottawa Scale and the Cochrane Effective Practice and Organisation of Care. A narrative descriptive analysis was performed. PRISMA guidelines were followed in reporting this review. Results Twenty studies were included from which 18 compared removal after a number of hours, 1 reported on a specific removal time and 1 reported on both topics. The results were contradicting regarding the hypothesis that later removal increases the incidence of UTIs. Earlier removal does not lead to a higher re-catheterisation rate while immediate removal is beneficial for reducing the time to first ambulation and shortening the hospital stay. Studies reporting on specific removal times did not find differences in outcomes. No study addressed flexible removal time. Conclusions There is inconclusive evidence that earlier removal results in less UTIs, despite the incidence of UTIs increasing if the IDUC is removed >= 24 h. Immediate or after 1-2 day(s) removal does not lead to higher re-catheterisation rates while immediate removal results in earlier ambulation and shorter length of hospital stay. Implications of key findings Nurses should focus on early IDUC removal while being aware of urinary retention. Show less
Purpose: To report the first experience of our multidisciplinary team with functional imaging using C-11-methionine positron emission tomography-computed tomography (C-11-methionine PET-CT) co... Show morePurpose: To report the first experience of our multidisciplinary team with functional imaging using C-11-methionine positron emission tomography-computed tomography (C-11-methionine PET-CT) co-registered with MRI (Met-PET/MRICR) in clinical decision making and surgical planning of patients with difficult to treat prolactinoma. Methods: In eighteen patients with prolactinoma, referred to our tertiary referral centre because of intolerance or resistance for dopamine agonists (DA), Met-PET/MRICR was used to aid decision-making regarding therapy. Results: Met-PET/MRICR was positive in 94% of the patients. MRI and Met-PET/MRICR findings were completely concordant in five patients, partially concordant in nine patients, and non-concordant in four patients. In five patients Met-PET/MRICR identified lesion(s) that were retrospectively also visible on MRI. Met-PET/MRICR was false negative in one patient, with a cystic adenoma on conventional MRI. Thirteen patients underwent transsphenoidal surgery, with nine achieving full biochemical remission, two clinical improvement and near normalized prolactin levels, and one patient clinical improvement with significant tumour reduction. Hence, nearly all patients (94%) were considered to have a positive outcome. Permanent complication rate was low. Three patients continued DA, two patients have a wait and scan policy. Conclusion: Met-PET/MRICR can provide additional information to guide multidisciplinary preoperative and intraoperative decision making in selected cases of prolactinoma. This approach resulted in a high remission rate with a low rate of complications in our expert centre. Show less
Fisher, F.L.; Najafabadi, A.H.Z.; Meer, P.B. van der; Boele, F.W.; Peerdeman, S.M.; Peul, W.C.; ... ; Furth, W.R. van 2022
OBJECTIVE Patients with skull base meningioma (SBM) often require complex surgery around critical neurovascular structures, placing them at high risk of poor health-related quality of life (HRQOL)... Show moreOBJECTIVE Patients with skull base meningioma (SBM) often require complex surgery around critical neurovascular structures, placing them at high risk of poor health-related quality of life (HRQOL) and possibly neurocognitive dysfunction. As the survival of meningioma patients is near normal, long-term neurocognitive and HRQOL outcomes are important to evaluate, including evaluation of the impact of specific tumor location and treatment modalities on these outcomes. METHODS In this multicenter cross-sectional study including patients 5 years or more after their last tumor intervention, Short-Form Health Survey (SF-36) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-BN20 questionnaires were used to assess generic and disease-specific HRQOL. Neurocognitive functioning was assessed with standardized neuropsychological assessment. SBM patient assessments were compared with those of 1) informal caregivers of SBM patients who served as controls and 2) convexity meningioma patients. In addition, the authors compared anterior/middle SBM patients with posterior SBM patients and anterior/middle and posterior SBM patients separately with controls. Multivariable and propensity score regression analyses were performed to correct for possible confounders. RESULTS Patients with SBM (n = 89) with a median follow-up of 9 years after the last intervention did not significantly differ from controls (n = 65) or convexity meningioma patients (n = 84) on generic HRQOL assessment. Statistically significantly but not clinically relevantly better disease-specific HRQOL was found for SBM patients compared with convexity meningioma patients. Anterior/middle SBM patients (n = 62) had significantly and clinically relevantly better HRQOL in SF-36 and EORTC QLQ-BN20 scores than posterior SBM patients (n = 27): physical role functioning (corrected difference 17.1, 95% CI 0.2-34.0), motor dysfunction (-10.1, 95% CI -17.5 to -2.7), communication deficit (-14.2, 95% CI -22.7 to -5.6), and weakness in both legs (-10.1, 95% CI -18.8 to -1.5). SBM patients whose primary treatment was radiotherapy had lower HRQOL scores compared with SBM patients who underwent surgery on two domains: bodily pain (-33.0, 95% CI -55.2 to -10.9) and vitality (-18.9. 95% CI -33.7 to -4.1). Tumor location and treatment modality did not result in significant differences in neurocognitive functioning, although 44% of SBM patients had deficits in at least one domain. CONCLUSIONS In the long term, SBM patients do not experience significantly more sequelae in HRQOL and neurocognitive functioning than do controls or patients with convexity meningioma. Patients with posterior SBM had poorer HRQOL than anterior/middle SBM patients, and primary treatment with radiotherapy was associated with worse HRQOL. Neurocognitive functioning was not affected by tumor location or treatment modality. Show less
Purpose The condition of pituitary apoplexia contains the clinical spectre from life-threatening emergency to asymptomatic self-limiting course, which partly determines diagnostic delay and... Show morePurpose The condition of pituitary apoplexia contains the clinical spectre from life-threatening emergency to asymptomatic self-limiting course, which partly determines diagnostic delay and management. Outcome evaluation of course and management of pituitary apoplexia is hampered by the diverse presentation of this condition and requires appraisal. This study aimed to describe the patient journey, clinical presentation, and management of various types of pituitary apoplexy in a new classification to facilitate future outcome evaluation and identify unmet needs in the care process. Methods A single-center retrospective patient chart study was conducted between 2005-2021 (N = 98). Outcome measures were clinical symptoms at first presentation in hospital, being headache, consciousness, visual acuity, visual field defects (VFD), ophthalmoplegia, nausea, vomiting, fever, and hypopituitarism and care process characteristics. Results Mean age was 47.6 +/- 16.6 years (51.0% male). We describe their patient journey and identified three different types, differing in clinical presentation, in-hospital route, and final treatment, e.g., Acute (type A, 52%), Subacute (type B, 22.5%), and Non-acute (type C, 25.5%). Type A generally presents with acute onset headaches, VFD, or ophthalmoplegia emergency setting, with lowest mean visual acuity of both eyes and frequent hypocortisolism. Conclusions Pituitary apoplexy can be approached as a spectrum of disease with 3 main subtypes, with a different initial presentation, different in-hospital route resulting in different management. Acknowledging subtypes with particular needs for (emergency) referrals to Pituitary Tumors Center of Excellence (PTCOE) will serve patient care improvements, outcome evaluations and address areas for improvement. Show less
Meulen, M. van der; Verstegen, M.J.T.; Lobatto, D.J.; Kleijwegt, M.C.; Pereira, A.M.; Biermasz, N.R.; ... ; Najafabadi, A.H.Z. 2022
Purpose: Endoscopic transsphenoidal surgery causes nasal morbidity and negatively affects health-related quality of life (HRQoL). Knowledge on actionable symptoms that could improve postoperative... Show morePurpose: Endoscopic transsphenoidal surgery causes nasal morbidity and negatively affects health-related quality of life (HRQoL). Knowledge on actionable symptoms that could improve postoperative HRQoL is therefore important. This study assessed the impact of nasal symptoms on postoperative HRQoL. Methods: This perioperative cohort study included 103 adult patients undergoing endoscopic pituitary adenoma resection (August 2016-December 2018), with measurements preoperatively, and 5 days, 6 weeks and 6 months after surgery. Nasal symptoms were measured with the Anterior Skull base nasal inventory-12, and HRQoL with the Short Form-36 (SF-36) physical (PCS) and mental component scores (MCS). Linear regression analysis was used to assess (1) determinants of postoperative nasal morbidity, (2) associations between number of symptoms or (3) individual symptoms and HRQoL, and (4) the percentage of variance of HRQoL explained by nasal symptoms. Results: The number of nasal symptoms transiently increased after surgery. No significant treatment- or disease-related determinants of nasal morbidity were identified. The number of nasal symptoms was significantly associated with a lower PCS (beta = - 1.0; 95%CI - 1.5, - 0.4), but not with MCS at 6 weeks. Similar results were observed at 6 months. Headaches (42.2%), problems with smell (42.0%), and taste (36.0%) were the most prevalent symptoms, while sense of smell and taste, and nasal discharge showed the strongest associations with HRQoL. Conclusions: Postoperative nasal symptoms, in particular problems with smell and taste, significantly affect pituitary patients' physical HRQoL. Monitoring of these symptoms may aid in determining which patients may benefit from intensified follow-up and treatment, aiming to optimize HRQoL. Show less
Hypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be caused by different... Show moreHypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be caused by different pathophysiological processes, and can be isolated or the manifestation of a underlying systemic disease. Hypophysitis usually presents with endocrine deficiencies, including diabetes insipidus, with varying patterns. A subset of patients presents with mass effects. The last decades major progress has been made in the understanding of this disease. New forms are now recognized, new diagnostics are being developed, and specific treatments are proposed. This review provides an overview of the current knowledge on hypophysitis using an aetiology-based approach and provides the clinician with a stepwise approach to the patient with (suspected) hypophysitis. (C) 2021 Published by Elsevier Masson SAS. Show less
Introduction The synthetic glucocorticoid dexamethasone can induce serious neuropsychiatric adverse effects. Dexamethasone activates the glucocorticoid receptor (GR) but, unlike endogenous cortisol... Show moreIntroduction The synthetic glucocorticoid dexamethasone can induce serious neuropsychiatric adverse effects. Dexamethasone activates the glucocorticoid receptor (GR) but, unlike endogenous cortisol, not the mineralocorticoid receptor (MR). Moreover, dexamethasone suppresses cortisol production, thereby eliminating its MR binding. Consequently, GR overactivation combined with MR underactivation may contribute to the neuropsychiatric adverse effects of dexamethasone. The DEXA-CORT trial aims to reactivate the MR using cortisol to reduce neuropsychiatric adverse effects of dexamethasone treatment. Methods and analysis The DEXA-CORT study is a multicentre, randomised, double-blind, placebo-controlled trial in adult patients who undergo elective brain tumour resection treated perioperatively with high doses of dexamethasone to minimise cerebral oedema. 180 patients are randomised between treatment with either two times per day 10 mg hydrocortisone or placebo during dexamethasone treatment. The primary study outcome is the difference in proportion of patients scoring >= 3 points on at least one of the Brief Psychiatric Rating Scale (BPRS) questions 5 days postoperatively or earlier at discharge. Secondary outcomes are neuropsychiatric symptoms, quality of sleep, health-related quality of life and neurocognitive functioning at several time points postoperatively. Furthermore, neuropsychiatric history, serious adverse events, prescribed (psychiatric) medication and referrals or evaluations of psychiatrist/psychologist and laboratory measurements are assessed. Ethics and dissemination The study protocol has been approved by the Medical Research Ethics Committee of the Leiden University Medical Center, and by the Dutch competent authority, and by the Institutional Review Boards of the participating sites. It is an investigator-initiated study with financial support by The Netherlands Organisation for Health Research and Development (ZonMw) and the Dutch Brain Foundation. Results of the study will be submitted for publication in a peer-reviewed journal. Show less
Background: First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal... Show moreBackground: First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size.Methods: We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naive patients; PRolaCT-2: patients with limited duration of DA treatment (4-6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months.Discussion: Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine. Show less
Context: Transsphenoidal surgery is standard care in the treatment of hormone-secreting pituitary adenomas. Current clinician-reported surgical outcome measures are one-dimensional, typically... Show moreContext: Transsphenoidal surgery is standard care in the treatment of hormone-secreting pituitary adenomas. Current clinician-reported surgical outcome measures are one-dimensional, typically focusing primarily on complete or partial resection, and secondarily on complication rates. However, outcomes are best reflected by the delicate balance of efficacy and complications at patient level.Objective: This study proposes a novel way to classify and report outcomes, integrating efficacy and safety at the patient level.Methods: Retrospective chart review of all pure endoscopic transsphenoidal surgical procedures for acromegaly, Cushing's disease, and prolactinoma between 2010 and 2018 in a single tertiary referral center. We present our results in a classic (remission and complications separate) and in a novel outcome square integrating both outcomes, focusing on intended and adverse effects (long-term complications). This resulted in 4 outcome groups, ranging from good to poor. We use this approach to present these outcomes for several subgroups.Results: A total of 198 surgical procedures were included (44 reoperations). Remission was achieved in 127 operations (64%). Good outcome was observed after 121 (61%), and poor outcome after 6 (3%) operations. When intended effect of surgery was applied (instead of remission), good outcome as intended was achieved after 148 of 198 surgeries (75%) and poor outcome after 4 (2%).Conclusion: Quality of a surgical intervention can be presented in 4 simple categories, integrating both efficacy and safety with flexibility to adapt to the individualized situation at patient, disease, and surgical strategy and to the outcome of interest. Show less
Meulen, M. van der; Najafabadi, A.H.Z.; Broersen, L.H.A.; Schoones, J.W.; Pereira, A.M.; Furth, W.R. van; ... ; Biermasz, N.R. 2021
Purpose Postoperative cerebrospinal fluid rhinorrhoea (CSFR) remains a frequent complication of endonasal approaches to pituitary and skull base tumours. Watertight skull base reconstruction is... Show morePurpose Postoperative cerebrospinal fluid rhinorrhoea (CSFR) remains a frequent complication of endonasal approaches to pituitary and skull base tumours. Watertight skull base reconstruction is important in preventing CSFR. We sought to systematically review the current literature of available skull base repair techniques. Methods Pubmed and Embase databases were searched for studies (2000-2020) that (a) reported on the endonasal resection of pituitary and skull base tumours, (b) focussed on skull base repair techniques and/or postoperative CSFR risk factors, and (c) included CSFR data. Roles, advantages and disadvantages of each repair method were detailed. Random-effects meta-analyses were performed where possible. Results 193 studies were included. Repair methods were categorised based on function and anatomical level. There was absolute heterogeneity in repair methods used, with no independent studies sharing the same repair protocol. Techniques most commonly used for low CSFR risk cases were fat grafts, fascia lata grafts and synthetic grafts. For cases with higher CSFR risk, multilayer regimes were utilized with vascularized flaps, gasket sealing and lumbar drains. Lumbar drain use for high CSFR risk cases was supported by a randomised study (Oxford CEBM: Grade B recommendation), but otherwise there was limited high-level evidence. Pooled CSFR incidence by approach was 3.7% (CI 3-4.5%) for transsphenoidal, 9% (CI 7.2-11.3%) for expanded endonasal, and 5.3% (CI 3.4-7%) for studies describing both. Further meaningful meta-analyses of repair methods were not performed due to significant repair protocol heterogeneity. Conclusions Modern reconstructive protocols are heterogeneous and there is limited evidence to suggest the optimal repair technique after pituitary and skull base tumour resection. Further studies are needed to guide practice. Show less
