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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 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) years 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.

Objective The 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 Methods Systematic 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. Conclusion The 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.

PurposeValue-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.MethodsWe 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.Results271 patients who underwent surgery were included. Mean total costs (SD) were €16339 (13573) per patient, with the following cost determinants: surgery time (€62 per minute; 95% CI: 50, 74), length of stay (€1331 per day; 95% CI 1139, 1523), admission to higher care unit (€12154 in total; 95% CI 6413, 17895), emergency surgery (€10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (€14232; 95% CI 9667, 18797). Intradural (€7128; 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 (€9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (€19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (€14613; 95% CI 7613, 21613) and dependent functional status (€12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were €8879 (3210) and with complications €17551 (14250).ConclusionsLength 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.

Purpose The effectiveness and safety of surgery for spheno‐orbital meningiomas remains subject of debate, as studies often describe different surgical approaches and reconstruction techniques with very heterogeneous outcomes. We aimed to systematically summarize and analyse the literature on spheno‐orbital meningiomas regarding presenting symptoms, surgical techniques, outcomes and complications. Methods Studies were retrieved from eight databases. Original articles were included if in ≥5 patients presenting symptoms, surgical treatment and outcomes were described. Fixed‐ and random‐effects meta‐analysis was performed to estimate weighted percentages with 95%CIs of presenting symptoms, outcomes and complications. Results Thirty‐eight articles were included describing 1486 patients. Proptosis was the most common presenting symptom (84%; 95%CI 76–91%), followed by unilateral visual acuity deficits (46%; 95%CI 40–51%) and visual field deficits (31%; 95%CI 20–43%). In 35/38 studies (92%), a pterional craniotomy was used. Decompression of the optic canal (82%) and the superior orbital fissure (66%) was most often performed, and usually dural (47%) and bony defects (76%) were reconstructed. In almost all patients, visual acuity (91%; 95%CI 86–96%), visual fields (87%; 95%CI 70–99%) and proptosis (96%; 95%CI 90–100%) improved. Furthermore, surgery showed improvement in 96% (95%CI 78–100%) for both diplopia and ophthalmoplegia. The most common surgical complications were hypesthesia (19%; 95%CI 10–30%), ptosis and diplopia (both 17%; 95%CI, respectively, 10–26% and 5–33%) and ophthalmoplegia (16%; 95%CI 10–24). Conclusion Patients with spheno‐orbital meningioma usually present with proptosis or unilateral decreased visual acuity. Surgery shows to be effective in improving visual acuity and visual field deficits with mostly minor and well‐tolerated complications.

To report the first experience of our multidisciplinary team with functional imaging usingIn eighteen patients with prolactinoma, referred to our tertiary referral centre because of intolerance or resistance for dopamine agonists (DA), Met-PET/MRIMet-PET/MRIMet-PET/MRI

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) 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.

Background Whereas biochemical response is often used as a primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for patients to consider treatment successful. We performed a systematic review and meta-analysis to assess the effect of treatment on symptoms and HRQoL in acromegaly. Methods Seven electronic databases were searched for longitudinal studies assessing patient-reported symptoms or HRQoL in acromegaly. Meta-analyses were performed to assess differences during treatment for the Acromegaly Quality of Life Questionnaire (AcroQoL) and Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and standardized mean difference (SMD) for individual symptoms (interpretation: 0.2 small, 0.5 moderate, and 0.8 large effect). Treatment-naive and previously treated patients were assessed separately. Results Forty-six studies with 3301 patients were included; 24 contributed to quantitative analyses. Thirty-six studies used medication as main treatment, 1 transsphenoidal adenomectomy, and 9 various treatments. Symptoms and HRQoL both improved: AcroQoL increased 2.9 points (95% CI, 0.5 to 5.3 points), PASQ decreased –2.3 points (95% CI, –1.3 to –3.3 points), and individual symptom scores decreased for paresthesia –0.9 (95% CI, –0.6 to –1.2), hyperhidrosis –0.4 (95% CI, –0.1 to –0.6), fatigue –0.3 (95% CI, –0.1 to –0.6), arthralgia –0.3 (95% CI, –0.1 to –0.5), headache –0.3 (95% CI, 0.0 to –0.6), and soft-tissue swelling –0.2 (95% CI, 0.0 to –0.4). Conclusion Symptoms and HRQoL improved during acromegaly treatment. Consensus is needed on which symptoms should be included in a potential core outcome set, taking into account symptom frequency, severity, and sensitivity to change, which can be used in clinical practice and as outcome in trials.

Objective Full blood count (FBC) and serum inflammation-based scores reflect systemic inflammation and predict outcomes in cancer, but little is known in pituitary adenomas (PAs). We aimed to characterise FBC and inflammation-based scores in PA patients and investigate their usefulness in predicting challenging disease course. Methods We studied 424 PA patients first operated at our centre with available pre-operative biochemical data. Patients with infection, malignancies, autoimmune or haematological conditions were excluded. Inflammation-based scores studied: Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR), Systemic Immune-Inflammation Index (SII), Neutrophil-Platelet Score (NPS), Prognostic Nutrition Index (PNI), and Glasgow Prognostic Score (GPS). Results Cushing's disease patients had more platelets, leucocytes, neutrophils and monocytes, and higher NLR, NPS and SII. Serum inflammation-based scores didn't differ among non-Cushing PA subtypes. The glucocorticoid excess severity influenced leucocyte, eosinophil, basophil and platelet counts, and GPS in Cushing's disease. Patients with functioning non-Cushing PAs with suprasellar extension, cavernous sinus invasion and hypopituitarism had GPS >= 1, while NPS >= 1 was associated with suprasellar extension. More invasive and difficult to treat corticotrophinomas were associated with fewer platelets pre-operatively (< 299.5 x 10(9)/L predicting multimodal treatment). Non-functioning PA patients who suffered apoplexy had more leucocytes, neutrophils and monocytes, higher GPS >= 1 and fewer platelets; re-operated cases had fewer lymphocytes, higher NLR and PLR. Conclusions Serum inflammation-based scores may predict invasive/refractory PAs: GPS and PNI in non-functioning and functioning non-Cushing PAs; NPS in functioning non-Cushing PAs; NLR and PLR in non-functioning PAs. Platelets < 299.5 x 10(9)/L predict multimodal treatment in Cushing's disease. Further studies are needed to confirm these observations.

Context Joint complaints in patients with acromegaly are common, although the long-term disease course is largely unknown. Objective This study aims to evaluate the long-term course of acromegalic arthropathy. Design and Setting A prospective longitudinal cohort study was conducted in controlled acromegaly patients followed at a tertial referral center, with 3 study visits: at baseline and after a median of 2.6 and 9.1 years. Patients We included 31 patients with biochemically controlled acromegaly for 2 or more years (49% female; median age, 60 years) at baseline. Main Outcome Measures Radiographic arthropathy of the knee, hip, hand, and cervical and lumbar spine were evaluated using Kellgren and Lawrence (KL) scores, developed for assessment of primary osteoarthritis (OA). Radiographic progression was defined as a KL increase above the smallest detectable change. Joint symptoms were assessed using self-reported questionnaires. Progression was defined using existing clinically important cutoff values. Risk factors for progression were investigated using a multivariable model. Results All patients had definite radiographic OA at 1 or more joints at baseline. Radiographic progression was observed in 29%, 48%, 84%, and 94% of patients in the knees, hips, hands, and axial joints, respectively. Deterioration in hand-related pain and function was observed in 10 (32.3%) and 11 patients (35.5%), respectively. Solely baseline KL scores of the hip were associated with hip OA progression (OR 1.88; 95% CI, 1.09-3.16). Conclusions Acromegalic arthropathy showed significant radiographic progression over 9.1 years of follow-up in patients in remission, whereas clinical progression was observed less frequently. Future studies should focus on adequate prevention and treatment strategies of acromegalic arthropathy.

Introduction Meningioma is a heterogeneous disease and patients may suffer from long-term tumor- and treatment-related sequelae. To help identify patients at risk for these late effects, we first assessed variables associated with impaired long-term health-related quality of life (HRQoL) and impaired neurocognitive function on group level (i.e. determinants). Next, prediction models were developed to predict the risk for long-term neurocognitive or HRQoL impairment on individual patient-level. Methods Secondary data analysis of a cross-sectional multicenter study with intracranial WHO grade I/II meningioma patients, in which HRQoL (Short-Form 36) and neurocognitive functioning (standardized test battery) were assessed. Multivariable regression models were used to assess determinants for these outcomes corrected for confounders, and to build prediction models, evaluated with C-statistics. Results Data from 190 patients were analyzed (median 9 years after intervention). Main determinants for poor HRQoL or impaired neurocognitive function were patients’ sociodemographic characteristics, surgical complications, reoperation, radiotherapy, presence of edema, and a larger tumor diameter on last MRI. Prediction models with a moderate/good ability to discriminate between individual patients with and without impaired HRQoL (C-statistic 0.73, 95% CI 0.65 to 0.81) and neurocognitive function (C-statistic 0.78, 95%CI 0.70 to 0.85) were built. Not all predictors (e.g. tumor location) within these models were also determinants. Conclusions The identified determinants help clinicians to better understand long-term meningioma disease burden. Prediction models can help early identification of individual patients at risk for long-term neurocognitive or HRQoL impairment, facilitating tailored provision of information and allocation of scarce supportive care services to those most likely to benefit.

Abtract Background Most spheno-orbital meningioma series span multiple decades, and predictors of visual outcomes have not yet been systemically assessed. We describe visual outcomes in a recent cohort and assess predictors of postoperative visual outcomes. Methods Consecutive case series operated by a team of a neurosurgeon and orbital surgeon between May 2015 and January 2019. Best corrected visual acuity (BCVA), visual fields (static perimetry), and relative proptosis were measured preoperatively and postoperatively at 3/6/12 months after which it was assessed yearly. Predictors were assessed with linear regression analysis. Results Nineteen patients (all WHO grade I) were operated by the pterional approach (median follow-up 2.4 years). Preoperative visual acuity deficits (n = 10) normalized in 70% and improved in 10% (median preoperative: 0.8, postoperative: 1.2, p = 0.021). Preoperative visual field deficits (n = 8) normalized in all patients (preoperative: − 6.5 dB, postoperative: − 1.5 dB, p = 0.008). Preoperative proptosis (n = 16) normalized in 44% and improved in 56% (preoperative: 5 mm, postoperative: 2 mm, p 12 months) BCVA were worse preoperative BCVA (p = 0.002) and diagnosis of multiple meningioma (p = 0.021). Predictors for worse longer-term visual fields were higher diameter of hyperostosis (p = 0.009) and higher Simpson grade (p = 0.032). Predictor for short-term (3 months) proptosis was preoperative proptosis (p = 0.006). Conclusion We recommend surgery, even of patients with minimal visual impairment or hyperostosis, as patients who present with deteriorated visual function or extensive hyperostosis are less likely to have postoperative visual outcomes restored to normal.

Purpose Pituitary diseases severely affect patients’ health-related quality of life (HRQoL). The most frequently used generic HRQoL questionnaire is the Short Form-36 (SF-36). The shorter 12-item version (SF-12) can improve efficiency of patient monitoring. This study aimed to determine whether SF-12 can replace SF-36 in pituitary care. Methods In a longitudinal cohort study (August 2016 to December 2018) among 103 endoscopically operated adult pituitary tumor patients, physical and mental component scores (PCS and MCS) of SF-36 and SF-12 were measured preoperatively, and 6 weeks and 6 months postoperatively. Chronic care was assessed with a cross-sectional study (N = 431). Mean differences and agreement between SF-36 and SF-12 change in scores (preoperative vs. 6 months) were assessed with intraclass correlation coefficients (ICC) and limits of agreement, depicting 95% of individual patients. Results In the longitudinal study, mean differences between change in SF-36 and SF-12 scores were 1.4 (PCS) and 0.4 (MCS) with fair agreement for PCS (ICC = 0.546) and substantial agreement for MCS (ICC = 0.931). For 95% of individual patients, the difference between change in SF-36 and SF-12 scores varied between −14.0 and 16.9 for PCS and between −7.8 and 8.7 for MCS. Cross-sectional results showed fair agreement for PCS (ICC = 0.597) and substantial agreement for MCS (ICC = 0.943). Conclusions On a group level, SF-12 can reliably reproduce MCS in pituitary patients, although PCS is less well correlated. However, individual differences between SF-36 and SF-12 can be large. For pituitary diseases, alternative strategies are needed for concise, but comprehensive patient-reported outcome measurement.

ObjectivesTo 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.DesignQualitative study using semistructured interviews based on the attitudes, social influence and self-efficacy model and expert knowledge.ParticipantsTwelve patients who underwent transsphenoidal pituitary gland tumour surgery and received an IDUC during or after surgery.SettingOne patient was interviewed in the endocrinology outpatient clinic and 11 patients were interviewed on the neurosurgery ward.ResultsFive 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.ConclusionsThis 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.

Clinically non-functioning pituitary adenomas (NFPAs) usually present with mass effects. Transsphenoidal surgery is the cornerstone of treatment once there is an indication for decompression. In smaller NFPAs, a wait-and-scan policy is usually considered. After surgery tumour remnants are closely followed with MRI and ophthalmological evaluation. Adjuvant radiotherapy can be performed in case there is a remnant, however, given the slow growth tendency a wait and scan policy and postponing radiotherapy is an alternative approach, especially in patients with normal pituitary function. Recent years there are some innovations with respect to medical treatment. Cabergoline may help with tumour stabilization in a subset of patients and temozolomide can be attempted in aggressive forms of pituitary adenoma.

Context The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. Objective To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. Methods Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. Results A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. Conclusions In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.

ContextThe increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo–pituitary–end organ hormone axes, remains unclear.ObjectiveThe aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function.MethodsEight electronic databases were searched for articles published up to May 8, 2018. Fixed or random effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals (CI). This study is reported following the PRISMA and MOOSE guidelines.Data synthesis52 studies (22 low risk of bias) were included describing 18 428 subjects, consisting of patients with chronic pain (n = 21 studies) or on maintenance treatment for opioid addiction (n = 9) and healthy volunteers (n = 4). The most frequently used opioid was methadone (n = 13 studies), followed by morphine (n = 12). Prevalence of hypogonadism was 63% (95% CI: 55%–70%, 15 studies, 3250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and nondynamic testing was 15% (95% CI: 6%–28%, 5 studies, 205 patients, 57.5% males) and including only studies using the insulin tolerance tests 24% (95% CI 16%–33%, 2 studies, n = 97 patients). In 5 out of 7 studies, hyperprolactinemia was present. No clear effects on the somatotropic and hypothalamo–pituitary–thyroid axes were described.ConclusionsHypogonadism occurs in more than half of male opioid users, and hypocortisolism in approximately one-fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable.

PurposeNon-functioning pituitary adenomas (NFPA) have a substantial impact on patients’ healthstatus, yet research on the extent of healthcare utilization and costs among these patients isscarce. The objective was to determine healthcare usage, associated costs, and theirdeterminants among patients treated for an NFPA.MethodsIn a cross-sectional study, 167 patients treated for an NFPA completed four validatedquestionnaires. Annual healthcare utilization and associated costs were assessed through themedical consumption questionnaire (MTA iMCQ). In addition, the Leiden Bother and NeedsQuestionnaire for pituitary patients (LBNQ-Pituitary), Short Form-36 (SF-36), and EuroQol(EQ-5D) were administered. Furthermore, age, sex, endocrine status, treatment, and durationof follow-up were extracted from the medical records. Associations were analyzed usinglogistic/linear regression.ResultsAnnual healthcare utilization included: consultation of an endocrinologist (95% of patients),neurosurgeon (14%), and/or ophthalmologist (58%). Fourteen percent of patients had ≥1hospitalization(s) and 11% ≥1 emergency room visit(s). Mean overall annual healthcare costswere € 3040 (SD 6498), highest expenditures included medication (31%), inpatient care(28%), and specialist care (17%). Factors associated with higher healthcare utilization andcosts were greater self-perceived disease bother and need for support, worse mental andphysical health status, younger age, and living alone.ConclusionHealthcare usage and costs among patients treated for an NFPA are substantial and were associated with self-perceived health status, disease bother, and healthcare needs rather thanendocrine status, treatment, or duration of follow-up. These findings suggest that targetedinterventions addressing disease bother and unmet needs in the chronic phase are needed.

Context Insight into the current landscape of patient-reported outcome (PRO) measures (PROM) and differences between PROs and conventional biochemical outcomes is pivotal for future implementation of PROs in research and clinical practice. Therefore, in studies among patients with acromegaly and growth hormone deficiency (GHD), we evaluated (1) used PROMs, (2) their validity, (3) quality of PRO reporting, (4) agreement between PROs and biochemical outcomes, and (5) determinants of discrepancies. Evidence Acquisition We searched 8 electronic databases for prospective studies describing both PROs and biochemical outcomes in acromegaly and GHD patients. Quality of PRO reporting was assessed using the International Society for Quality of Life Research (ISOQOL) criteria. Logistic regression analysis was used to evaluate determinants. Evidence Synthesis Ninety studies were included (acromegaly: n = 53; GHD: n = 37). Besides nonvalidated symptom lists (used in 37% of studies), 36 formal PROMs were used [predominantly Acromegaly Quality of Life Questionnaire in acromegaly (43%) and Quality of Life-Assessment of Growth Hormone Deficiency in Adults in GHD (43%)]. Reporting of PROs was poor, with a median of 37% to 47% of ISOQOL items being reported per study. Eighteen (34%) acromegaly studies and 12 (32%) GHD studies reported discrepancies between PROs and biochemical outcomes, most often improvement in biochemical outcomes without change in PROs. Conclusions Prospective studies among patients with acromegaly and GHD use a multitude of PROMs, often poorly reported. Since a substantial proportion of studies report discrepancies between PROs and biochemical outcomes, PROMs are pivotal in the evaluation of disease activity. Therefore, harmonization of PROs in clinical practice and research by development of core outcome sets is an important unmet need.

Purpose 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.

Background Little is known about long-term caregiver burden in meningioma patients. We assessed meningioma caregiver burden, its association with informal caregiver’s well-being and possible determinants. Methods In this multicenter cross-sectional study, informal caregivers completed the Caregiver Burden Scale (five domains and total score). Patients completed a disease-specific health-related quality of life (HRQoL) questionnaire focusing on symptoms (EORTC QLQ-BN20) and underwent neurocognitive assessment. Both groups completed a generic HRQoL questionnaire (SF-36) and the Hospital Anxiety, and Depression Scale. We assessed the association between caregiver burden and their HRQoL, anxiety and depression. Furthermore, we assessed determinants for the caregiver burden. Multivariable regression analysis was used to correct for confounders. Results One hundred and twenty-nine informal caregivers were included (median 10 years after patients’ treatment). Caregivers reported burden in ≥1 domain (34%) or total burden score (15%). A one-point increase in total caregiver burden score was associated with a clinically relevant decrease in caregiver’s HRQoL (SF-36) in 5/8 domains (score range: −10.4 to −14.7) and 2/2 component scores (−3.5 to −5.9), and with more anxiety (3.8) and depression (3.0). Patients’ lower HRQoL, increased symptom burden, and increased anxiety and depression were determinants for higher caregiver burden, but not patients’ or caregivers’ sociodemographic characteristics, patients’ neurocognitive functioning, or tumor- and treatment-related characteristics. Conclusions Ten years after initial treatment, up to 35% of informal caregivers reported a clinically relevant burden, which was linked with worse HRQoL, and more anxiety and depression in both patients and caregivers, emphasizing the strong interdependent relationship. Support for meningioma caregivers is therefore warranted.

BACKGROUND Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention. OBJECTIVE To assess the long-term (≥5 yr) disease burden of meningioma patients. METHODS In this multicenter cross-sectional study, patients ≥5 yr after intervention (including active magnetic resonance imaging (MRI) surveillance) were included and assessed for HRQoL (Short-Form Health Survey 36), neurocognitive functioning (neuropsychological assessment), anxiety and depression (Hospital Anxiety and Depression Scale), and work productivity (Short Form-Health and Labour Questionnaire). Multivariable and propensity score regression analyses were used to compare patients and controls, and different treatment strategies corrected for possible confounders. Clinically relevant differences were reported. RESULTS At a median of 9 yr follow-up after intervention, meningioma patients (n = 190) reported more limitations due to physical (difference 12.5 points, P = .008) and emotional (13.3 points, P = .002) health problems compared with controls. Patients also had an increased risk to suffer from anxiety (odds ratio [OR]: 2.6, 95% CI: 1.2-5.7) and depression (OR: 3.7, 95% CI: 1.3-10.5). Neurocognitive deficits were found in 43% of patients. Although postoperative complications, radiotherapy, and reresection were associated with worse verbal memory, attention, and executive functioning when compared to patients resected once, the only clinically relevant association was between reresection and worse attention (–2.11, 95% CI: –3.52 to –0.07). Patients of working age less often had a paid job (48%) compared with the working-age Dutch population (72%) and reported more obstacles at work compared with controls. CONCLUSION In the long term, a large proportion of meningioma patients have impaired HRQoL, neurocognitive deficits, and high levels of anxiety or depression. Patients treated with 1 resection have the best neurocognitive functioning., Graphical Abstract Graphical Abstract

Objective The extended endoscopic approach provides unimpaired visualization and direct access to ventral skull base pathology, but is associated with cerebrospinal fluid (CSF) leak in up to 25% of patients. To evaluate the impact of improved surgical techniques and devices to better repair skull base defects, we assessed published surgical outcomes of the extended endoscopic endonasal approach in the last two decades for a well-defined homogenous group of tuberculum sellae and olfactory groove meningioma patients. Methods Random-effects meta-analyses were performed for studies published between 2004 (first publications) and April 2020. We evaluated CSF leak as primary outcome. Secondary outcomes were gross total resection, improvement in visual outcomes in those presenting with a deficit, intraoperative arterial injury, and 30-day mortality. For the main analyses, publications were pragmatically grouped based on publication year in three categories: 2004–2010, 2011–2015, and 2016–2020. Results We included 29 studies describing 540 patients with tuberculum sellae and 115 with olfactory groove meningioma. The percentage patients with CSF leak dropped over time from 22% (95% CI: 6–43%) in studies published between 2004 and 2010, to 16% (95% CI: 11–23%) between 2011 and 2015, and 4% (95% CI: 1–9%) between 2016 and 2020. Outcomes of gross total resection, visual improvement, intraoperative arterial injury, and 30-day mortality remained stable over time Conclusions We report a noticeable decrease in CSF leak over time, which might be attributed to the development and improvement of new closure techniques (e.g., Hadad-Bassagasteguy flap, and gasket seal), refined multilayer repair protocols, and lumbar drain usage.

Full blood count (FBC) and serum inflammation-based scores reflect systemic inflammation and predict outcomes in cancer, but little is known in pituitary adenomas (PAs). We aimed to characterise FBC and inflammation-based scores in PA patients and investigate their usefulness in predicting challenging disease course.We studied 424 PA patients first operated at our centre with available pre-operative biochemical data. Patients with infection, malignancies, autoimmune or haematological conditions were excluded. Inflammation-based scores studied: Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR), Systemic Immune-Inflammation Index (SII), Neutrophil-Platelet Score (NPS), Prognostic Nutrition Index (PNI), and Glasgow Prognostic Score (GPS).Cushing's disease patients had more platelets, leucocytes, neutrophils and monocytes, and higher NLR, NPS and SII. Serum inflammation-based scores didn't differ among non-Cushing PA subtypes. The glucocorticoid excess severity influenced leucocyte, eosinophil, basophil and platelet counts, and GPS in Cushing's disease. Patients with functioning non-Cushing PAs with suprasellar extension, cavernous sinus invasion and hypopituitarism had GPS ≥ 1, while NPS ≥ 1 was associated with suprasellar extension. More invasive and difficult to treat corticotrophinomas were associated with fewer platelets pre-operatively ( 299.5 × 10Serum inflammation-based scores may predict invasive/refractory PAs: GPS and PNI in non-functioning and functioning non-Cushing PAs; NPS in functioning non-Cushing PAs; NLR and PLR in non-functioning PAs. Platelets 299.5 × 10

Background The association between spontaneous cerebrospinal fluid (CSF) leak/rhinorrhea and idiopathic intracranial hypertension (IIH) has been increasingly recognized over the last years. However, considerable variability of opinion regarding the assessment, investigations, and management of patients with spontaneous CSF rhinorrhea remains. Methods A consensus group was formed from experts from Europe, Asia, Australia, South and North America. Following literature review and open discussions with members of the panel, a set of 61 statements was produced. A modified Delphi method was used to refine expert opinion with 3 rounds of questionnaires and a consensus group meeting in Santo-Rhino meeting in September 2019. Results Fifty statements (82% of total) on spontaneous CSF leak and IIH reached consensus. In 38 of 50 statements, the median response was 7 (strongly agree) and in the 12 remaining statements the median response was 6 (agree). Eleven statements were excluded because they did not reach consensus and one new statement was added during SantoRhino meeting. The final statements refer to patient history and clinical examination ("History taking should include presence of headache, tinnitus and visual defects"), investigations (role of Thin Slice Computed Tomography and CISS/FLAIR sequences in Magnetic Resonance Imaging), principles of management (watchful waiting or measures to reduce ICP are supplementary but cannot subsitute surgical closure), surgical technique, intraoperative, early postoperative and long term management. Conclusion We present fifty consensus statements on the diagnosis, investigation, and management of spontaneous CSF rhinorrhea based on the currently available evidence and expert opinion. Although by no means comprehensive and final, we believe they can contribute to the standardization of clinical practice. Early diagnosis, prompt surgical closure of the defect, assesment for and treatment of potentially co-existing idiopathic intracranial hypertension in a comprehensive multidisciplinary approach are essential in order to successfully manage spontaneous CSF rhinorrhea, reduce associated morbidity and prevent recurrence.

Purpose To evaluate whether the occurrence of chiasmal herniation coincides with visual field (VF) deterioration and to compare the course of VF defects in patients with and without radiological chiasmal herniation following treatment of pituitary adenoma. Methods This retrospective cohort study included 48 pituitary macroadenoma patients with chiasm compression, divided into three groups: Group 1 (N = 12), downward displaced optic chiasm and deteriorated VFs; Group 2 (N = 16), downward displaced optic chiasm; Group 3 (N = 20), control-group matched for tumour size and follow-up VFs, in mean deviation (dB). VFs were compared over time and a severity index, Chiasm Herniation Scale (CHS), for herniation based on radiological parameters was designed. Results After treatment, all groups showed improvement of VFs (Gr1: 2.97 dB p = 0.097, Gr2: 4.52 dB p = 0.001 and Gr3: 5.16 dB p = 0.000), followed by long-term gradual deterioration. The course of VFs between patients with and without herniation was not significantly different (p = 0.143), neither was there a difference in the course before and after herniation (p = 0.297). The median time till onset of herniation was 40 months (IQR 6 month-10 years) and did not significantly differ (p = 0.172) between the groups. There was no relation between VFs and the degree of herniation (p = 0.729). Conclusion Herniation does not appear to have clinical relevance with respect to VF outcome. The newly designed CHS is the first scoring system to quantify the severity of herniation and, in the absence of alternatives, may be useful to describe MRI findings to serve future added value in larger sized outcome studies.

Purpose Prolactinomas are the most prevalent functioning pituitary adenomas. They affect gonadal function as well as health-related quality of life (HRQoL). This study aimed to report healthcare utilization and costs, including their determinants, for prolactinoma patients. Methods Cross-sectional study of 116 adult prolactinoma patients in chronic care in a Dutch tertiary referral center. Patients completed four validated questionnaires, assessing healthcare utilization and costs over the previous 12 months (Medical Consumption Questionnaire), disease bother and needs (Leiden Bother and Needs Questionnaire Pituitary), HRQoL (Short Form-36), and self-reported health status (EuroQol 5D). Regression analyses were used to assess associations between disease-related characteristics and healthcare utilization and costs. Results Mean age was 52.0 years (SD 13.7) and median follow-up was 15.0 years (IQR 7.6–26.1). Patients visited the endocrinologist (86.2%), general practitioner (37.9%), and ophthalmologist (25.0%) most frequently. Psychological care was used by 12.9% of patients and 5% were admitted to hospital. Mean annual healthcare costs were €1928 (SD 3319), mainly for pituitary-specific medication (37.6% of total costs), hospitalization (19.4%) and specialist care (16.1%). Determinants for higher healthcare utilization and costs were greater disease bother and needs for support, lower HRQoL, elevated prolactin, and longer disease duration, while tumor size, hypopituitarism and adrenal insufficiency were not significantly associated with healthcare utilization and costs. Conclusion Healthcare utilization and costs of prolactinoma patients are related to patient-reported HRQoL, bother by disease and needs for support. Therefore, addressing patients’ HRQoL and needs is a way forward to improve efficiency of care and patients’ health status.

Purpose Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt symptoms of DI, but can also reflect several physiological adaptive mechanisms in the postoperative phase. These may be difficult to distinguish from and might coincide with DI. The difficulty to distinguish DI from other causes of postoperative polyuria might explain the high variation in incidence rates. This limits interpretation of outcomes, in particular complication rates between centers, and may lead to unnecessary treatment. Aim of this review is to determine a pathophysiologically sound and practical definition of DI for uniform outcome evaluations and treatment recommendations. Methods This study incorporates actual data and the experience of our center and combines this with a review of literature on pathophysiological mechanisms and definitions used in clinical studies reporting of postoperative DI. Results The occurrence of excessive thirst and/or hyperosmolality or hypernatremia are the best indicators to discriminate between pathophysiological symptoms and signs of DI and other causes. Urine osmolality distinguishes DI from osmotic diuresis. Conclusions To improve reliability and comparability we propose the following definition for postoperative DI: polyuria (urine production > 300 ml/hour for 3 h) accompanied by a urine specific gravity (USG) 300 mosmol/kg, or serum sodium > 145 mmol/L. To prevent unnecessary treatment with desmopressin, we present an algorithm for the diagnosis and treatment of postoperative DI.

Endoscopic transsphenoidal surgery for pituitary adenomas is a safe and highly effective first-line treatment that is well tolerated by patients. There are many potential complications, and there is a large variation in complexity of surgery. This article presents the philosophy, surgical techniques, and outcomes of a high-volume pituitary adenoma center. Three surgical videos illustrate some procedures. The experience has reinforced the authors' belief that experience and surgical volume are key to high quality of care.

Purpose Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related to the preoperative severity of dysfunction is unknown. Methods Systematic review for evidence to provide clinical guidance for timing of surgical decompression of the optic chiasm, and a cohort study of 30 NFMA patients, in whom mean deviation (MD), and severity of visual dysfunction was assessed. Results Systematic review 44 studies were included with a total of 4789 patients. Postoperatively, visual field defects improved in 87.0% of patients, stabilized in 12.8% and worsened in 1.0%. Specific protocols regarding timing of surgery were not reported. Only seven studies (16.7%) reported on either the duration of visual symptoms, or diagnostic, or treatment delay. Cohort study 30 NFMA patients (50% female, 60 eyes, mean age 58.5 ± 14.8 years), had a median MD of − 5.3 decibel (IQR − 3.1 to − 10.1). MD was strongly correlated with clinical severity (r = − 0.94, P − 2 dB, (2) mild − 2 dB to − 4 dB, (3) moderate − 4 to − 8 dB, (4) severe − 8 to − 17 dB, (5) very severe Conclusion Surgical decompression is highly effective in improving visual function. Uniform, quantitative grading of visual dysfunction was lacking. MD is a promising quantitative outcome measure. We provide recommendations for the evaluation of timing of surgery, considering severity of visual impairment, which will need further validation based on expert clinical practice.

Objective Discharge policies concerning hospitalization after endoscopic pituitary tumor surgery are highly variable. A few studies support fast-track discharge; however, this is not commonplace. Our goal was to report the transition to and evaluate the feasibility, safety, clinical- and patient-reported outcomes and costs of fast-track care in pituitary surgery. Methods This observational study included 155 patients undergoing pituitary surgery between December 2016 and December 2018. Fast-track care consisted of planned discharge 2–3 days after surgery, followed by daily surveillance by a case manager. All outcomes were compared with patients not eligible for fast-track discharge. The total group (fast-track and non-fast-track) was compared with historic controls (N = 307). Results A total of 79/155 patients (51%) were considered eligible for fast-track discharge, of whom 69 (87%) were discharged within 3 days. The total group was discharged more often within 3 days compared with historic controls (49 vs. 20%, p p = 0.363). Although the total group had more readmissions compared with historic controls (17 vs. 10%, p = 0.002), no life-threatening complications occurred after discharge. On average, clinical- and patient-reported outcomes improved over time, both in the fast-track and non-fast-track groups. The mean overall costs within 30 days after surgery did not differ between the total group € 9992 (SD € 4562) and historic controls € 9818 (SD € 3488) (p = 0.649). Conclusion A stratified fast-track care trajectory with enhanced postoperative outpatient surveillance after pituitary tumor surgery is safe and feasible. As expected, costs of the fast-track were lower than the non-fast-track group, however we could not prove overall cost-effectiveness compared with the historic controls.

Background It has been suggested that lack of ongoing registration of patient-centered outcomes has resulted in existing care trajectories that have not been optimized for sequelae experienced by meningioma patients. This study aimed to evaluate the structure of current meningioma care and identify issues and potential high-impact improvement initiatives. Methods Using the grounded theory approach, a thematic framework was constructed based on the Dutch Comprehensive Cancer Organisation survey about issues in meningioma care trajectories. This framework was used during 3 semistructured interviews and 2 focus groups with patient-partner dyads (n = 16 participants), and 2 focus groups with health care providers (n = 11 participants) to assess issues in current meningioma care trajectories and possible solutions, including barriers to and facilitators for implementation. Results Identified issues (n = 18 issues) were categorized into 3 themes: availability and provision of information, care and support, and screening for (neurocognitive) rehabilitation. A lack of information about the intervention and possible outcomes or complications, lack of support after treatment focusing on bodily and psychological functions, and reintegration into society were considered most important. Sixteen solutions were suggested, such as appointment of case managers (solution for 11/18 issues, 61%), assessment and treatment by physiatrists (22%), and routine use of patient-reported outcome measures for patient monitoring (17%). Barriers for these solutions were lack of budget, capacity, technology infrastructure, and qualified personnel with knowledge about issues experienced by meningioma patients. Conclusions This study identified issues in current multidisciplinary meningioma care that are considered unmet needs by patients, partners, and health care providers and could guide innovation of care.

Purpose To assess the reliability and safety of a postsurgical evaluation strategy of adrenal function using CRH stimulation and basal cortisol concentrations after transsphenoidal pituitary surgery. Methods Retrospective cohort study of all patients undergoing endoscopic transsphenoidal surgery from 2010 to 2017, in whom early postoperative basal cortisol and/or CRH-stimulated cortisol secretion were available, including confirmation of adrenal function during follow-up. Patients with Cushing’s disease were excluded. Optimal test performances were assessed using ROC analysis. Results A total of 156 patients were included. Sensitivity and specificity of the CRH test were 78% and 90%, respectively, and 86% and 92% for basal cortisol, respectively, using an optimal cutoff of 220 nmol/L. Eight patients had false-negative test results with the CRH test (normal test but adrenal insufficient at follow-up), and six patients with basal cortisol, the majority of which had multiple pituitary hormone deficiencies and fluid imbalances. No clinical adverse events occurred in patients with false-negative test results. The diagnostic performance of a single basal cortisol measurement was superior to the CRH test. Conclusions The early postoperative basal cortisol is a safe and simple measurement to guide (dis)continuation of hydrocortisone replacement. However, disturbing factors, e.g., sodium balance disorders, contraceptives, untreated hypopituitarism, and illness impact the interpretation and in those cases this measure is unreliable. We propose an algorithm in which hydrocortisone replacement at discharge is based on basal cortisol

Systematic review and meta-analysis comparing endoscopic and microscopic transsphenoidal surgery for Cushing’s disease regarding surgical outcomes (remission, recurrence, and mortality) and complication rates. To stratify the results by tumor size. Nine electronic databases were searched in February 2017 to identify potentially relevant articles. Cohort studies assessing surgical outcomes or complication rates after endoscopic or microscopic transsphenoidal surgery for Cushing’s disease were eligible. Pooled proportions were reported including 95% confidence intervals. We included 97 articles with 6695 patients in total (5711 microscopically and 984 endoscopically operated). Overall, remission was achieved in 5177 patients (80%), with no clear difference between both techniques. Recurrence was around 10% and short term mortality

We present a 13-year-old boy who was admitted with complaints of a state of progressive sleepiness and a sudden headache with vomiting and fever. Laboratory testing showed hypoglycemia, multiple pituitary hormonal deficiencies, and an elevated C-reactive protein level. A cranial magnetic resonance imaging (MRI) showed an opaque sphenoid sinus and an intrasellar mass suggesting hemorrhage, so that we suspected pituitary apoplexy (PA) originating from a non-functioning adenoma, although a pituitary abscess could not completely be excluded. The boy was treated with antibiotics, hydrocortisone, and levothyroxine. Due to his rapid clinical improvement, no surgery was performed and we considered the diagnosis of PA as confirmed. At follow-up, the MRI scan showed a small residual lesion. Pituitary deficiencies of growth hormone, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, and vasopressin persisted. A literature search of all well-documented cases of PA in children or adolescents (n=30, 13 boys and 17 girls) indicated that this condition is rare below 20 years of age but must be considered when a patient experiences headache with or without visual disturbances, even in the presence of clinical and laboratory signals suggestive of pituitary abscess. MRI neuroimaging is helpful in the differential diagnosis. In both conditions, the possibility of ACTH deficiency should always be considered, investigated, and treated. In cases without severe neuro-ophthalmological deficits and/or with a rapid and positive response to acute medical management, one can abstain from surgical treatment.

Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related to the preoperative severity of dysfunction is unknown.Systematic review for evidence to provide clinical guidance for timing of surgical decompression of the optic chiasm, and a cohort study of 30 NFMA patients, in whom mean deviation (MD), and severity of visual dysfunction was assessed.Systematic review 44 studies were included with a total of 4789 patients. Postoperatively, visual field defects improved in 87.0% of patients, stabilized in 12.8% and worsened in 1.0%. Specific protocols regarding timing of surgery were not reported. Only seven studies (16.7%) reported on either the duration of visual symptoms, or diagnostic, or treatment delay. Cohort study 30 NFMA patients (50% female, 60 eyes, mean age 58.5 ± 14.8 years), had a median MD of - 5.3 decibel (IQR - 3.1 to - 10.1). MD was strongly correlated with clinical severity (r = - 0.94, P 0.0001), and were used for severity of defects cut-off values: (1) normal - 2 dB, (2) mild - 2 dB to - 4 dB, (3) moderate - 4 to - 8 dB, (4) severe - 8 to - 17 dB, (5) very severe - 17 dB.Surgical decompression is highly effective in improving visual function. Uniform, quantitative grading of visual dysfunction was lacking. MD is a promising quantitative outcome measure. We provide recommendations for the evaluation of timing of surgery, considering severity of visual impairment, which will need further validation based on expert clinical practice.

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.

OBJECTIVE The increased use of opioids has resulted in an unprecedented opioid epidemic, with non-negligible numbers of opioid-induced deaths. It is well-known that chronic opioid use affects the activity of the gonadal axis, but the frequency of this and other potential pituitary hormone deficiencies remains unclear. The aim of this systematic review and meta-analysis was to systematically review the effect of exogenous opioids on endocrine function METHODS Following the PRISMA statement, eight electronic databases were searched in May 2018 for randomized, and observational studies assessing endocrine function in patients using exogenous opioids. A random effects model meta-analysis was performed to obtain weighted proportions of hypogonadism and hypocortisolism with a 95% confidence interval. Due to the heterogeneity in studies, meta-analysis for the effects on other axes, and for subgroups could not be performed, and is systematically reviewed. RESULTS 52 articles were included with 18.428 patients in total. The patient population consisted mainly of pain patients (n=21 studies), patients on maintenance treatment for opioid addiction (n=9) and healthy volunteers (n=4) with similar opioid effects between these groups. Morphine (n=17) was mostly used, followed by methadone (n=15) and opioid dose defined as morphine equivalent daily dose (MEDD) (n=14) with no difference in effects between groups. Based on 15 studies containing 3.250 patients (% male: 99.5) on chronic opioids, the prevalence of hypogonadism was 65% (95% CI: 57% to 73%, I2=91.16%). Based on 5 studies with a total of 207 patients (% male: 57.5), the prevalence of hypocortisolism, based on non-dynamic testing, was 19% (95% CI: 10%, 29%, I2=74.21). Results of the systematic review showed an increasing trend for serum prolactin concentrations, and no clear effects on the somatotropic (n=5) and thyrotropic axes (n=7). Six studies reported that testosterone replacement in opioid induced hypogonadism increased testosterone levels, but clinical effects were not reported. CONCLUSION While the evidence on other endocrine axes remains insufficient, hypogonadism occurs in more than half of the male chronic opioid users, and hypocortisolism in approximately a fifth of all patients. Periodical evaluation of endocrine function, especially of the activity of the gonadal and adrenal axes, is mandatory in these patients. More studies are needed on the effects of chronic opioid use on the female gonadal axis and the other endocrine axes, also focusing on experienced symptoms and symptom management.

Background: First-choice treatment for Cushing's disease is transsphenoidal adenomectomy. Since its introduction in the 1970s, many centers have now switched from microscopic to endoscopic surgery. We compared both techniques for the treatment of Cushing's disease at the Leiden University Medical Center, a European reference center for pituitary diseases.Methods: Cohort study with inclusion and follow-up of consecutive Cushing's disease patients primarily treated by transsphenoidal surgery at the Leiden University Medical Center between 1978 and 2016. We compared remission rates (primary endpoint), mortality, and complications between microscopic (performed up to 2005) and endoscopic (performed from 2003 onwards) surgery. Subgroup analyses were performed by tumor size, surgical experience, and preoperative imaging techniques. Additionally, surgeons' intraoperative findings regarding presence and removal of the adenoma were related to surgical outcome.Results: Of 137 included patients, 87 were treated microscopically and 50 endoscopically. Three months after microscopic surgery, 74 patients (86%) were in remission. Five-year recurrence-free survival was 89% (95% confidence interval [CI]: 82-96%), and ten-year recurrence free survival was 84% (95% CI: 75-93%). After endoscopic surgery, 39 patients (83%) were in remission. Both five-year and ten-year recurrence-free survival were 71% (95% CI: 55-87%). Hazard ratio for recurrence was 0.47 (95% CI: 0.19-1.14), and for mortality 2.79 (95% CI: 0.35-22.51), for microscopic versus endoscopic surgery. No learning curve was found for endoscopy, nor an influence of preoperative imaging technique for microscopy. In addition, we did not find a clear relation between the surgeons' intraoperative findings and surgical outcomes.Conclusions: This study did not identify a clear advantage of microscopic or endoscopic transsphenoidal surgery for the treatment of Cushing's disease based on clinical outcome. The transition to endoscopic surgery at our center was not accompanied by transient worsening of outcomes, which may be reassuring for those considering transitioning.

Background The intraoperative distinction between normal and abnormal pituitary tissue is crucial during pituitary adenoma surgery to obtain a complete tumor resection while preserving endocrine function. Near-infrared (NIR) fluorescence imaging is a technique to intraoperatively visualize tumors by using indocyanine green (ICG), a contrast agent allowing visualization of differences in tissue vascularization. Although NIR fluorescence imaging has been described in pituitary surgery, it has, in contrast to other surgical areas, never become widely used. Objective To evaluate NIR fluorescence imaging in pituitary surgery, both qualitatively and quantitatively, and to assess the additional value of resecting adenoma tissue under NIR fluorescence guidance. Methods We included 10 patients planned to undergo transnasal transsphenoidal selective adenomectomy. Patients received multiple intravenous administrations of 5 mg ICG, up to a maximum of 15 mg per patient. Endoscopic NIR fluorescence imaging was performed at multiple points in time. The NIR fluorescent signal in both the adenoma and pituitary gland was obtained, and the fluorescence contrast ratio was assessed. Results Four patients had Cushing disease, 1 had acromegaly, and 1 had a prolactinoma. Four patients had a nonfunctioning macroadenoma. In 9 of 10 patients with a histologically proven pituitary adenoma, the normal pituitary gland showed a stronger fluorescent signal than the adenoma. A fluorescence contrast ratio of normal pituitary gland to adenoma of 1.5 ± 0.2 was obtained. In 2 patients; adenoma resection was actually performed under NIR fluorescence guidance instead of under white light. Conclusion NIR fluorescence imaging can easily and safely be implemented in pituitary surgery. The timing of ICG administration is important for optimal results and warrants further study. It appears that injection of ICG can best be postponed until some part of the normal pituitary gland is identified. Subsequent repeated low-dose ICG administrations improved the distinction between adenoma and gland.

Introduction Pituitary tumors may have a considerable impact on patients’ functional status, including paid employment, yet research in this area is sparse. Objective To describe work disability and its determinants in patients treated for a pituitary tumor. Methods Cross-sectional study including patients treated for a pituitary tumor in the working age (18–65 years), who completed five validated questionnaires assessing work disability [Short Form-Health and Labour Questionnaire, Work Role Functioning Questionnaire 2.0 (WRFQ)], health-related quality of life (HRQoL) and utility (Short Form-36, EuroQoL) and disease burden (Leiden Bother and Needs Questionnaire-Pituitary). Additional data were extracted from the medical records (age, gender, tumor type, treatment, date of diagnosis) and self-reports (marital status, education, endocrine status). Associations of disease-specific and sociodemographic characteristics, HRQoL, and disease burden with (not) having a paid job were examined through multivariate logistic regression. Results We included 241 patients (61% female, median age 53 years, median time since diagnosis 11 years), of whom 68 (28%) were without a paid job. Patients who had acromegaly, Cushing’s disease, (pan)hypopituitarism, radiotherapy, were single, less educated, lower HRQoL, and increased disease burden were more often without a paid job (p