Publications by authors named "Nienke R Biermasz"

173 Publications

The PRolaCT studies - a study protocol for a combined randomised clinical trial and observational cohort study design in prolactinoma.

Trials 2021 Sep 25;22(1):653. Epub 2021 Sep 25.

Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands.

Background: 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-naïve 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.

Trial Registration: US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480 . Registered on 27 September 2019, registered retrospectively (by 2 months).
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http://dx.doi.org/10.1186/s13063-021-05604-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465768PMC
September 2021

Low sclerostin levels after long-term remission of acromegaly.

Endocrine 2021 Aug 26. Epub 2021 Aug 26.

Department of Medicine, Division of Endocrinology, and Center for Endocrine Tumors Leiden, Leiden, The Netherlands.

Purpose: Bone health is compromised in acromegaly resulting in vertebral fractures (VFs), regardless of biochemical remission. Sclerostin is a negative inhibitor of bone formation and is associated with increased fracture risk in the general population. Therefore, we compared sclerostin concentrations between well-controlled acromegaly patients and healthy controls, and assessed its relationship with bone mineral density (BMD), and VFs in acromegaly.

Methods: Seventy-nine patients (mean age 58.9 ± 11.4 years, 49% women) with controlled acromegaly, and 91 healthy controls (mean age 51.1 ± 16.9 years, 59% women) were included. Plasma sclerostin levels (pg/mL) in patients were measured with an ELISA assay, whereas in controls, serum levels were converted to plasma levels by multiplication with 3.6. In patients, VFs were radiographically assessed, and BMD was assessed using dual X-ray absorptiometry.

Results: Median sclerostin concentration in controlled acromegaly patients was significantly lower than in healthy controls (104.5 pg/mL (range 45.7-234.7 pg/mL) vs 140.0 pg/mL (range 44.8-401.6 pg/mL), p < 0.001). Plasma sclerostin levels were not related to age, current growth hormone (GH) or insulin-like factor-1 (IGF-1) levels, gonadal state, treatment modality, remission duration, or BMD, VF presence, severity or progression.

Conclusion: Patients with long-term controlled acromegaly have lower plasma sclerostin levels than healthy controls, as a reflection of decreased osteocyte activity. Further longitudinal studies are needed to establish the course of sclerostin during different phases of disease and its exact effects in acromegalic osteopathy.
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http://dx.doi.org/10.1007/s12020-021-02850-7DOI Listing
August 2021

Clinical Unmet Needs in the Treatment of Adrenal Crisis: Importance of the Patient's Perspective.

Front Endocrinol (Lausanne) 2021 20;12:701365. Epub 2021 Jul 20.

Department of Medicine, Division of Endocrinology, and Center for Endocrine Tumors Leiden (CETL), and European Reference Network on Rare Endocrine Conditions (Endo-ERN), Leiden University Medical Center, Leiden, Netherlands.

Adrenal crisis is the most severe manifestation of adrenal insufficiency (AI), but AI can present with variable signs and symptoms of gradual severity. Despite current hormone replacement strategies, adrenal crisis is still one of the leading causes of mortality in AI patients. Although underlying factors explaining differences in interindividual susceptibility are not completely understood, several subgroups are particularly vulnerable to adrenal crises, such as patients with primary AI, and patients treated for Cushing's syndrome. Currently, the health care professional faces several challenges in the care for AI patients, including the lack of reliable biomarkers measuring tissue cortisol concentrations, absence of a universally used definition for adrenal crisis, and lack of clinical tools to identify individual patients at increased risk. Also from the patient's perspective, there are a number of steps to be taken in order to increase and evaluate self-management skills and, finally, improve health-related quality of life (HR-QoL). In this respect, the fact that inadequate handling of AI patients during stressful situations is a direct consequence of not remembering how to act due to severe weakness and cognitive dysfunction in the context of the adrenal crisis is quite underexposed. In this narrative review, we give an overview of different clinical aspects of adrenal crisis, and discuss challenges and unmet needs in the management of AI and the adrenal crisis from both the doctor's and patient's perspective. For the latter, we use original focus group data. Integration of doctor's and patient's perspectives is key for successful improvement of HR-QoL in patients with AI.
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http://dx.doi.org/10.3389/fendo.2021.701365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329717PMC
July 2021

Apoplexy of microprolactinomas during pregnancy: report of five cases and review of the literature.

Eur J Endocrinol 2021 May 24;185(1):99-108. Epub 2021 May 24.

Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, and Centre de Référence des Maladies Rares de l'Hypophyse, Le Kremlin-Bicêtre, France.

Context: Prolactinomas frequently cause amenorrhoea, galactorrhoea and infertility and require dopamine agonist (DA) treatment to normalize prolactin levels and hence, restore ovulation. The vast majority of female patients harbour microprolactinomas in whom DA treatment is usually discontinued at the time of pregnancy diagnosis and surveillance is generally limited as the symptomatic growth is considered very rare.

Case Descriptions: We report five cases of women harbouring a microprolactinoma in whom symptomatic pituitary apoplexy occurred during pregnancy. Only one necessitated surgery during pregnancy, while the others were treated conservatively by reintroducing DAs in three. A systematic literature review found reports of four additional cases among 20 cases of prolactinomas (both macro- and micro-prolactinomas) complicated by apoplexy during pregnancy.

Conclusion: During pregnancy, pituitary apoplexy may occur in pre-existing microprolactinomas, causing tumour enlargement and headache, which may be self-limiting but may require intervention by re-initation of dopamine agonists or surgery. Our literature review confirms that this clinical event is rare; nevertheless, physicians managing pregnant patients with microprolactinomas must be aware that symptomatic pituitary apoplexy may incidentally occur in all trimesters of pregnancy and require prompt radiological, endocrine and ophthalmological assessment and treatment.
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http://dx.doi.org/10.1530/EJE-21-0145DOI Listing
May 2021

Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure.

Mol Psychiatry 2021 Apr 15. Epub 2021 Apr 15.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 P < 5 × 10), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P < 5 × 10). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (P = 2 × 10). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (P < 10). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
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http://dx.doi.org/10.1038/s41380-021-01087-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517040PMC
April 2021

Serum Inflammation-based Scores in Endocrine Tumors.

J Clin Endocrinol Metab 2021 Sep;106(10):e3796-e3819

Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors Leiden (CETL), Leiden University Medical Center, Leiden, The Netherlands.

Context: Serum inflammation-based scores reflect systemic inflammatory response and/or patients' nutritional status, and may predict clinical outcomes in cancer. While these are well-described and increasingly used in different cancers, their clinical usefulness in the management of patients with endocrine tumors is less known.

Evidence Acquisition: A comprehensive PubMed search was performed using the terms "endocrine tumor," "inflammation," "serum inflammation-based score," "inflammatory-based score," "inflammatory response-related scoring," "systemic inflammatory response markers," "neutrophil-to-lymphocyte ratio," "neutrophil-to-platelet ratio," "lymphocyte-to-monocyte ratio," "Glasgow prognostic score," "neutrophil-platelet score," "Systemic Immune-Inflammation Index," and "Prognostic Nutrition Index" in clinical studies.

Evidence Synthesis: The neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio are the ones most extensively investigated in patients with endocrine tumors. Other scores have also been considered in some studies. Several studies focused in finding whether serum inflammatory biomarkers may stratify the endocrine tumor patients' risk and detect those at risk for developing more aggressive and/or refractory disease, particularly after endocrine surgery.

Conclusions: In this review, we summarize the current knowledge on the different serum inflammation-based scores and their usefulness in predicting the phenotype, clinical aggressiveness, and disease outcomes and prognosis in patients with endocrine tumors. The value of such serum inflammation-based scores in the management of patients with endocrine tumors has been emerging over the last decade. However, further research is necessary to establish useful markers and their cut-offs for routine clinical practice for individual diseases.
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http://dx.doi.org/10.1210/clinem/dgab238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475227PMC
September 2021

Disease and Treatment-Related Burden in Patients With Acromegaly Who Are Biochemically Controlled on Injectable Somatostatin Receptor Ligands.

Front Endocrinol (Lausanne) 2021 15;12:627711. Epub 2021 Mar 15.

Outcomes Research, Health Outcomes Solutions, Winter Park, FL, United States.

Medical treatment for acromegaly commonly involves receiving intramuscular or deep subcutaneous injections of somatostatin receptor ligands (SRLs) in most patients. In addition to side effects of treatment, acromegaly patients often still experience disease symptoms even when therapy is successful in controlling GH and IGF-1 levels. Symptoms and side effects can negatively impact patients' health-related quality of life. In this study, we examine the disease- and treatment-related burden associated with SRL injections as reported through the use of the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ ) and clinician-reported symptom severity through the Acromegaly Index of Severity (AIS). Patients included in this analysis were enrolled in a randomized phase 3 study, were biochemically-controlled (an IGF-1 < 1.3 × the upper limit of normal [ULN] and average GH < 2.5 ng/ml) and receiving SRL injections for ≥6 months with a stable dose of either long-acting octreotide or lanreotide monotherapy for ≥4 months. The sample (N = 91) was 65% female, 91% Caucasian, with a mean [standard deviation (SD)] age of 53 (1) years. Two-thirds of patients reported that they still experience acromegaly symptoms; 82% of these said they experience symptoms all of the time. Three-fourths experienced gastrointestinal (GI) side effects after injections, and 77% experienced treatment-related injection site reactions (ISRs). Patients commonly reported that these interfered with their daily life, leisure, and work activities. Those with higher symptom severity, as measured by the AIS, scored significantly worse on several Acro-TSQ domains: Symptom Interference, GI Interference, Treatment Satisfaction, and Emotional Reaction. Despite being biochemically controlled with injectable SRLs, most patients reported experiencing acromegaly symptoms that interfere with daily life, leisure, and work. GI side effects and ISRs were also common. This study highlights the significant disease burden that still persists for patients with acromegaly that have achieved biochemical control with the use of injectable SRLs.
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http://dx.doi.org/10.3389/fendo.2021.627711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006928PMC
March 2021

Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses.

BMC Med 2021 03 18;19(1):69. Epub 2021 Mar 18.

Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Background: Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease.

Methods: We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions.

Results: We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (- 0.08 standard deviation (SD)[95% confidence interval (CI) - 0.12, - 0.03] in AMV and - 0.03SD [- 0.07, - 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (- 0.04SD [- 0.08, 0.00] in AMV and - 0.05SD [- 0.09, - 0.02] in MR), and lower phospholipids in very large HDL particles (- 0.04SD [- 0.08, 0.002] in AMV and - 0.05SD [- 0.08, - 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures.

Conclusions: Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.
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http://dx.doi.org/10.1186/s12916-021-01939-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971964PMC
March 2021

Outcome Squares Integrating Efficacy and Safety, as Applied to Functioning Pituitary Adenoma Surgery.

J Clin Endocrinol Metab 2021 Aug;106(9):e3300-e3311

Department of Medicine, Division of Endocrinology, Leiden University Medical Centre, ZA Leiden, The Netherlands.

Context: 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.
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http://dx.doi.org/10.1210/clinem/dgab138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372644PMC
August 2021

A physiological glucocorticoid rhythm is an important regulator of brown adipose tissue function.

Mol Metab 2021 05 3;47:101179. Epub 2021 Feb 3.

Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands. Electronic address:

Objective: Brown adipose tissue (BAT) displays a strong circadian rhythm in metabolic activity, but it is unclear how this rhythm is regulated. As circulating levels of corticosterone coincide with the rhythm of triglyceride-derived fatty acid (FA) uptake by BAT, we investigated whether corticosterone regulates BAT circadian rhythm.

Methods: Corticosterone levels were flattened by implanting mice with subcutaneous corticosterone-releasing pellets, resulting in constant circulating corticosterone levels.

Results: Flattened corticosterone rhythm caused a complete loss of circadian rhythm in triglyceride-derived fatty acid uptake by BAT. This effect was independent of glucocorticoid receptor expression in (brown) adipocytes and was not caused by deregulation of clock gene expression or overexposure to glucocorticoids, but rather seemed mediated by reduced sympathetic innervation of BAT. In a mouse model of hyperlipidemia and metabolic syndrome, long-term experimental flattening of corticosterone - and thus rhythm in BAT function - resulted in adiposity.

Conclusions: This study highlights that a physiological rhythm in glucocorticoids is an important regulator of BAT function and essential for the maintenance of metabolic health.
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http://dx.doi.org/10.1016/j.molmet.2021.101179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907824PMC
May 2021

Central serous chorioretinopathy in active endogenous Cushing's syndrome.

Sci Rep 2021 02 2;11(1):2748. Epub 2021 Feb 2.

Department of Ophthalmology, Leiden University Medical Center, Department J3-S, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.

Multiple case series have provided evidence for a relatively high incidence of central serous chorioretinopathy (CSC) in patients with active Cushing's syndrome (CS). We describe the ophthalmological status in detail of consecutive patients with active endogenous CS (either de novo or recurrent active endogenous CS) in this prospective cohort study. All patients underwent complete ophthalmological examination, including multimodal imaging, which was performed shortly after establishing the diagnosis of active CS in hypercortisolemic state. Eleven CS patients (4 men, 7 women) with active hypercortisolism were included. Abnormalities reminiscent of (subclinical) CSC were found in 3 patients. Optical coherence tomography (OCT) revealed macular subretinal fluid in 1 patient, who was diagnosed as having active CSC and was successfully treated with half-dose photodynamic therapy. Two other patients showed CSC-like abnormalities: an unilateral pseudovitelliform lesion on OCT and hyperfluorescent changes on fluorescein angiography in one patient, and unilateral leakage on fluorescein angiography in the other patient. Mean subfoveal choroidal thickness on enhanced depth imaging OCT was 270 ± 40 μm (range, 178 - 357 μm). Retinal abnormalities resembling (subclinical) CSC may be more common than previously thought in patients with active CS, and may exist even in patients without visual complaints. Clinicians should have a low threshold for ophthalmological evaluation in case of a CS patient with visual symptoms since there may be therapeutic opportunities to prevent vision loss.
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http://dx.doi.org/10.1038/s41598-021-82536-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854641PMC
February 2021

Conditioning cortisol in healthy young women - A randomized controlled trial.

Psychoneuroendocrinology 2021 02 1;124:105081. Epub 2020 Dec 1.

Heath Medical and Neuropsychology Unit, Leiden University, Leiden, The Netherlands; Department of Medical Psychology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands. Electronic address:

Background: Learned placebo effects induced by pharmacological conditioning affect immune and endocrine outcomes and may offer new possibilities for clinical applications. Whether or not cortisol is subject to this type of associative learning processes, and whether conditioning may affect responses to stress, is currently unclear.

Method: A randomized placebo-controlled trial was conducted in 48 healthy young women. During acquisition, participants received a pill containing either 100 mg hydrocortisone (unconditioned stimulus) or placebo, paired with a gustatory conditioned stimulus on three consecutive days. During evocation, all participants received placebo paired with the conditioned stimulus, again on three consecutive days. During the third evocation trial, participants underwent a psychosocial stress task. The main outcome parameter salivary cortisol and secondary outcome parameters salivary alpha-amylase, self-reported positive affect and tension, heart rate, and skin conductance level were measured at several time points.

Results: Significant baseline group differences on cortisol were found at several time points, which complicate the interpretation of group differences. During the first evocation session, the conditioned group showed a moderately smaller cumulative decrease in salivary cortisol from baseline than the placebo control group. No significant differences were found between the groups on cortisol during the second and third evocation or in response to stress, nor on other outcome measures.

Conclusion: Although the results provide potential further indications for effects of conditioning on cortisol, baseline differences make it impossible to draw clear conclusions. No indications for possible effects of conditioning on the cortisol stress response or autonomous or affective responses to stress were found.
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http://dx.doi.org/10.1016/j.psyneuen.2020.105081DOI Listing
February 2021

Improvement in Symptoms and Health-Related Quality of Life in Acromegaly Patients: A Systematic Review and Meta-Analysis.

J Clin Endocrinol Metab 2021 01;106(2):577-587

Department of Medicine, Division of Endocrinology, Leiden University Medical Center, ZA Leiden, the Netherlands.

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.
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http://dx.doi.org/10.1210/clinem/dgaa868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823264PMC
January 2021

Pre-operative serum inflammation-based scores in patients with pituitary adenomas.

Pituitary 2021 Jun 24;24(3):334-350. Epub 2020 Nov 24.

Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors Leiden (CETL), Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

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 × 10/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 × 10/L predict multimodal treatment in Cushing's disease. Further studies are needed to confirm these observations.
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http://dx.doi.org/10.1007/s11102-020-01112-5DOI Listing
June 2021

Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis.

Nat Hum Behav 2021 01 16;5(1):113-122. Epub 2020 Nov 16.

Research Institute of Child Development and Education, University of Amsterdam, Amsterdam, the Netherlands.

We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.
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http://dx.doi.org/10.1038/s41562-020-00965-xDOI Listing
January 2021

Effect of anthelmintic treatment on serum free IGF-1 and IGFBP-3: a cluster-randomized-controlled trial in Indonesia.

Sci Rep 2020 11 4;10(1):19023. Epub 2020 Nov 4.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital/Faculty of Medicine Universitas Indonesia, Jl. Diponegoro No. 71, Jakarta Pusat, DKI Jakarta, 10430, Indonesia.

In children, soil-transmitted helminth infections have been linked to poor nutritional status and growth retardation in association with lower levels of IGF-1. In adults, IGF-1 has an anabolic and metabolic function and is related to nutritional status. Here, we assessed the impact of helminth infection on free IGF-1 and its major binding protein, IGFBP-3, in adults. The levels of IGF-1 and IGFBP3 were measured in 1669 subjects aged ≥ 16 years, before and after receiving four rounds of albendazole 400 mg/day or matching placebo for three consecutive days. Helminth infection status was assessed by microscopy (Kato-Katz) and PCR. Serum free IGF-1 level was significantly lower in helminth-infected subjects [mean difference and 95% CI - 0.068 (- 0.103; - 0.033), P < 0.001 after adjustment for age, sex, body mass index, and fasting insulin level]. There was no difference in IGFBP-3 level between helminth infected versus non-infected subjects. In the whole study population, albendazole treatment significantly increased serum free IGF-1 level [estimate and 95% CI 0.031 (0.004; - 0.057), P = 0.024] whereas no effect was found on the IGFBP-3 level. Our study showed that helminth infection in adults is associated with lower free IGF-1 levels but not with IGFBP-3 and albendazole treatment significantly increases free IGF-1 levels in the study population.Clinical Trial Registration: https://www.isrctn.com/ISRCTN75636394 .
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http://dx.doi.org/10.1038/s41598-020-75781-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643058PMC
November 2020

Progression of acromegalic arthropathy in long-term controlled acromegaly patients: 9 years of longitudinal follow-up.

J Clin Endocrinol Metab 2021 01;106(1):188-200

Department of Medicine, Division of Endocrinology, and Center for Endocrine Tumors Leiden, Leiden University Medical Center, ZA, Leiden, the Netherlands.

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.
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http://dx.doi.org/10.1210/clinem/dgaa747DOI Listing
January 2021

Chiasmal herniation following treatment of pituitary macroadenoma.

Pituitary 2021 Feb 15;24(1):68-78. Epub 2020 Oct 15.

Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.

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.
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http://dx.doi.org/10.1007/s11102-020-01088-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864822PMC
February 2021

Healthcare utilization and costs among prolactinoma patients: a cross-sectional study and analysis of determinants.

Pituitary 2021 Feb 6;24(1):79-95. Epub 2020 Oct 6.

Department of Medicine, Division of Endocrinology, Pituitary Center and Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands.

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.
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http://dx.doi.org/10.1007/s11102-020-01089-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864816PMC
February 2021

Postoperative diabetes insipidus: how to define and grade this complication?

Pituitary 2021 Apr 29;24(2):284-291. Epub 2020 Sep 29.

Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, Leiden, Postbox 9600, 2300 RC, The Netherlands.

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) < 1.005, and at least one of the following symptoms: excessive thirst, serum osmolality > 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.
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http://dx.doi.org/10.1007/s11102-020-01083-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966184PMC
April 2021

Continuous Light Does Not Affect Atherosclerosis in APOE*3-Leiden.CETP Mice.

J Biol Rhythms 2020 12 11;35(6):598-611. Epub 2020 Sep 11.

Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands.

Artificial light exposure is associated with dyslipidemia in humans, which is a major risk factor for the development of atherosclerotic cardiovascular disease. However, it remains unclear whether artificial light at night can exacerbate atherosclerosis. In this study, we exposed female APOE*3-Leiden.CETP mice, a well-established model for human-like lipid metabolism and atherosclerosis, to either a regular light-dark cycle or to constant bright light for 14 weeks. Mice exposed to constant light demonstrated a minor reduction in food intake, without any effect on body weight, body composition, or the weight of metabolic organs. Constant light increased the plasma levels of proatherogenic non-high-density lipoprotein (HDL) cholesterol but did not increase the size or severity of atherosclerotic lesions in the aortic root. Mice exposed to constant light did show lower immune cell counts, which could explain the absence of an effect of atherosclerosis despite increased non-HDL cholesterol levels. Behavioral analysis demonstrated variability in the response of mice to the light intervention. Constant light completely blunted behavioral rhythms in some mice, while others extended their behavioral period. However, rhythm strength was not an important determinant of atherosclerosis. Altogether, these results demonstrate that constant bright light does not affect atherosclerosis in APOE*3-Leiden.CETP mice. Whether artificial light exposure contributes to cardiovascular disease risk in humans remains to be investigated.
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http://dx.doi.org/10.1177/0748730420951320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683885PMC
December 2020

The GALANT trial: study protocol of a randomised placebo-controlled trial in patients with a -DOTATATE PET-positive, clinically non-functioning pituitary macroadenoma on the effect of reotide on umour size.

BMJ Open 2020 08 13;10(8):e038250. Epub 2020 Aug 13.

Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The Netherlands.

Introduction: At present, there is no approved medical treatment option for patients with non-functioning pituitary adenoma. A number of open-label studies suggest that treatment with somatostatin analogues may prevent tumour progression. In vivo somatostatin receptor imaging using Ga-DOTATATE PET (PET, positron emission tomography) could help in preselecting patients potentially responsive to treatment. Our aim is to investigate the effect of the somatostatin analogue lanreotide as compared with placebo on tumour size in patients with a Ga-DOTATATE PET-positive non-functioning pituitary macroadenoma (NFMA).

Methods And Analysis: The GALANT study is a multicentre, randomised, double-blind, placebo-controlled trial in adult patients with a suprasellar extending NFMA. Included patients undergo a Ga-DOTATATE PET/CT of the head and tracer uptake is assessed after coregistration with pituitary MRI. Forty-four patients with a Ga-DOTATATE PET-positive NFMA are randomised in a 1:1 ratio between lanreotide 120 mg or placebo, both administered as subcutaneous injections every 28 days for 72 weeks. The primary outcome is the change in cranio-caudal tumour diameter on pituitary MRI after treatment. Secondary outcomes are change in tumour volume, time to tumour progression, change in quality of life and number of adverse events. Final results are expected in the second half of 2021.

Ethics And Dissemination: The study protocol has been approved by the Medical Research Ethics Committee of the Academic Medical Centre (AMC) of the Amsterdam University Medical Centres and by the Dutch competent authority. It is an investigator-initiated study with financial support by Ipsen Farmaceutica BV. The AMC, as sponsor, remains owner of all data. Results will be submitted for publication in a peer-reviewed journal.

Trial Registration Number: NL5136 (Netherlands Trial Register); pre-recruitment.
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http://dx.doi.org/10.1136/bmjopen-2020-038250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430490PMC
August 2020

Endoscopic Surgery for Pituitary Tumors.

Endocrinol Metab Clin North Am 2020 09;49(3):487-503

Department of Neurosurgery, Leiden University Medical Center J11-86, Center for Endocrine Tumors Leiden, PO-Box 9600, Leiden 2300 RC, the Netherlands.

Endoscopic transsphenoidal surgery for pituitary adenoma is a safe and highly effective first-line treatment that is well tolerated by patients. Potential complications are plenty, 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.
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http://dx.doi.org/10.1016/j.ecl.2020.05.011DOI Listing
September 2020

Correction to: Quality of care evaluation in non-functioning pituitary adenoma with chiasm compression: visual outcomes and timing of intervention clinical recommendations based on a systematic literature review and cohort study.

Pituitary 2020 08;23(4):430-431

Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

The original version of the article unfortunately contained an error in Figure 2. The term 'Refer within 3 days' should read 'Refer as soon as possible'. Corrected version of Figure 2 is given below.
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http://dx.doi.org/10.1007/s11102-020-01061-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645562PMC
August 2020

SF-12 or SF-36 in pituitary disease? Toward concise and comprehensive patient-reported outcomes measurements.

Endocrine 2020 10 19;70(1):123-133. Epub 2020 Jun 19.

Department of Medicine, Division of Endocrinology, Pituitary Center and Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands.

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.
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http://dx.doi.org/10.1007/s12020-020-02384-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525280PMC
October 2020

Quality of care evaluation in non-functioning pituitary adenoma with chiasm compression: visual outcomes and timing of intervention clinical recommendations based on a systematic literature review and cohort study.

Pituitary 2020 Aug;23(4):417-429

Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

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 < 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.

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.
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http://dx.doi.org/10.1007/s11102-020-01044-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316692PMC
August 2020

An overview of clinical activities in Endo-ERN: the need for alignment of future network criteria.

Eur J Endocrinol 2020 Aug;183(2):141-148

Department of Medicine, Division of Endocrinology and Centre for Endocrine Tumors Leiden (CETL), Leiden University Medical Centre, Leiden, The Netherlands.

Objective: Given that volumes of patients and interventions are important criteria to qualify as a reference centre (RC) for the European Reference Network on Rare Endocrine Conditions (Endo-ERN), the present study aimed to evaluate the data that were reported in the original application against subsequent assessments of activity and review the criteria that may define RCs using two main thematic groups (MTGs): Pituitary and Thyroid, as examples.

Methods: Review of content in application forms and continuous monitoring data and of a survey distributed to RCs. A list of 'key procedures' for the assessment of performance of RCs was composed with the help of the Pituitary and Thyroid MTG chairs.

Results: In the original application, the number of undefined procedures ranged from 20 to 5500/year (Pituitary) and from 10 to 2700/year (phyroid) between applicants. In the survey, the number of key procedures per centre ranged from 18 to 150/year (Pituitary) and from 20 to 1376/year (Thyroid). The median numbers of new patients reported in the continuous monitoring program were comparable with the application and survey; however, some centres reported large variations.

Conclusions: Monitoring of clinical activity in an ERN requires clear definitions that are optimally aligned with clinical practice, diagnosis registration, and hospital IT systems. This is a particular challenge in the rare disease field where the centre may also provide expert input in collaboration with local hospitals. Application of uniform definitions, in addition to condition-specific clinical benchmarks, which can include patient-reported- as well as clinician-reported outcome measures, is urgently needed to allow benchmarking of care across Endo-ERN.
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http://dx.doi.org/10.1530/EJE-20-0197DOI Listing
August 2020

Feasibility, safety, and outcomes of a stratified fast-track care trajectory in pituitary surgery.

Endocrine 2020 07 2;69(1):175-187. Epub 2020 May 2.

Center for Endocrine Tumors Leiden, Leiden University Medical Center, Leiden, The Netherlands.

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 < 0.001), the total length of stay did not differ (5.3 vs. 5.7 days, 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.
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http://dx.doi.org/10.1007/s12020-020-02308-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343751PMC
July 2020
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