Search

Purpose: To assess the utility of [18F]fluoroethyl-L-tyrosine PET co-registered with magnetic resonance imaging ([18F]FET-PET/MRICR) in patients with difficult-to-localize prolactinoma to inform clinical decision-making and (surgical) treatment planning. Methods: Retrospective cohort study of 17 consecutive patients with prolactinoma undergoing [18F]FET-PET/MRICR between October 2020 and September 2022 for either (1) additional information in case of difficult-to-visualize remnants after prior transsphenoidal surgery (TSS), or pharmacological treatment, or (2) radiological diagnosis in absence of a (clear) adenoma on diagnostic/post-treatment conventional MRI. Results: [18F]FET-PET/MRICR identified a lesion in 14/17 patients, yet failed to identify active lesions in 2 patients with negative conventional MRI despite prolactin > 7.5 times upper limit of normal. [18F]FET-PET/MRICR results were inconclusive in 1 patient due to diffuse tracer uptake 10 weeks post-surgery. [18F]FET-PET/MRICR was completely concordant with a suspected lesion on conventional MRI in 10/17 patients, and partially concordant in 3/17 patients. New foci were identified in 4/17 patients. The [18F]FET-PET/MRICR conclusions influenced clinical shared decision-making in 15/17 patients, of whom 7 patients underwent TSS and 8 refrained from TSS. One patient underwent TSS despite negative [18F]FET-PET/MRICR, and one patient underwent additional imaging. Intraoperative findings corresponded with [18F]FET-PET/MRICR in 5/8 patients, and immunohistochemistry was positive in 5/8 patients. The treatment goal was achieved in 7/8 patients, and remission was achieved in 5/7 patients in whom total resection was considered feasible. Conclusion: [18F]FET-PET/MRICR can be of added value in the preoperative decision-making process for selected patients with difficult-to-localize prolactinoma (remnants), or patients lacking a substrate on conventional MRI. [ABSTRACT FROM AUTHOR]

Background: This retrospective, observational cohort study aimed to determine recovery rate and recovery time of ocular motor nerve palsies (OMP) of third (CN III), fourth (CN IV), or sixth cranial nerves (CN VI)--and associated prognostic factors--in meningioma and pituitary adenoma (PA) patients. Methods: A total of 25 meningioma (28 eyes) and 33 PA patients (36 eyes), treated at the Leiden University Medical Center in the Netherlands from January 1, 1978 to January 31, 2021, were included. OMPs were evaluated according to a newly created recovery scale using onclinical and orthoptic examinations, which were performed every 3--4 months until palsy recovery, or at 18 months follow-up. Results: Recovery rates of CN III (meningioma 23.5% vs PA 92.3%), CN IV (meningioma 20% vs PA 100%), and CN VI (meningioma 60% vs PA 100%) palsies were observed at 18 months follow-up, with differences between the 2 tumor types being observed in the treated patients only. Median recovery time of all OMPs combined was significantly longer in meningioma patients (37.9 ± 14.3 months vs 3.3 ± 0.1 months; P, 0.001). No significant protective or risk factors for recovery rate or time were identified. Conclusions: OMP recovery rates in treated patients were more favorable in patients with PA compared with patients with meningiomas, independent of OMP cause. With these new insights in OMP recovery, more accurate prognoses and appropriate follow-up strategies can be determined for meningioma and PA patients with OMPs. [ABSTRACT FROM AUTHOR]

Objective: To report our experience with 18F‐fluoro‐ethyl‐tyrosine (FET) positron emission tomography‐computed tomography (PET‐CT) co‐registered with magnetic resonance imaging (MRI) (FET‐PET/MRICR) in the care trajectory for persistent acromegaly. Design: Prospective case series. Patients: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options. Measurements: FET‐PET/MRICR was used to support decision‐making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery. Results: FET‐PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET‐PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET‐PET/MRICR identified suggestive new foci in four other patients. Surgical re‐exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET‐PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF‐1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients. Conclusions: In patients with persisting acromegaly without a clear surgical target on MRI, FET‐PET/MRICR is a new tracer to provide additional information to aid decision‐making by the multidisciplinary pituitary team. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate patients with prolactinoma treated surgically in a time when elective prolactinoma surgery became routine in our center, using a comprehensive outcome set, focusing on preoperative assessments, surgical outcomes, and health-related quality of life (HR-QoL)., Methods: Cohort of consecutive patients with prolactinoma undergoing surgery between January 2021 and August 2023. Clinical data were collected during multidisciplinary team (MDT) meetings/from medical records at distinct timepoints: (1) pre-surgery, (2) two weeks post-surgery, (3) six months post-surgery, and (4) follow-up (median 15.0 (10.0-24.8 months). HR-QoL was measured using the Leiden Bothers and Needs Pituitary (LBNQ-P) questionnaire. Data were described for all patients, and patients undergoing elective total resection, with additional subgroups of (a) patients undergoing a high-probability-first-total-resection, and (b) reoperations aiming for total resection., Results: One hundred surgically treated patients with prolactinoma were included (72 female). Dopamine agonist intolerance was the most frequent indication (n=68). The surgical goal (debulking/total resection) was achieved in 90% of patients. Long-term complications occurred in 4% of patients. Seventy-eight patients underwent an elective total resection, achieving remission in 91%. The subsets of preoperatively estimated high-probability-first-total-resections (n=52), and reoperations (n=9), achieved remission in 92% and 89%, respectively. LBNQ-P Total Bothers and Total Needs scores improved significantly after surgery (p<0.001, Δ-3.4 (IQR -14.4- -0.9) and p=0.006, Δ-1.8 (IQR -11.9-1.3), respectively., Conclusion: High remission rates were achieved, improving HR-QoL, evidencing (repeat) prolactinoma surgery is effective in an experienced pituitary center, as highlighted in the most recent guideline (2023)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To report our experience with 18 F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRI CR ) in the care trajectory for persistent acromegaly., Design: Prospective case series., Patients: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options., Measurements: FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery., Results: FET-PET/MRI CR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRI CR was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRI CR identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRI CR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients., Conclusions: In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRI CR is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team., (© 2024 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.)

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., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Small for gestational age (SGA) neonates are at increased risk of mortality and morbidity, including necrotizing enterocolitis (NEC), but detailed information on the incidence and risk factors of NEC in SGA neonates is lacking., Objective: This study aims to estimate the incidence of NEC in a large cohort of SGA neonates, compared to appropriate for gestational age (AGA) neonates., Methods: We included all SGA neonates without congenital malformations admitted to our neonatal nursery between 2004 and 2013. Neonates in the SGA group were matched for gestational age with a control group of AGA neonates admitted during the same study period. We recorded the occurrence of NEC and studied the association with SGA and other potential risk factors., Results: A total of 475 SGA neonates were matched for gestational age at birth to 475 control AGA neonates. The incidence of NEC in the SGA group was 3.2% (15/475) versus 1.3% (6/475) in the AGA group (OR 2.55, 95% CI 0.98-6.63, p = 0.047). The incidence of NEC in the subgroups with mild, moderate and severe SGA was 2.3% (5/215), 4.7% (5/1.07) and 3.2% (5/153), respectively (p = 0.531)., Conclusions: The risk of development of NEC is more than twofold increased in SGA neonates compared to AGA neonates. We found no association between the severity of SGA and NEC., (© 2013 S. Karger AG, Basel.)