Background: Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up... Show moreBackground: Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment.Aims: To report on outcomes of ETSS in a cohort of prolactinomas.Methods: Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 +/- 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation.Results: Median preoperative prolactin levels were 166 (98-837 mu g/L; males 996 [159-2145 mu g/L] vs. females 129 [84-223 mu g/L], p <0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p <0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p <0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p = 0.006. Long-term remission (i.e., DA-free prolactin level <1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p = 0.002). Transient DI (n = 29, 21.2%) was the most frequent complication.Conclusions: Despite high proportions of macroprolactinoma and KNOSP 3-4, long-term remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.(c) 2023 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved. Show less
Background. Growth-hormone-producing pituitary adenomas have variable likelihood for biochemical remission (BR). During preoperative counseling, individual estimated surgical likelihoods/risks... Show moreBackground. Growth-hormone-producing pituitary adenomas have variable likelihood for biochemical remission (BR). During preoperative counseling, individual estimated surgical likelihoods/risks should be balanced against alternative (medical) treatments, which is necessary for accurate outcome presentation. Preoperative estimation of BR or total resection (TR) likelihoods have not been reported, resulting in extrapolation of individual outcomes. Aims. To share an innovative outcome reporting paradigm by integrating surgical decision-making, and expected/realized results, resulting from the Value-Based Health Care (VBHC) care path with periodical performance evaluation and care innovation cycle. Methods. Prospective cohort study of consecutive patients with acromegaly undergoing surgery (January 2016-December 2020; postoperative follow-up >= 6 months) reporting on both classic, and novel innovative outcome evaluations. Results. Fifty eight patients (66 procedures) were included. Intended TR was achieved in 34/50 procedures, whereas intended debulking was achieved in 15/16 procedures. 38/66 procedures resulted in BR, and 4 procedures resulted in permanent complications. Achieving intended surgical goal was estimated preoperatively as likely in 33 (goal achieved (GA) in 28/33), potentially in 27 (GA in 19/27), and unlikely in 6 procedures (GA in 2/6). Integrated Outcome Square 1 (IOQ1) -intended effect achieved without complications- was achieved in 46/66 patients. Conclusion. Implementation of the developed quality process positively affects preopparticularly in complex patients for whom preoperative chances are not fully reflected by tumor size and KNOSP grade, e.g., reoperations, or other challenging circumstances identified during preoperative counseling. Through repeated evaluations, our own team's reserved. Show less
PurposeTo describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery.MethodsRetrospective observational cohort study of consecutive patients with... Show morePurposeTo describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery.MethodsRetrospective observational cohort study of consecutive patients with prolactinoma undergoing surgery from 2017 to 2019 at the referral center (RC), prior to surgery being considered a viable treatment option (i.e. PRolaCT study). Demographics and clinical data (type and duration of pretreatment and surgical indications, goals, and outcomes) were collected from patient records. Care trajectories were divided into three phases: (1) diagnosis and initial treatment, (2) endocrine treatment at the RC, and (3) surgical treatment.Results40 patients were included (31 females (77.5%), median age 26.5 (14-63) years. Indications for surgery were dopamine agonist (DA) intolerance (n = 31, 77.5%), resistance (n = 6, 15.0%), and patient/physician preference (n = 3, 7.5%). Patients were pretreated with DA (n = 39 (97.5%)), and surgery (n = 3 (7.5%)). Median disease duration at surgery was 4 (0-27) years. Primary surgical goal was total resection in 38 patients (95.0%), of which biochemical remission was achieved 6 months postoperatively in 23 patients (62.2%), and clinical remission in 6 patients (16.2%), missing data n = 1.ConclusionCare trajectories were highly individualized based on patient and tumor characteristics, as well as the multidisciplinary team's assessment (need for alternative treatment, surgical chances and risks). Most patients were pretreated pharmacologically and had broad variation in timing of referral, undergoing surgery as last-resort treatment predominantly due to DA intolerance. High quality imaging and multidisciplinary consultations with experienced neurosurgeons and endocrinologists enabling treatment tailored to patients' needs were prerequisites for adequate counseling in treatment of patients with prolactinoma. Show less
PurposeTo describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery.MethodsRetrospective observational cohort study of consecutive patients with... Show morePurposeTo describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery.MethodsRetrospective observational cohort study of consecutive patients with prolactinoma undergoing surgery from 2017 to 2019 at the referral center (RC), prior to surgery being considered a viable treatment option (i.e. PRolaCT study). Demographics and clinical data (type and duration of pretreatment and surgical indications, goals, and outcomes) were collected from patient records. Care trajectories were divided into three phases: (1) diagnosis and initial treatment, (2) endocrine treatment at the RC, and (3) surgical treatment.Results40 patients were included (31 females (77.5%), median age 26.5 (14-63) years. Indications for surgery were dopamine agonist (DA) intolerance (n = 31, 77.5%), resistance (n = 6, 15.0%), and patient/physician preference (n = 3, 7.5%). Patients were pretreated with DA (n = 39 (97.5%)), and surgery (n = 3 (7.5%)). Median disease duration at surgery was 4 (0-27) years. Primary surgical goal was total resection in 38 patients (95.0%), of which biochemical remission was achieved 6 months postoperatively in 23 patients (62.2%), and clinical remission in 6 patients (16.2%), missing data n = 1.ConclusionCare trajectories were highly individualized based on patient and tumor characteristics, as well as the multidisciplinary team's assessment (need for alternative treatment, surgical chances and risks). Most patients were pretreated pharmacologically and had broad variation in timing of referral, undergoing surgery as last-resort treatment predominantly due to DA intolerance. High quality imaging and multidisciplinary consultations with experienced neurosurgeons and endocrinologists enabling treatment tailored to patients' needs were prerequisites for adequate counseling in treatment of patients with prolactinoma. Show less
Wolters, F.; Middendorp, H. van; Bergh, O. Van Den; Biermasz, N.R.; Meijer, O.C.; Evers, A.W.M. 2023
Purpose: To describe quality and outcomes of patient-reported outcome (PRO) measures (PROMs) used in patients with refractory hormone-producing pituitary adenomas, and to provide an overview of... Show morePurpose: To describe quality and outcomes of patient-reported outcome (PRO) measures (PROMs) used in patients with refractory hormone-producing pituitary adenomas, and to provide an overview of PROs in these challenging pituitary adenomas. Methods: Three databases were searched for studies reporting on refractory pituitary adenomas. For the purpose of this review, refractory adenomas were defined as tumors resistant to primary therapy. General risk of bias was assessed using a component approach and the quality of PROM reporting was assessed using the International Society for Quality of Life Research (ISOQOL) criteria.Results: 20 studies reported on PROMs in refractory pituitary adenomas, using 14 different PROMs, of which 4 were disease specific (median general risk of bias score: 33.5% (range 6-50%) and ISOQOL score: 46% (range 29-62%)). SF-36/RAND-36 and AcroQoL were most frequently used. Health-related quality of life in refractory patients (measured by AcroQoL, SF-36/Rand-36, Tuebingen CD-25, and EQ-5D-5L) varied greatly across studies, and was not always impaired compared to patients in remission. Conclusion: There is a scarcity of data on PROs in the subset of pituitary adenomas that is more difficult to treat, e.g., refractory and these patients are difficult to isolate from the total cohort. The patients' perspective on quality of life, therefore, remains largely unknown in refractory patients. Thus, PROs in refractory pituitary adenomas require adequate analysis using properly reported disease specific PROMs in large cohorts to enable appropriate interpretation for use in clinical practice. Show less
Rare endocrine conditions present specific diagnostic and management challenges for healthcare providers, one of which is the understudied transition of care. Despite the need for guidance... Show moreRare endocrine conditions present specific diagnostic and management challenges for healthcare providers, one of which is the understudied transition of care. Despite the need for guidance regarding transition, consensus on structured and protocolled approaches is lacking. Therefore, we aimed to map the current clinical practice and identify unmet needs regarding transition of care for patients with pituitary disease in the reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN). A survey-based, cross-sectional study using the EU Survey tool was performed and completed by 46 physicians (n) from 30 RCs (N). Transition is a common practice among RCs (n = 44/46), usually accomplished by a multidisciplinary team meeting (N = 20/30). Criteria for start and end of transition were defined in half of the RCs, with 16.7% of centers providing dissimilar answers. Transition readiness was assessed by >75% of the RCs, mostly by unvalidated means (e.g. subjective opinions, informal consultations). Pituitary-specific transition assessment tool was applied in one RC only. Transition protocols were present in only 9% of RCs, while in many RCs, transition decisions were taken in combined adult-pediatric meetings or based on clinicians' personal judgment. A minority of physicians evaluated the effectiveness of transition-related interventions (n = 11/46) or medical outcomes (n = 8/46). Patient-reported outcome measures were infrequently used (n = 4/46). Identified unmet needs included the development of guidelines (n = 5/46) and EU-wide approach (n = 2/46). This study exemplifies the unmet needs for a structural definition of the transition period and transition management for patients with rare hypothalamic and pituitary conditions from healthcare providers' perspective. Show less
Najafabadi, A.H.Z.; Meulen, M. van der; Zurita, A.L.P.; Ahmed, S.F.; Furth, W.R. van; Charmandari, E.; ... ; Biermasz, N.R. 2023
ObjectiveThe European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, including care for pituitary adenoma patients. As surgery... Show moreObjectiveThe European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, including care for pituitary adenoma patients. As surgery is the mainstay of treatment, we aimed to describe the current surgical practice and published surgical outcomes of pituitary adenoma within Endo-ERN. Design and MethodsSystematic review and meta-analysis of studies reporting surgical outcomes of pituitary adenoma patients within Endo-ERN MTG6 pituitary reference centers between 2010 and 2019. A survey was completed by reference centers on their current surgical practice. Results A total of 18 out of 43 (42%) reference centers located in 7 of the 20 (35%) MTG6-represented countries published 48 articles. Remission rates were 50% (95% CI: 42-59) for patients with acromegaly, 68% (95% CI: 60-75) for Cushing's disease, and 53% (95% CI: 39-66%) for prolactinoma. Gross total resection was achieved in 49% (95% CI: 37-61%) of patients and visual improvement in 78% (95% CI: 68-87). Mortality, hemorrhage, and carotid injury occurred in less than 1% of patients. New-onset hypopituitarism occurred in 16% (95% CI: 11-23), transient diabetes insipidus in 12% (95% CI: 6-21), permanent diabetes insipidus in 4% (95% CI: 3-6), syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 9% (95% CI: 5-14), severe epistaxis in 2% (95% CI: 0-4), and cerebrospinal fluid leak in 4% (95% CI: 2-6). Thirty-five (81%) centers completed the survey: 54% were operated endoscopically and 57% were together with an ENT surgeon. ConclusionThe results of this study could be used as a first benchmark for the outcomes of pituitary adenoma surgery within Endo-ERN. However, the heterogeneity between studies in the reporting of outcomes hampers comparability and warrants outcome collection through registries. Show less
Wolters, F.; Middendorp, H. van; Bergh, O. van den; Biermasz, N.R.; Meijer, O.C.; Evers, A.W.M. 2023
Background: The hormone cortisol plays important roles in human circadian and stress physiology and is an interesting target for interventions. Cortisol varies not only in response to stress but... Show moreBackground: The hormone cortisol plays important roles in human circadian and stress physiology and is an interesting target for interventions. Cortisol varies not only in response to stress but also as part of a diurnal rhythm. It shows a particularly sharp increase immediately after awakening, the cortisol awakening response (CAR). Cortisol can be affected by medication, but it is less clear whether it can also be affected by learning. Animal studies have consistently shown that cortisol can be affected by pharmacological conditioning, but the results in humans have been mixed. Other studies have suggested that conditioning is also possible during sleep and that the diurnal rhythm can be conditioned, but these findings have not yet been applied to cortisol conditioning. Objective: The objective of our study was to introduce a novel avenue for conditioning cortisol: by using the CAR as an unconditioned response and using scent conditioning while the participant is asleep. This study investigates an innovative way to study the effects of conditioning on cortisol and the diurnal rhythm, using a variety of devices and measures to make measurement possible at a distance and at unusual moments. Methods: The study protocol takes 2 weeks and is performed from the participant's home. Measures in week 1 are taken to reflect the CAR and waking under baseline conditions. For the first 3 nights of week 2, participants are exposed to a scent from 30 minutes before awakening until their normal time of awakening to allow the scent to become associated with the CAR. On the final night, participants are forced to wake 4 hours earlier, when cortisol levels are normally low, and either the same (conditioned group) or a different (control group) scent is presented half an hour before this new time. This allows us to test whether cortisol levels are higher after the same scent is presented. The primary outcome is the CAR, assessed by saliva cortisol levels, 0, 15, 30, and 45 minutes after awakening. The secondary outcomes are heart rate variability, actigraphy measures taken during sleep, and self-reported mood after awakening. To perform manipulations and measurements, this study uses wearable devices, 2 smartphone apps, web-based questionnaires, and a programmed scent device. Results: We completed data collection as of December 24, 2021. Conclusions: This study can provide new insights into learning effects on cortisol and the diurnal rhythm. If the procedure does affect the CAR and associated measures, it also has potential clinical implications in the treatment of sleep and stress disorders. Trial Registration: Netherlands Trial Register NL58792.058.16; https://trialsearch.who.int/Trial2.aspx?TrialID=NL7791 International Registered Report Identifier (IRRID): DERR1-10.2196/38087 Show less
Samson, S.L.; Nachtigall, L.B.; Fleseriu, M.; Jensterle, M.; Manning, P.J.; Elenkova, A.; ... ; Melmed, S. 2022
Objective: The objective of this study is to report results from the open-label extension (OLE) of the OPTIMAL trial of oral octreotide capsules (OOC) in adults with acromegaly, evaluating the long... Show moreObjective: The objective of this study is to report results from the open-label extension (OLE) of the OPTIMAL trial of oral octreotide capsules (OOC) in adults with acromegaly, evaluating the long-term durability of therapeutic response. Design: The study design is an OLE of a double-blind placebo-controlled (DPC) trial. Methods: Patients completing the 36-week DPC period on the study drug (OOC or placebo) or meeting predefined withdrawal criteria were eligible for OLE enrollment at 60 mg/day OOC dose, with the option to titrate to 40 or 80 mg/day. The OLE is ongoing; week 48 results are reported. Results: Forty patients were enrolled in the OLE, 20 each having received OOC or placebo, with 14 and 5 patients completing the DPC period as responders, respectively. Ninety percent of patients completing the DPC period on OOC and 70% of those completing on placebo completed 48 weeks of the OLE. Maintenance of response in the OLE (i.e. insulin-like growth factor I (IGF1) <= 1.0 x upper limit of normal (ULN)) was achieved by 92.6% of patients who responded to OOC during the DPC period. Mean IGF1 levels were maintained between the end of the DPC period (0.91 x ULN; 95% CI: 0.784, 1.045) and week 48 of the OLE (0.90 x ULN; 95% CI: 0.750, 1.044) for those completing the DPC period on OOC. OOC safety was consistent with previous findings, with no increased adverse events (AEs) associated with the higher dose and improved gastrointestinal tolerability observed over time. Conclusions: Patients with acromegaly maintained long-term biochemical response while receiving OOC, with no new AEs observed with prolonged OOC exposure. Show less
Fallo, F.; Dalmazi, G. di; Beuschlein, F.; Biermasz, N.R.; Castinetti, F.; Elenkova, A.; ... ; Reincke, M. 2022
Endogenous/exogenous Cushing's syndrome is characterized by a cluster of systemic manifestations of hypercortisolism, which cause increased cardiovascular risk. Its biological basis is... Show moreEndogenous/exogenous Cushing's syndrome is characterized by a cluster of systemic manifestations of hypercortisolism, which cause increased cardiovascular risk. Its biological basis is glucocorticoid excess, acting on various pathogenic processes inducing cardiovascular damage. Hypertension is a common feature in Cushing's syndrome and may persist after normalizing hormone excess and discontinuing steroid therapy. In endogenous Cushing's syndrome, the earlier the diagnosis the sooner management can be employed to offset the deleterious effects of excess cortisol. Such management includes combined treatments directed against the underlying cause and tailored antihypertensive drugs aimed at controlling the consequences of glucocorticoid excess. Experts on endocrine hypertension and members of the Working Group on Endocrine Hypertension of the European Society of Hypertension (ESH) prepared this Consensus document, which summarizes the current knowledge in epidemiology, genetics, diagnosis, and treatment of hypertension in Cushing's syndrome. Show less
The metabolic and cardiovascular clinical manifestations in patients with Cushing's syndrome (CS) are generally well known. However, recent studies have broadened the perspective of the effects of... Show moreThe metabolic and cardiovascular clinical manifestations in patients with Cushing's syndrome (CS) are generally well known. However, recent studies have broadened the perspective of the effects of hypercortisolism, showing that both endogenous and exogenous glucocorticoid excess alter brain functioning on several time scales. Consequently, cognitive deficits and neuropsychological symptoms are highly prevalent during both active CS and CS in remission, as well as during glucocorticoid treatment. In this review, we discuss the effects of endogenous hypercortisolism and exogenously induced glucocorticoid excess on the brain, as well as the prevalence of cognitive and neuropsychological deficits and their course after biochemical remission. Furthermore, we propose possible mechanisms that may underly neuronal changes, based on experimental models and in vitro studies. Finally, we offer recommendations for future studies. Show less
Testosterone therapy is the cornerstone in the care of men with hypogonadism and transgender males. Gel and intramuscular injections are most frequently used and are registered and included in the... Show moreTestosterone therapy is the cornerstone in the care of men with hypogonadism and transgender males. Gel and intramuscular injections are most frequently used and are registered and included in the international guidelines. The specific preparation should be selected according to the patient's preference, cost, availability, and formulation-specific properties. As the majority of men with hypogonadism and transgender males require lifelong treatment with testosterone, it is important to utilize a regimen that is effective, safe, inexpensive, and convenient to use with optimal mimicking of the physiological situation. This systematic review reviews current literature on differences between the three most used testosterone preparations in adult men with hypogonadism and transgender males. Although it appeared hardly any comparative studies have been carried out, there are indications of differences between the preparations, for example, on the stability of testosterone levels, hematocrit, bone mineral density, and patient satisfaction. However, there are no studies on the effects of testosterone replacement on endpoints such as cardiovascular disease in relation to hematocrit or osteoporotic fractures in relation to bone mineral density. The effect of testosterone therapy on health-related quality of life is strongly underexposed in the reviewed studies, while this is a highly relevant outcome measure from a patient perspective. In conclusion, current recommendations on testosterone treatment appear to be based on data primarily from non-randomized clinical studies and observational studies. The availability of reliable comparative data between the different preparations will assist in the process of individual decision-making to choose the most suitable formula. Show less
Dekkers, A.J.; Vries, F. de; Najafabadi, A.Z.H.; Hoeven, E.M. van der; Verstegen, M.J.T.; Pereira, A.M.; ... ; Biermasz, N.R. 2022
Purpose: Value-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice... Show morePurpose: Value-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice we evaluated healthcare costs and cost drivers in perioperative care for pituitary tumour patients. Methods: We retrospectively assessed financial and clinical data for surgical treatment up to the first year after surgery of pituitary tumour patients treated between 2015 and 2018 in a Dutch tertiary referral centre. Multivariable regression analyses were performed to identify determinants of higher costs. Results: 271 patients who underwent surgery were included. Mean total costs (SD) were euro16339 (13573) per patient, with the following cost determinants: surgery time (euro62 per minute; 95% CI: 50, 74), length of stay (euro1331 per day; 95% CI 1139, 1523), admission to higher care unit (euro12154 in total; 95% CI 6413, 17895), emergency surgery (euro10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (euro14232; 95% CI 9667, 18797). Intradural (euro7128; 95% CI 10421, 23836) and combined transsphenoidal/transcranial surgery (B: 38494; 95% CI 29191, 47797) were associated with higher costs than standard. Further, higher costs were found in these baseline conditions: Rathke's cleft cyst (euro9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (euro19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (euro14613; 95% CI 7613, 21613) and dependent functional status (euro12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were euro8879 (3210) and with complications euro17551 (14250). Conclusions: Length of hospital stay, and complications are the main drivers of costs in perioperative pituitary tumour healthcare as were some baseline features, e.g. larger tumors, cysts and dependent functional status. Costs analysis may correspond with healthcare resource utilization and guide further individualized care path development and capacity planning. Show less
Purpose: Acromegalic arthropathy is a well-known phenomenon, occurring in most patients regardless of disease status. To date, solely hips, knees, hands, and spinal joints have been... Show morePurpose: Acromegalic arthropathy is a well-known phenomenon, occurring in most patients regardless of disease status. To date, solely hips, knees, hands, and spinal joints have been radiographically assessed. Therefore, this study aimed to assess the prevalence of joint symptoms and radiographic osteoarthritis (OA) of new, and established peripheral joint sites in well-controlled acromegaly. Methods: Fifty-one acromegaly patients (56% female, mean age 64 +/- 12 years) in long-term remission for 18.3 years (median, IQR 7.2-25.4) were included. Nineteen patients currently received pharmacological treatment. Self-reported joint complaints were assessed using standardized interviews. Self-reported disability of the upper and lower limbs, and health-related quality of life (HR-QoL) were evaluated using validated questionnaires. Radiographic OA [defined as Kellgren & Lawrence (KL) >= 2] was scored using (modified) KL methods. Results: Radiographic signs of OA were present in 46 patients (90.2%) with >= 2 joints affected in virtually all of these patients (N = 44; 95.7%). Radiographic MTP1 OA was as prevalent as radiographic knee OA (N = 26, 51.0%), and radiographic glenohumeral OA was similarly prevalent as hip OA [N = 21 (41.2%) vs. N = 24 (47.1%)]. Risk factors for radiographic glenohumeral OA were higher pre-treatment IGF-1 levels [OR 1.06 (1.01-1.12), P = 0.021], and current pharmacological treatment [OR 5.01 (1.03-24.54), P = 0.047], whereas no risk factors for MTP1 joint OA could be identified. Conclusion: Similar to previously-assessed peripheral joints, clinical and radiographic arthropathy of the shoulder and feet were prevalent in controlled acromegaly. Further studies on adequate management strategies of acromegalic arthropathy are needed. Show less
Purpose: To report the first experience of our multidisciplinary team with functional imaging using C-11-methionine positron emission tomography-computed tomography (C-11-methionine PET-CT) co... Show morePurpose: To report the first experience of our multidisciplinary team with functional imaging using C-11-methionine positron emission tomography-computed tomography (C-11-methionine PET-CT) co-registered with MRI (Met-PET/MRICR) in clinical decision making and surgical planning of patients with difficult to treat prolactinoma. Methods: In eighteen patients with prolactinoma, referred to our tertiary referral centre because of intolerance or resistance for dopamine agonists (DA), Met-PET/MRICR was used to aid decision-making regarding therapy. Results: Met-PET/MRICR was positive in 94% of the patients. MRI and Met-PET/MRICR findings were completely concordant in five patients, partially concordant in nine patients, and non-concordant in four patients. In five patients Met-PET/MRICR identified lesion(s) that were retrospectively also visible on MRI. Met-PET/MRICR was false negative in one patient, with a cystic adenoma on conventional MRI. Thirteen patients underwent transsphenoidal surgery, with nine achieving full biochemical remission, two clinical improvement and near normalized prolactin levels, and one patient clinical improvement with significant tumour reduction. Hence, nearly all patients (94%) were considered to have a positive outcome. Permanent complication rate was low. Three patients continued DA, two patients have a wait and scan policy. Conclusion: Met-PET/MRICR can provide additional information to guide multidisciplinary preoperative and intraoperative decision making in selected cases of prolactinoma. This approach resulted in a high remission rate with a low rate of complications in our expert centre. Show less
Haalen, F.M. van; Kaya, M.; Pelsma, I.C.M.; Dekkers, O.M.; Biermasz, N.R.; Cannegieter, S.C.; ... ; Endo-ERN Cushing Thrombosis study 2022
Background Cushing's syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in... Show moreBackground Cushing's syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed. Results The majority of the RCs provided thromboprophylaxis to patients with CS (n = 23/25), although only one center had a standardized thromboprophylaxis protocol (n = 1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n = 11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n = 15/23). Factors influencing the initiation of thromboprophylaxis were 'medical history of VTE' (n = 15/23) and 'severity of hypercortisolism' (n = 15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n = 23/23). Postoperatively, the majority of RCs reported 'severe immobilization' as an indication to start thromboprophylaxis in patients with CS (n = 15/25). Most RCs (n = 19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n = 23/25). About half of these RCs (n = 12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n = 15/23) included 'reduction of VTE risk' as a goal of treatment. Conclusions There is a large practice variation regarding thromboprophylaxis management and perioperative medical treatment in patients with CS, even in Endo-ERN RCs. Randomized controlled trials are needed to establish the optimal prophylactic anticoagulant regimen, carefully balancing the increased risk of (perioperative) bleeding, and the presence of additional risk factors for thrombosis. Show less
Background: Despite biochemically responding to injectable somatostatin receptor ligands (iSRLs), many patients with acromegaly experience treatment burdens. We aimed to assess maintenance of... Show moreBackground: Despite biochemically responding to injectable somatostatin receptor ligands (iSRLs), many patients with acromegaly experience treatment burdens. We aimed to assess maintenance of biochemical response and symptomatic control with oral octreotide capsules versus iSRLs in patients with acromegaly who previously tolerated and responded to both. Methods: This global, open-label, randomised controlled phase 3 trial was done in 29 clinical sites in Austria, France, Germany, Hungary, Italy, Lithuania, Russia, Serbia, Spain, and the USA. Eligible patients were adults aged 18-75 years with acromegaly who were receiving iSRLs (long-acting octreotide or lanreotide autogel) for at least 6 months before baseline with a stable dose for at least 4 months, and were deemed to be biochemically responding (insulin-like growth factor I [IGF-I] <1middot3 x upper limit of normal [ULN] and mean integrated growth hormone <2middot5 ng/mL). In the 26-week run-in phase, all patients received oral octreotide (40 mg a day, optional titration to 60 or 80 mg a day). Eligibility for the randomised treatment phase was completion of the run-in phase as a biochemical responder (IGF-I <1middot3 x ULN and mean integrated growth hormone <2middot5 ng/mL at week 24) and investigator assessment of acromegaly being adequately controlled. Patients were randomly assigned (3:2) to oral octreotide capsules or iSRL at the same dose and interval as before enrolment. Randomisation and drug dispensing were conducted through a qualified randomisation service provider (eg, interactive web or voice response system). The primary endpoint was a non-inferiority assessment (margin -20 percentage points) of proportion of participants maintaining biochemical response throughout the randomised treatment phase (IGF-I <1middot3 x ULN using time-weighted average; assessed by comparing the lower bound of the 2-sided 95% CI for the difference in biochemical response between groups). IGF-I was assessed once a month during the run-in and randomised treatment phases (single sample). Efficacy and safety assessments were performed on the randomised population. This trial is registered with ClinicalTrials.gov, NCT02685709. Findings: Between Feb 11, 2016, and Aug 20, 2020, 218 patients were assessed for eligibility. 72 patients were excluded, and 146 participants were enrolled into the run-in phase. 116 patients completed the run-in phase and 30 participants discontinued treatment. 92 participants were randomly assigned to oral octreotide (n=55) or iSRL (n=37). 50 (91%) of 55 participants who received oral octreotide (95% CI 44-53) and 37 (100%) of 37 participants who received iSRLs (34-37) maintained biochemical response. The lower bound of the 2-sided 95% CI for the adjusted difference in proportions between the two treatment groups achieved the prespecified non-inferiority criterion of -20% (95% CI -19middot9 to 0middot5). 19 (35%) of 55 participants in the oral octreotide group and 15 (41%) of 37 participants in the iSRL group had treatment-related adverse events; the most common of which in both groups were gastrointestinal. Interpretation: Oral octreotide was non-inferior to iSRL treatment, and might be a favourable alternative to iSRLs for many patients with acromegaly. Show less
