We report a case of a 75-year-old patient with hypopituitarism, bitemporal visual field deficits and a parasellar mass on pituitary MRI. During surgery, suspicion was raised that a non-functioning... Show moreWe report a case of a 75-year-old patient with hypopituitarism, bitemporal visual field deficits and a parasellar mass on pituitary MRI. During surgery, suspicion was raised that a non-functioning pituitary adenoma was accompanied by an abutting diaphragm sellae meningioma, which was confirmed at pathological examination. In retrospect, the initial MRI suggested two separate tumours on the basis of differing densities but this distinction was not seen on the last preoperative MRI. Show less
Bos, M.M.; Heemst, D. van; Donga, E.; Mutsert, R. de; Rosendaal, F.R.; Blauw, G.J.; ... ; Noordam, R. 2019
PurposeNon-functioning pituitary adenomas (NFPA) have a substantial impact on patients' health status, yet research on the extent of healthcare utilization and costs among these patients is scarce.... Show morePurposeNon-functioning pituitary adenomas (NFPA) have a substantial impact on patients' health status, yet research on the extent of healthcare utilization and costs among these patients is scarce. The objective was to determine healthcare usage, associated costs, and their determinants among patients treated for an NFPA.MethodsIn a cross-sectional study, 167 patients treated for an NFPA completed four validated questionnaires. Annual healthcare utilization and associated costs were assessed through the medical consumption questionnaire (MTA iMCQ). In addition, the Leiden Bother and Needs Questionnaire for pituitary patients (LBNQ-Pituitary), Short Form-36 (SF-36), and EuroQol (EQ-5D) were administered. Furthermore, age, sex, endocrine status, treatment, and duration of follow-up were extracted from the medical records. Associations were analyzed using logistic/linear regression.ResultsAnnual healthcare utilization included: consultation of an endocrinologist (95% of patients), neurosurgeon (14%), and/or ophthalmologist (58%). Fourteen percent of patients had 1 hospitalization(s) and 11% 1 emergency room visit(s). Mean overall annual healthcare costs were Euro 3040 (SD 6498), highest expenditures included medication (31%), inpatient care (28%), and specialist care (17%). Factors associated with higher healthcare utilization and costs were greater self-perceived disease bother and need for support, worse mental and physical health status, younger age, and living alone.ConclusionHealthcare usage and costs among patients treated for an NFPA are substantial and were associated with self-perceived health status, disease bother, and healthcare needs rather than endocrine status, treatment, or duration of follow-up. These findings suggest that targeted interventions addressing disease bother and unmet needs in the chronic phase are needed. Show less
Pituitary diseases are rare conditions with severe chronic multi-organ and multisystemic morbidity requiring complex multidisciplinary treatment and usually life-long drug treatment. Most cases are... Show morePituitary diseases are rare conditions with severe chronic multi-organ and multisystemic morbidity requiring complex multidisciplinary treatment and usually life-long drug treatment. Most cases are caused by functioning or non-functioning pituitary adenoma. From the patient's perspective, the burden of disease is caused by the tumour itself and associated compression symptoms, interventions, hormone excess and deficiencies, systemic manifestations of these endocrine abnormalities and general psychosocial issues that can manifest in patients with a chronic condition. In this review, patient burden is classified according to classic endocrine syndromes, with burden at diagnosis and after long-term remission, and also within the framework of value-based health care and the conceptual model of wellbeing. The recently developed patient-reported outcome measurement tool that helps to evaluate burden of patients is also discussed. (C) 2019 Elsevier Ltd. All rights reserved. Show less
Background: First-choice treatment for Cushing's disease is transsphenoidal adenomectomy. Since its introduction in the 1970s, many centers have now switched from microscopic to endoscopic surgery.... Show moreBackground: First-choice treatment for Cushing's disease is transsphenoidal adenomectomy. Since its introduction in the 1970s, many centers have now switched from microscopic to endoscopic surgery. We compared both techniques for the treatment of Cushing's disease at the Leiden University Medical Center, a European reference center for pituitary diseases.Methods: Cohort study with inclusion and follow-up of consecutive Cushing's disease patients primarily treated by transsphenoidal surgery at the Leiden University Medical Center between 1978 and 2016. We compared remission rates (primary endpoint), mortality, and complications between microscopic (performed up to 2005) and endoscopic (performed from 2003 onwards) surgery. Subgroup analyses were performed by tumor size, surgical experience, and preoperative imaging techniques. Additionally, surgeons' intraoperative findings regarding presence and removal of the adenoma were related to surgical outcome.Results: Of 137 included patients, 87 were treated microscopically and 50 endoscopically. Three months after microscopic surgery, 74 patients (86%) were in remission. Five-year recurrence-free survival was 89% (95% confidence interval [CI]: 82-96%), and ten-year recurrence free survival was 84% (95% CI: 75-93%). After endoscopic surgery, 39 patients (83%) were in remission. Both five-year and ten-year recurrence-free survival were 71% (95% CI: 55-87%). Hazard ratio for recurrence was 0.47 (95% CI: 0.19-1.14), and for mortality 2.79 (95% CI: 0.35-22.51), for microscopic versus endoscopic surgery. No learning curve was found for endoscopy, nor an influence of preoperative imaging technique for microscopy. In addition, we did not find a clear relation between the surgeons' intraoperative findings and surgical outcomes.Conclusions: This study did not identify a clear advantage of microscopic or endoscopic transsphenoidal surgery for the treatment of Cushing's disease based on clinical outcome. The transition to endoscopic surgery at our center was not accompanied by transient worsening of outcomes, which may be reassuring for those considering transitioning. Show less
Context: A somatostatin-dopamine chimera (BIM23B065) was under investigation to reduce GH secretion for the treatment of pituitary adenomas.Objective: To determine pharmacokinetics, safety, and... Show moreContext: A somatostatin-dopamine chimera (BIM23B065) was under investigation to reduce GH secretion for the treatment of pituitary adenomas.Objective: To determine pharmacokinetics, safety, and tolerability and to monitor hormonal changes after single and multiple subcutaneous BIM23B065 administrations.Design: Randomized, double-blind, placebo-controlled, parallel-group design with five single and three 13-day multiple ascending-dose cohorts.Patients: A total of 63 healthy male white volunteers were enrolled (47 active, 16 placebo).Main Outcome Measures: Pharmacokinetics, GH, prolactin (PRL), IGF-1, GH after GHRH administration, and general clinical safety criteria.Results: The maximum dosage of BIM23B065 administered in this study was 1.5 mg. BIM23B065 reduced the mean GH concentrations after 8 and 13 days of treatment. A decrease in GH release after GHRH administration indicated inhibition of the hypothalamic-pituitary-somatotropic axis. IGF-1 was not altered after single doses but showed a significant change from baseline after multiple dosing. PRL secretion was reduced in all subjects who were treated. Orthostatic hypotension and injection site reactions were commonly observed at high dosages. A 6-day uptitration period was included to successfully lower the cardiovascular effects in the multiple ascending dose part of the study.Conclusions: Proof of pharmacology of BIM23B065 was shown by a reduction in GH, IGF-1, and PRL concentrations in healthy male volunteers, supporting activity of the somatostatin analog and dopamine agonist moieties. The safety and tolerability of the higher dosing regions was limited mainly by orthostatic hypotension. Show less
PurposeNon-functioning pituitary adenomas (NFPA) have a substantial impact on patients’ healthstatus, yet research on the extent of healthcare utilization and costs among these patients isscarce.... Show morePurposeNon-functioning pituitary adenomas (NFPA) have a substantial impact on patients’ healthstatus, yet research on the extent of healthcare utilization and costs among these patients isscarce. The objective was to determine healthcare usage, associated costs, and theirdeterminants among patients treated for an NFPA.MethodsIn a cross-sectional study, 167 patients treated for an NFPA completed four validatedquestionnaires. Annual healthcare utilization and associated costs were assessed through themedical consumption questionnaire (MTA iMCQ). In addition, the Leiden Bother and NeedsQuestionnaire for pituitary patients (LBNQ-Pituitary), Short Form-36 (SF-36), and EuroQol(EQ-5D) were administered. Furthermore, age, sex, endocrine status, treatment, and durationof follow-up were extracted from the medical records. Associations were analyzed usinglogistic/linear regression.ResultsAnnual healthcare utilization included: consultation of an endocrinologist (95% of patients),neurosurgeon (14%), and/or ophthalmologist (58%). Fourteen percent of patients had ≥1hospitalization(s) and 11% ≥1 emergency room visit(s). Mean overall annual healthcare costswere € 3040 (SD 6498), highest expenditures included medication (31%), inpatient care(28%), and specialist care (17%). Factors associated with higher healthcare utilization andcosts were greater self-perceived disease bother and need for support, worse mental andphysical health status, younger age, and living alone.ConclusionHealthcare usage and costs among patients treated for an NFPA are substantial and were associated with self-perceived health status, disease bother, and healthcare needs rather thanendocrine status, treatment, or duration of follow-up. These findings suggest that targetedinterventions addressing disease bother and unmet needs in the chronic phase are needed. Show less
Lobatto, D.J.; Steffens, A.N.V.; Najafabadi, A.H.Z.; Andela, C.D.; Pereira, A.M.; Hout, W.B. van den; ... ; Furth, W.R. van 2018
PURPOSE: 'Type A' behavioural characteristics and psychosocial stress have traditionally been associated with chronic central serous chorioretinopathy (cCSC). However, a characteristical... Show morePURPOSE: 'Type A' behavioural characteristics and psychosocial stress have traditionally been associated with chronic central serous chorioretinopathy (cCSC). However, a characteristical personality profile could not be identified in these patients and the presumed association with stress is subject to controversy, due to a lack of convincing studies using validated measuring instruments. In this study, we aimed to assess maladaptive personality traits, psychological morbidity and coping strategies in patients with cCSC, in order to identify potentially modifiable psychosocial aspects which could be used in support to current standard treatment.METHODS: A cross-sectional study in a cohort of 86 patients with cCSC using validated questionnaires. Findings were compared to both Dutch population reference data and reference data from patients treated for Cushing's disease.RESULTS: Maladaptive personality traits were not more prevalent in patients with cCSC than in the general population, and psychological morbidity was not increased. Patients with cCSC were shown to make more use of passive coping, active coping and seeking social support. Interestingly, personality, psychological morbidity and coping characteristics of patients with cCSC were more comparable to features of patients treated for Cushing's disease than to population-based data.CONCLUSION: Maladaptive personality traits such as type A behavioural characteristics are not more prevalent in patients with cCSC. Patients with cCSC make more use of certain coping strategies, which could be addressed by psychosocial care to improve self-management. Further research is needed establish whether the course of disease can be improved by altering coping and reducing 'stress'. Show less
A somatostatin-dopamine chimera (BIM23B065) was under investigation to reduce growth hormone (GH) secretion for the treatment of pituitary adenomas.To determine the pharmacokinetics, safety,... Show moreA somatostatin-dopamine chimera (BIM23B065) was under investigation to reduce growth hormone (GH) secretion for the treatment of pituitary adenomas.To determine the pharmacokinetics, safety, tolerability, and to monitor hormonal changes after single and multiple subcutaneous BIM23B065 administrations.Randomized, double-blind, placebo-controlled, parallel-group design with five single and three 13-day multiple ascending dose cohorts.A total of 63 healthy male Caucasian volunteers were enrolled, 47 active, 16 placebo.Pharmacokinetics, GH, prolactin (PRL), insulin-like growth factor-1 (IGF-1), GH after GH releasing hormone (GHRH) administration, and general clinical safety criteria.The maximum dose administered of BIM23B065 in this study was 1.5 mg. BIM23B065 reduced the mean GH concentrations after 8 and 13 days of treatment. A decrease in GH release after GHRH administration indicated inhibition of the hypothalamus-pituitary-somatotropic axis. IGF-1 was not altered after single doses but showed a significant change from baseline after multiple dosing. The secretion of PRL was reduced in all treated subjects. Orthostatic hypotension and injection site reactions were commonly observed at high doses. A 6-day up-titration period was included to successfully lower the cardiovascular effects in the multiple ascending dose part of the study.Proof-of-pharmacology of BIM23B065 was shown by a reduction in GH, IGF-1 and PRL concentrations in healthy male volunteers, supportive for activity of the somatostatin analogue and dopamine agonist moieties. The safety and tolerability in the higher dosing regions was mainly limited by orthostatic hypotension.ContextObjectiveDesignPatientsMain Outcome MeasuresResultsConclusions Show less
In rare disease research, most randomized prospective clinical trials can only use limited number of patients and are comprised of highly heterogeneous populations. Therefore, it is crucial to... Show moreIn rare disease research, most randomized prospective clinical trials can only use limited number of patients and are comprised of highly heterogeneous populations. Therefore, it is crucial to report the results in such a manner that it allows for comparison of treatment effectiveness and biochemical control between studies. The aim of this review was to investigate the current methods that are being applied to measure and report growth hormone (GH) and insulin-like growth factor-1 (IGF-1) as markers for drug effectiveness in clinical acromegaly research. A systematic search of recent prospective and retrospective studies, published between 2012 and 2017, that studied the effects of somatostatin analogues or dopamine agonists in acromegaly patients was performed. The markers of interest were GH, IGF-1, and the suppression of GH after an oral glucose tolerance test (OGTT). Additionally, the use of pharmacokinetic (PK) measurements in these studies was analyzed. The sampling design, cut-off for biochemical control, reported units, and used summary statistics were summarized. A total of 49 articles were selected out of the 263 screened abstracts. IGF-1 concentrations were measured in all 49 studies, GH in 45 studies, and an OGTT was performed in 11 studies. A wide range of different cut-off values and sampling designs were used to determine biochemical control in acromegaly patients. The summary statistics were reported in various ways, with the percentage of biochemical control most frequently used. Nine studies sampled the PK at one or more time points. Non-compartmental analyses were commonly performed on the available PK data. The way GH and IGF-1 are measured and reported in acromegaly research varies considerably. A consensus on how to report study results would enable better comparisons between studies, thereby improving evidence based decision making to optimize treatment in acromegaly. OBJECTIVE SEARCH STRATEGY RESULTS CONCLUSIONS Show less
