The research presented in this thesis highlights some of the lessons learned and challenges we encountered during the transition to Value Based Health Care (VBHC)-based care for patients with a... Show moreThe research presented in this thesis highlights some of the lessons learned and challenges we encountered during the transition to Value Based Health Care (VBHC)-based care for patients with a pituitary tumor. The lack of uniform definitions across the literature currently limits comparability of outcomes between centers. By implementing a comprehensive VBHC-based set of outcomes following the three Tier model and including patient-reported outcome measures (PROMs) for endoscopic transsphenoidal pituitary surgery continuous clinical evaluations are possible and comparability between centers will be improved. We have shown that the implementation of a short-stay care trajectory is effective, feasible and can be safely done alongside a well-defined care trajectory. We also have shown, that having a pituitary tumor has a major impact on social participation, specifically having a paid job, but also healthcare use. Results presented in this thesis suggest that targeted interventions are necessary and should be based on the disease burden and needs of patients in both the acute and chronic phase of the disease. Future research should focus on obtaining international consensus to determine which outcomes should be implemented in the care trajectory for pituitary tumors. This thesis has made a first step to reaching this goal. Show less
Meulen, M. van der; Verstegen, M.J.T.; Lobatto, D.J.; Kleijwegt, M.C.; Pereira, A.M.; Biermasz, N.R.; ... ; Najafabadi, A.H.Z. 2022
Purpose: Endoscopic transsphenoidal surgery causes nasal morbidity and negatively affects health-related quality of life (HRQoL). Knowledge on actionable symptoms that could improve postoperative... Show morePurpose: Endoscopic transsphenoidal surgery causes nasal morbidity and negatively affects health-related quality of life (HRQoL). Knowledge on actionable symptoms that could improve postoperative HRQoL is therefore important. This study assessed the impact of nasal symptoms on postoperative HRQoL. Methods: This perioperative cohort study included 103 adult patients undergoing endoscopic pituitary adenoma resection (August 2016-December 2018), with measurements preoperatively, and 5 days, 6 weeks and 6 months after surgery. Nasal symptoms were measured with the Anterior Skull base nasal inventory-12, and HRQoL with the Short Form-36 (SF-36) physical (PCS) and mental component scores (MCS). Linear regression analysis was used to assess (1) determinants of postoperative nasal morbidity, (2) associations between number of symptoms or (3) individual symptoms and HRQoL, and (4) the percentage of variance of HRQoL explained by nasal symptoms. Results: The number of nasal symptoms transiently increased after surgery. No significant treatment- or disease-related determinants of nasal morbidity were identified. The number of nasal symptoms was significantly associated with a lower PCS (beta = - 1.0; 95%CI - 1.5, - 0.4), but not with MCS at 6 weeks. Similar results were observed at 6 months. Headaches (42.2%), problems with smell (42.0%), and taste (36.0%) were the most prevalent symptoms, while sense of smell and taste, and nasal discharge showed the strongest associations with HRQoL. Conclusions: Postoperative nasal symptoms, in particular problems with smell and taste, significantly affect pituitary patients' physical HRQoL. Monitoring of these symptoms may aid in determining which patients may benefit from intensified follow-up and treatment, aiming to optimize HRQoL. Show less
Context: Transsphenoidal surgery is standard care in the treatment of hormone-secreting pituitary adenomas. Current clinician-reported surgical outcome measures are one-dimensional, typically... Show moreContext: 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. Show less
Meulen, M. van der; Najafabadi, A.H.Z.; Lobatto, D.J.; Hout, W.B. van den; Andela, C.D.; Zandbergen, I.M.; ... ; Biermasz, N.R. 2020
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... Show morePurpose 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 euro1928 (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. Show less
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... Show morePurpose 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. Show less
Endoscopic transsphenoidal surgery for pituitary adenomas is a safe and highly effective first-line treatment that is well tolerated by patients. There are many potential complications, and there... Show moreEndoscopic transsphenoidal surgery for pituitary adenomas is a safe and highly effective first-line treatment that is well tolerated by patients. There are many potential complications, and there is a large variation in complexity of surgery. This article presents the philosophy, surgical techniques, and outcomes of a high-volume pituitary adenoma center. Three surgical videos illustrate some procedures. The experience has reinforced the authors' belief that experience and surgical volume are key to high quality of care. Show less
Meulen, M. van der; Najafabadi, A.Z.H.; Lobatto, D.J.; Andela, C.D.; Vlieland, T.P.M.V.; Pereira, A.M.; ... ; Biermasz, N.R. 2020
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... Show morePurpose 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. Show less
Lobatto, D.J.; Vlieland, T.P.M.V.; Hout, W.B. van den; Vries, F. de; Vries, A.F. de; Schutte, P.J.; ... ; Furth, W.R. van 2020
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.... Show moreObjective 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 euro 9992 (SD euro 4562) and historic controls euro 9818 (SD euro 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. Show less
Najafabadi, A.H.Z.; Mortel, J.P.M. van de; Lobatto, D.J.; Brandsma, D.R.; Peul, W.C.; Biermasz, N.; ... ; Furth, W.R. van 2020
Background. It has been suggested that lack of ongoing registration of patient-centered outcomes has resulted in existing care trajectories that have not been optimized for sequelae experienced by... Show moreBackground. It has been suggested that lack of ongoing registration of patient-centered outcomes has resulted in existing care trajectories that have not been optimized for sequelae experienced by meningioma patients. This study aimed to evaluate the structure of current meningioma care and identify issues and potential high-impact improvement initiatives.Methods. Using the grounded theory approach, a thematic framework was constructed based on the Dutch Comprehensive Cancer Organisation survey about issues in meningioma care trajectories. This framework was used during 3 semistructured interviews and 2 focus groups with patient-partner dyads (n = 16 participants), and 2 focus groups with health care providers (n = 11 participants) to assess issues in current meningioma care trajectories and possible solutions, including barriers to and facilitators for implementation.Results. Identified issues (n = 18 issues) were categorized into 3 themes: availability and provision of information, care and support, and screening for (neurocognitive) rehabilitation. A lack of information about the intervention and possible outcomes or complications, lack of support after treatment focusing on bodily and psychological functions, and reintegration into society were considered most important. Sixteen solutions were suggested, such as appointment of case managers (solution for 11/18 issues, 61%), assessment and treatment by physiatrists (22%), and routine use of patient-reported outcome measures for patient monitoring (17%). Barriers for these solutions were lack of budget, capacity, technology infrastructure, and qualified personnel with knowledge about issues experienced by meningioma patients.Conclusions. This study identified issues in current multidisciplinary meningioma care that are considered unmet needs by patients, partners, and health care providers and could guide innovation of care. Show less
Vries, F. de; Bruin, M.; Lobatto, D.J.; Dekkers, O.M.; Schoones, J.W.; Furth, W.R. van; ... ; Najafabadi, A.H.Z. 2020
Context: The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other... Show moreContext: The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear.Objective: The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function.Methods: Eight electronic databases were searched for articles published up to May 8, 2018. Fixed or random effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals (CI). This study is reported following the PRISMA and MOOSE guidelines.Data synthesis: 52 studies (22 low risk of bias) were included describing 18 428 subjects, consisting of patients with chronic pain (n = 21 studies) or on maintenance treatment for opioid addiction (n = 9) and healthy volunteers (n = 4). The most frequently used opioid was methadone (n = 13 studies), followed by morphine (n = 12). Prevalence of hypogonadism was 63% (95% CI: 55%-70%, 15 studies, 3250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and nondynamic testing was 15% (95% CI: 6%-28%, 5 studies, 205 patients, 57.5% males) and including only studies using the insulin tolerance tests 24% (95% CI 16%-33%, 2 studies, n = 97 patients). In 5 out of 7 studies, hyperprolactinemia was present. No clear effects on the somatotropic and hypothalamo-pituitary-thyroid axes were described.Conclusions: Hypogonadism occurs in more than half of male opioid users, and hypocortisolism in approximately one-fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable. Show less
Purpose To assess the reliability and safety of a postsurgical evaluation strategy of adrenal function using CRH stimulation and basal cortisol concentrations after transsphenoidal pituitary... Show morePurpose To assess the reliability and safety of a postsurgical evaluation strategy of adrenal function using CRH stimulation and basal cortisol concentrations after transsphenoidal pituitary surgery.Methods Retrospective cohort study of all patients undergoing endoscopic transsphenoidal surgery from 2010 to 2017, in whom early postoperative basal cortisol and/or CRH-stimulated cortisol secretion were available, including confirmation of adrenal function during follow-up. Patients with Cushing's disease were excluded. Optimal test performances were assessed using ROC analysis.Results A total of 156 patients were included. Sensitivity and specificity of the CRH test were 78% and 90%, respectively, and 86% and 92% for basal cortisol, respectively, using an optimal cutoff of 220 nmol/L. Eight patients had false-negative test results with the CRH test (normal test but adrenal insufficient at follow-up), and six patients with basal cortisol, the majority of which had multiple pituitary hormone deficiencies and fluid imbalances. No clinical adverse events occurred in patients with false-negative test results. The diagnostic performance of a single basal cortisol measurement was superior to the CRH test.Conclusions The early postoperative basal cortisol is a safe and simple measurement to guide (dis)continuation of hydrocortisone replacement. However, disturbing factors, e.g., sodium balance disorders, contraceptives, untreated hypopituitarism, and illness impact the interpretation and in those cases this measure is unreliable. We propose an algorithm in which hydrocortisone replacement at discharge is based on basal cortisol <220 nmol/L on postoperative day 2 or 3 in a stable condition. Show less
Lobatto, D.J.; Najafabadi, A.H.Z.; Vries, F. de; Andela, C.D.; Hout, W.B. van den; Pereira, A.M.; ... ; Biermasz, N.R. 2019
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
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
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
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
After treatment for a non-functioning pituitary adenoma (NFA) health-related quality of life (HR-QoL) improves considerably. However, the literature about the normalization of HR-QoL after... Show moreAfter treatment for a non-functioning pituitary adenoma (NFA) health-related quality of life (HR-QoL) improves considerably. However, the literature about the normalization of HR-QoL after treatment is inconclusive. Some researchers described a persistently decreased HR-QoL compared to reference data, while others did not. Considering this variety in observed HR-QoL outcomes, the aim of the present review was to provide a literature overview of health outcomes in patients with a NFA, using a conceptual HR-QoL model. A concrete conceptualization of the health outcomes of patients with a NFA can be helpful to understand the observed variety in HR-QoL outcomes and to improve clinical care and guidance of these patients. For this conceptualization, the Wilson and Cleary model was used. This model has a biopsychosocial character and has been validated in several patient populations. In the present review, health outcomes of patients with a NFA were described at each stage of the model e.g. biological and physiological variables, symptom status, functional status, general health perceptions and overall HR-QoL. The Wilson-Cleary model elucidates that elements at each stage of the model can contribute to the impairment in HR-QoL of patients with a NFA, which explains the reported variety in the literature. Furthermore, by applying the model, potential interventions targeting these elements can be identified. While optimal biomedical treatment has always been the focus, it is clearly not sufficient for good HR-QoL in patients with a NFA. Further improvement of HR-QoL should be supported by a pituitary specific care trajectory, including psychosocial care (e.g. self-management training), to beneficially affect characteristics of the patient and the (healthcare) environment, with the utmost goal to optimize HR-QoL in patients after treatment. Show less