Acromegaly Quality Of Life Questionnaire Research Articles

THU070 Randomized, Placebo-controlled Phase 3 Trial Protocol Assessing The Efficacy And Safety Of Octreotide Subcutaneous Depot (CAM2029) In Patients With Acromegaly

Abstract Disclosure: D. Ferone: Advisory Board Member; Self; Recordati, Novartis-AAA, Sandoz, Camurus. Grant Recipient; Self; Bristol-Myers Squibb, Novartis-AAA, Ipsen, Camurus. Research Investigator; Self; Camurus. P. Freda: Research Investigator; Self; Camurus. L. Katznelson: Advisory Board Member; Self; Recordati, Camurus, Amryt. Research Investigator; Self; Camurus. F. Gatto: Research Investigator; Self; Camurus. A. Gilis-Januszewska: Research Investigator; Self; Camurus. M.B. Gordon: Advisory Board Member; Self; Camurus, Crinetics, HRA Pharma, Novo Nordisk, Recordati. Grant Recipient; Self; Amryt, Ascendis, Camurus, Corcept, Crinetics, Ipsen, Novartis Pharmaceuticals, Novo Nordisk, Opko, Pfizer, Inc., Strongbridge. Research Investigator; Self; Camurus. P. Kadioglu: Research Investigator; Self; Camurus. P. Maffei: Research Investigator; Self; Camurus. J.R. Seufert: Research Investigator; Self; Camurus. J. Silverstein: Advisory Board Member; Self; Amryt, Recordati. Research Investigator; Self; Camurus. J.L. Spencer-Segal: Grant Recipient; Self; Camurus. Research Investigator; Self; Camurus. M. Harrie: Employee; Self; Camurus. A. Svedberg: Employee; Self; Camurus. F. Tiberg: Employee; Self; Camurus. Extended-release formulations of the somatostatin analogues (SSAs), octreotide and lanreotide, are first-line medical therapies for patients with acromegaly who have contraindications for, or are not cured by, surgical intervention and/or radiotherapy. Treatment goals, regardless of modality, include biochemical normalization of insulin-like growth factor 1 (IGF-1) and growth hormone (GH), symptom relief, tumor control, and maintenance of pituitary function. From the patient perspective, treatment satisfaction, autonomy, and quality of life may be as important as biochemical control. Constraints of current SSA formulations include incomplete biochemical and symptom control, and a lack of convenient self-administration options. Octreotide subcutaneous (SC) depot (CAM2029) is a novel FluidCrystal® formulation of octreotide designed for easy administration by patients, in a ready-to-use prefilled syringe or injection pen. In previous clinical trials, CAM2029 provided more than five-fold higher bioavailability compared to the currently marketed long-acting octreotide formulation.The efficacy and safety of CAM2029 in acromegaly is being evaluated in a 6-month, randomized, double-blind, placebo-controlled phase 3 trial (NCT04076462). 72 patients were randomized 2:1 to monthly SC doses of CAM2029 20 mg or placebo, with the option for self-administration. Key inclusion criteria included a biochemical and clinical diagnosis of acromegaly due to a pituitary adenoma with persistent or recurrent disease, treatment with a stable dose of octreotide long-acting release or lanreotide Autogel for at least 3 months as monotherapy, and controlled disease with IGF-1 ≤1 x upper limit of normal (ULN). Key exclusion criteria included GH ≥2.5 μg/L at screening, pituitary surgery within 6 months of screening, prior pituitary irradiation, and recent treatment with pasireotide, pegvisomant, or dopamine agonists. The primary endpoint is the proportion of patients with normalized IGF-1 (≤1 x ULN) after 6 months of treatment. Other endpoints include change from baseline of IGF-1, GH and patient-reported outcomes (Treatment Satisfaction Questionnaire for Medication, Self-Injection Assessment Questionnaire, Acromegaly Quality of Life Questionnaire, EQ-5D-5L), safety and tolerability, clinical signs and symptoms of acromegaly, use of rescue medication and octreotide pharmacokinetics. The estimated primary completion date for the trial is May 2023. After completing study treatment, patients may switch to open-label treatment in a phase 3 long-term safety and extension trial of CAM2029 (NCT04125836). Presentation: Thursday, June 15, 2023

Psychiatric disorders and anger in patients with controlled acromegaly.

Acromegaly (ACRO) is a chronic rare disease caused by a pathological increase in growth hormone (GH) secretion. In ACRO an increased prevalence of psychiatric disorders has been demonstrated, in particular depressive disorders, associated to a significant deterioration of the quality of life, independently from disease control. In addition, anger feelings, often detected in subjects affected by chronic disease, have not yet been investigated, in pituitary patients. Aim of the study was to evaluate in ACRO patients with a controlled disease, compared to patients suffering for non-functioning pituitary adenoma (NFPA) 1) prevalence of depressive and anxiety disorders, and 2) expression and control of anger feelings. The second purpose was to evaluate the correlation between psychiatric disorders, anger feelings and the "activity of disease," that is active ACRO that needs medical treatment versus cured ACRO. This is a cross-sectional, observational study, which included 53 patients enrolled at the Neuroendocrinology Outpatient Clinic of "Città della Salute e della Scienza di Torino". Of the 53 enrolled patients (24 male and 29 female), 34 had ACRO, while 19 had NFPA, as control group. All subjects went through the following self-administered, validated psychological tools: SF-36 (Short-Form 36 Item); STAXI - 2; BDI-II (Beck Depression Inventory -II); STAI (State-Trait Anxiety Inventory). Only in ACRO group, patients completed PASQ (Patient-Assessed Acromegaly Symptom Questionnaire) and ACROQoL (Acromegaly Quality of Life Questionnaire) questionnaires. In addition 45 patients underwent the International Neuropsychiatric Short Interview to assess the presence of a psychiatric disorder. For each patient, anthropometric, clinical and biochemical information was collected. A higher frequency of psychiatric anxiety and mood disorders (not reported in the medical history) was observed in patients with controlled ACRO. In the SF-36 questionnaire, a lower score was found in the "emotional well-being" items in ACRO compared to NFPA, particularly in those with cured ACRO. Cured acromegalic patients had a worse score in "emotional well-being," "energy/fatigue" and "general health" items. Finally, subjects in ACRO group obtained a lower score in the ability to control anger and a higher score in the physical expression of it, demonstrating a tendency to more aggressive behaviors. This study showed that psychiatric illness is often hidden in patient suffering from ACRO, despite normal IGF-I levels. Recovery from the disease do not necessarily improve QoL scores, in fact in cured patients the quality of life can be even worse.

Association between pain, arthropathy and health-related quality of life in patients suffering from acromegaly. A cross-sectional study

Despite successful therapy, acromegalic patients have reduced health-related quality of life (HRQoL) compared to healthy controls. Finding predictors of poor HRQoL can be crucial to improving these patients' global health state. Aim: The primary objective of the study was to find out predictors of HRQoL. Secondary objectives were: (I) to determine correlations with AcroQoL subscales, and (II) to identify predictors for subscales. In this cross-sectional study conducted in 2019 at the Messina Policlinic Hospital, 45 acromegalic patients were assessed at the Physical and Rehabilitative Medicine Ambulatory. During routine outpatient clinic attendances, the following questionnaires were administered: Acromegaly Quality of Life Questionnaire (AcroQoL), Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC). We furthermore included the following variables obtained by medical record review: age, BMI, disease duration, previous surgery (Yes/No), previous radiotherapy (Yes/No), use of GH lowering medications (Yes/No), hypertension (Yes/No), diabetes mellitus (Yes/No), and biochemical control of the disease (Yes/No): immunoradiometric assays were employed to serum GH and IGF-1 measurements to identify biochemical control of the disease. Correlation between outcome measures and AcroQoL has been performed. Pearson's r was calculated for continuous data following normal distribution (AcroQoL, PASQ, AcroQoL-B, AcroQoL-R, WOMAC-P), while Spearman's rank order correlation was calculated for non-normally distributed data (WOMAC, WOMAC-F, WOMAC-S, AcroQoL-P) and point-biserial correlation for binary variables (biochemically controlled disease, use of GH lowering medications, radiotherapy, surgery). The same correlation analysis was performed for the AcroQoL subscales. Multiple linear regression with backwards, stepwise analysis was used to assess the influence on AcroQoL of correlated variables. AcroQoL was strongly negatively correlated with PASQ (r=-0.700, p<0.001) and negatively correlated with WOMAC [rs (43)=-0.530, p<0.001] and among WOMAC subscales with WOMAC-Physical fitness [rs (43)=-0.518, p<0.001] WOMAC-Pain [r (43)=-0.428, p=0.003], WOMAC-Stiffness [rs (43)=-0.393, p=0.007], and radiotherapy [r (43) =-0.314, p=0.035]. After univariate stepwise regression, PASQ was the strongest independent predictor of AcroQoL, with R2 of 0.392 [F (1,43)=27.695, p<0.001]. This study shows that the severity of painful symptoms is the most important predictor of HRQoL in patients with acromegaly; at the same time, acromegalic arthropathy leads to pain and to a variable amount of functional impairment, exerting great impact on the patient's perception of his health status. Measure of the progression of arthropathy and symptomatic management could lead to a great HRQoL benefit.

Quality of life of patients with acromegaly: comparison of different therapeutic modalities

ABSTRACT Background Acromegaly is a rare disease that significantly affects patients’ quality of life (QoL) – especially appearance, pain, depression, energy and vitality. The aim is to assess and compare the acromegaly patients’ QoL related to the type of pharmacotherapy using specific and generic QoL measuring instruments. Research design and methods A cross-sectional questionnaire-based study among 163 hospitalized acromegaly patients was conducted. QoL was measured by Acromegaly Quality of Life Questionnaire (AcroQol), Short-Form Health Survey (SF-36) and EQ-5D-3 L. Results Women had lower AcroQol values than men 50 vs. 66 (p < 0.05). Lower values for octreotide than octreotide + pegvisomant were found with all questionnaires: 57 vs. 67 AcroQol (p = 0.0405), 0.699 vs. 0.7586 EQ-5D (p = 0.0595) and 57.94 vs. 66.06 SF-36 scores (p > 0.093) . A significant correlation between AcroQoL, SF-36 and EQ-5D-3 L scores (rs> 0, р < 0.00001) was revealed. AcroQol, EQ-5D and SF-36 are reliable questionnaires applicable for Bulgarian population with acromegaly. Conclusion This pilot study confirmed that combination therapy which includes biological therapy is related to higher physical appearance AcroQol scores than nonbiological monotherapy – a conclusion which should be further confirmed.

The clinical complexity of patients with acromegaly

ObjectivesThe main aim of the study was to investigate the factors related to the biopsychosocial complexity in the group of patients with acromegaly with different disease activity. MethodsA cross-sectional observational study was performed. First, a linguistic adaptation of the INTERMED – self-assessment questionnaire (IMSA) and after that the assessment of the biopsychosocial complexity among patients with acromegaly and the factors which relate to the complexity was made. The following tools were used to assess: biopsychosocial complexity: The INTERMED –self-assessment (IMSA); quality of life: The World Health Organization Quality of Life – BREF (WHOQoL) and Acromegaly Quality of Life questionnaire (AcroQol); mental state: The General Health Questionnaire – 28 (GHQ-28). ResultsThe final analysis included 71 patients. According to the principal component analysis the mental state (GHQ-28) and the quality of life (AcroQol) are the most important factors related to the clinical complexity among patients with acromegaly. In the model created by a stepwise regression analysis for the total IMSA score higher growth hormone (GH) concentration, longer illness duration, and better general quality of life were included as the protective factors of the clinical complexity. By contrast, a high score in the severe depression subscale of GHQ-28 was a factor of higher clinical complexity. ConclusionThe mental state and quality of life are the most important determinants of the clinical complexity in the group of patients with acromegaly whereas the biochemical normalization is of lesser importance.

Quality of life after long-term biochemical control of acromegaly.

To assess long-term quality of life (QoL) in patients with sustained biochemical control of acromegaly, comparing those receiving vs not receiving pharmacotherapy (primary analysis); to assess change in QoL over time (secondary analysis). Cross-sectional study, with a secondary longitudinal component, of 58 patients with biochemically controlled acromegaly. All had participated in studies assessing QoL years previously, after having undergone surgery ± radiotherapy. One cohort received medical therapy [MED (n = 33)]; the other did not [NO-MED (n = 25)]. QoL was assessed by the 36-Item-Short-Form Health Survey (SF-36), Acromegaly Quality of Life Questionnaire (AcroQoL), Gastrointestinal Quality of Life Index (GIQLI), Symptom Questionnaire, and QoL-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). Mean (± SD) duration of biochemical control was 15.0 ± 6.4years for MED and 20.4 ± 8.2years for NO-MED (p = 0.007). 58% of subjects scored < 25% of normal on ≥ 1 SF-36 domain and 32% scored < 25% of normal on ≥ 4 of 8 domains. Comparing MED vs NO-MED and controlling for duration of biochemical control, there were no significant differences in QoL by SF-36, AcroQOL, GIQLI, Symptom Questionnaire, or QoL-AGHDA. Growth hormone deficiency (GHD) but not radiotherapy predicted poorer QoL. In MED, QoL improved over time in three AcroQoL domains and two GIQLI domains. In NO-MED, QoL worsened in two SF-36 domains and two Symptom Questionnaire domains; QoL-AGHDA scores also worsened in subjects with GHD. A history of acromegaly and development of GHD, but not pharmacologic or radiotherapy, are detrimental to QoL, which remains poor over the long-term despite biochemical control.

Clinical Applicability of Patient- and Clinician-Reported Outcome Tools in the Management of Patients With Acromegaly

ObjectiveWe aimed to assess treatment outcomes and disease control status in patients with acromegaly using patient- and clinician-reported outcome tools and to analyze correlations among different components of both tools. MethodsThis cross-sectional study included 72 patients from a national referral center with a median follow-up of 8 (5-12) years. The baseline SAGIT score at diagnosis was determined retrospectively, whereas the follow-up SAGIT and acromegaly quality of life questionnaire (AcroQoL) results were assessed at the most recent visit and by additional telephone interviews. ResultsAll SAGIT subscores decreased significantly from baseline to follow-up (global score from 14 to 4 [P < .001]). The SAGIT scores at baseline did not discriminate the current disease control status. However, a higher baseline SAGIT score and subscore T were associated with uncontrolled disease after the first-line treatment. Diagnostic delay was correlated with baseline S, A, G, and global SAGIT scores. At the follow-up, the global SAGIT score discriminated between cured/controlled and uncontrolled groups (4 vs 6 [P = .007]). The AcroQoL score was 69.3, with the personal relations subscale being the least affected and the physical scale being the most affected. There was no difference in the AcroQoL score between patients classified as uncontrolled or cured/controlled. At baseline and follow-up, there were significant negative correlations between S and A subscores and AcroQoL score. A higher body mass index, the presence of swelling, joint symptoms, headaches, sleep apnea, and hypertension significantly impaired quality of life. ConclusionOur results emphasize the complementary nature of the patient- and clinician-reported outcome tools in acromegaly management. We identified modifiable signs, symptoms, and comorbidities as treatment targets that might help clinicians improve quality of life in this population.

Validation of Acromegaly Quality of Life Questionnaire (AcroQoL) for the Iranian population

BackgroundAcromegaly is a chronic disease significantly affects the physical, emotional, and health-related aspects of patients' life. This study aimed to validate the Acromegaly Quality of Life Questionnaire (AcroQoL) for the Persian-speaking population.MethodsThis cross-sectional study recruited 73 Iranian patients with a confirmed diagnosis of acromegaly. The content validity of the scales was evaluated by an expert panel of eight endocrinologists applying content validity index (CVI) and content validity ratio (CVR). Construct validity was assessed by using confirmatory factor analysis. Internal consistency was assessed on the basis of Cronbach’s alpha, and a goodness-of-fit (GoF) index was calculated to display whether the model fitted the data.ResultsCVI and CVR yielded values of 0.85 and 0.80, respectively (Acceptable CVI: > 0.78 and CVR: > 0.75). The average variances extracted (AVE) from physical and psychological dimensions were 0.520 and 0.462, respectively, exceeding the minimum criterion of 0.40. Cronbach’s alpha for physical and psychological dimensions equaled 0.868 and 0.866, respectively, indicating the adequate internal consistency of multiple items for each construct. The subscales’ R square and path coefficient were greater than the recommended threshold as 0.75 (physical dimension: 0.778, psychological dimension: 0.873), demonstrating the suitability of this criterion. Finally, the GoF value of 0.29 indicated the model's moderate fit.ConclusionsThe findings revealed that the Persian version of AcroQoL is of adequate validity and reliability for evaluating the quality of life of Iranian people with acromegaly.

Patient-reported outcomes in patients with acromegaly treated with pegvisomant in the ACROSTUDY extension: A real-world experience

To report the effects of pegvisomant (PEGV) treatment on patient-reported outcomes in acromegaly patients. We conducted an extension study of an open-label, multinational, non-interventional study (ACROSTUDY) evaluating the long-term safety and efficacy of PEGV for acromegaly in routine clinical practice. Enrolled patients were rollover patients from ACROSTUDY, or treatment naïve/semi-naïve (NSN; no PEGV within 6 months of enrollment). Exploratory efficacy endpoints were changes in symptoms with the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) and quality of life with the Acromegaly Quality of Life questionnaire (AcroQoL) analyzed by controlled or uncontrolled IGF-I levels. Results were analyzed in all patients, in NSN patient subgroup, and by diabetes status. A total of 544 patients with acromegaly were enrolled, including 434 rollover subjects from ACROSTUDY and 110 NSN patients. Mean PEGV treatment duration was 7.8 years (range, 0-19.6 years). Overall, the majority of PASQ scores improved over time, but there was no significant difference between IGF-I controlled or uncontrolled groups. In the NSN subgroup, most PASQ and AcroQoL scores remained similar to baseline up to 1 year, regardless of IGF-I control. Patients with diabetes reported better PASQ scores over time with PEGV treatment, regardless of IGF-I control. IGF-I normalization increased from 10% of patients at baseline to more than 78% at year 10, with a mean daily PEGV dose of 18.7mg. Overall, patients treated with PEGV had small improvements in PASQ. While IGF-I normalization increased with PEGV treatment, IGF-I control had no effects on PASQ and AcroQoL scores.

Quality of life in patients with acromegaly receiving lanreotide autogel: a real-world observational study.

Patients with acromegaly have substantially reduced quality of life (QoL). This study evaluated QoL in patients with acromegaly treated with lanreotide autogel. This was a prospective, non-interventional, observational, multi-centre study conducted in Poland (NCT02396966). We included patients with acromegaly, who received treatment with lanreotide autogel 120mg for ≥ 3 months and < 3 years. Patients were assessed approximately every 4-5months for twoyears (six visits). QoL was measured with the Acromegaly Quality of Life Questionnaire (AcroQoL). Of 152 patients enrolled from November 2014 to May 2018 in 37 centres, 24 were excluded due to major protocol deviations. The results are reported for the study population (n = 128). At baseline, the median [95% confidence interval (CI)] time from diagnosis was 3.3 (2.8, 4.2)years, and the median time since lanreotide initiation was 13.4 (9.9, 17.3) months. Symptoms of acromegaly were present at baseline in 86% of patients (headache, 57%; sweating, 58%; joint symptoms, 64%); symptoms remained unchanged at two years in 82% of patients. At baseline, 27% of patients had hormonal control (growth hormone < 2.5 μg/L and insulin-like growth factor-1 within the normal range); hormonal control status did not change during the study period in over 81% of patients. At baseline, 88% of patients were either very satisfied or satisfied with treatment; treatment satisfaction was unchanged in 62% of patients over the study period. Mean (95% CI) AcroQoL scores at baseline were as follows: total, 50.3 (47.3, 53.3); physical dimension, 48.8 (45.2, 52.4); psychological dimension, 51.3 (48.2, 54.4); appearance subdimension, 40.7 (37.5, 43.8); and personal relations subdimension, 62.5 (58.8, 66.2). The psychological appearance subscore improved by 3.8 points (1.2, 6.5) over the two years; scores in the remaining dimensions and subdimensions did not change substantially. The total AcroQoL score remained unchanged over the twoyears, regardless of prior acromegaly treatment, surgery or radiotherapy, hormonal control, or lanreotide dosing interval. No new safety findings were identified. AcroQoL total scores and physical and psychological subscores remained stable but impaired among patients with long-lasting acromegaly treated with lanreotide autogel for two years. The psychological appearance subdimension improved numerically.

Mapping of the acromegaly quality of life questionnaire to ED-5D-5L index score among patients with acromegaly.

This study aimed to develop a mapping function that links the acromegaly quality of life (AcroQoL) questionnaire to EQ-5D-5L to obtain a preference-based utility value to inform economic evaluation. A nationwide cross-sectional questionnaire survey among patients with acromegaly was conducted online in China during 17 December 2019 to 6 January 2020. The study sample was randomly divided into a training set and a validation set. Ordinary least squares (OLS), Tobit, beta-based mixture, and adjusted limited dependent variable mixture models were tested for development of the function in the training set. Total and subscale scores and individual items of AcroQoL were included as predictors in the models along with their squared terms and demographic and clinical characteristics, and selected by backward stepwise selection. The root mean square error, mean absolute error, Akaike's information criterion, Bayesian information criterion and adjusted R-square were used to assess goodness of fit and predictive ability of the models. There were 424 adult patients with acromegaly eligible for this analysis. Average EQ-5D-5L index score and AcroQoL score for them was 0.82 (SD = 0.15) and 44.3 (SD = 22.9), respectively. A total of 60 candidate models were tested. Considering model simplicity and predictive ability in both training and validation set, the best model was the OLS model using scores of physical dimension and its square term as predictors. A validated mapping function was developed in this study for estimating EQ-5D scores using AcroQoL outcomes. Its external validity can be further tested in other population with Acromegaly.

Surgically treated acromegaly patients have a similar quality of life whether controlled by surgery or requiring additional medical therapy (QuaLAT Study)

PurposeThere is no consensus on quality of life (QOL) in patients with acromegaly requiring medical treatment after surgery compared with those achieving remission by surgery alone.MethodsQuaLAT is a cross-sectional study comparing QOL in surgery-only treated acromegaly patients versus those requiring medical treatment post-surgery. Patients attending clinics were identified and divided into—Group 1: patients who had surgery only and were in biochemical remission, Group 2: all patients on medical treatment post-surgery, Group 3: patients from Group 2 with biochemical control. Participants were asked to fill three questionnaires; Acromegaly Quality of Life Questionnaire (ACROQOL), 36-Item Short Form Survey (SF36), and Fatigue Severity Scale (FSS).ResultsThere were 32 patients in Group 1 and 25 in Group 2. There was no difference in QOL scores between groups 1 and 2, as measured by ACROQOL (mean difference [MD] = − 2.5, 95% CI − 16.6 to 11.6; p = 0.72), SF36v2 [Physical component score (PCS) MD = − 4.9, 95% CI − 10.9 to 1.2; p = 0.12; mental component score MD = − 3.0, 95% CI − 10.5 to 4.4; p = 0.44], or FSS (MD = − 0.004, 95% CI − 1.14 to 1.33; p = 0.1). Comparison between groups 1 and 3 however showed that PCS (and 3 subdomains) was significantly better in group 3 (MD = − 8.3, 95% CI − 14.8 to -1.8; p = 0.01). All three QOL scores were lower when compared with healthy controls.ConclusionsMedical treatment not only achieves a QOL comparable to surgery, it may also be associated with better QOL in physical subdomains. When compared with healthy controls, QOL remains worse in treated acromegaly patients compared to controls.

Changes in Quality of Life After Long-Term Biochemical Control of Acromegaly

Acromegaly results in impaired quality of life (QoL), which improves but does not normalize after biochemical control of growth hormone (GH) excess. There are few data regarding long-term QoL in patients with sustained biochemical control of acromegaly. We hypothesized that QoL would continue to improve over time but remain poor. We studied 2 cohorts with biochemically controlled (normal IGF-1 level) acromegaly. MED (n=42) underwent surgery but required somatostatin analog (n=30) or GH receptor antagonist monotherapy (n=12); n=16 had undergone radiation. SURG (n=24) were in remission after surgery ± radiation (n=10). GH stimulation testing was performed in all SURG; n=11 had GH deficiency (GHD). QoL was assessed at 2 timepoints by the 36-Item-Short-Form Health Survey (SF-36) (MED, SURG), Acromegaly Quality of Life Questionnaire (AcroQoL) (MED), Gastrointestinal Quality of Life Index (GIQLI) (MED), Symptom Questionnaire (SQ) (SURG), and QoL-Assessment of GHD in Adults (AGHDA) (SURG). Time between timepoints 1 and 2 was 5.4 ± 1.0 vs 13.6 ± 1.2 years (MED vs SURG, p<0.001), and mean duration of biochemical control for MED vs SURG at timepoint 2 was 14.8 ± 6.6 vs 20.8 ± 8.2 years (p<0.001). At timepoint 2, mean (± SD) age (61 ± 12 years), mean BMI (30 ± 7 kg/m2), sex (68% female), and hypopituitarism (64% with ≥1 pituitary hormone deficiency) were similar between MED and SURG; mean IGF-1 index (IGF-1 level/mean normal range) was 1.00 ± 0.37 for MED vs 0.78 ± 0.40 for SURG (p=0.08); 79% of MED remained on medication. In MED, there was no change in SF-36 scores between timepoints, but all AcroQoL subscales and 2 GIQLI domains (Physical State, Emotions) improved, even after controlling for age, BMI, radiation treatment, and hypopituitarism. Results were similar in the 79% who remained on medication at timepoint 2. In SURG, QoL scores worsened on the SF-36 Pain domain and Physical Health Summary Score and SQ Depression and Somatic subscales (p≤0.01) but did not remain significant after controlling for age, BMI, radiation treatment, GHD, and adrenal insufficiency. After controlling for those variables, QoL by AGHDA worsened (p=0.02). At timepoint 2, % scoring in the lowest quartile (<25%) of normal for age on the SF-36 was similar between MED and SURG: 57% scored <25% of normal on ≥1 SF-36 domain and 29% scored <25% of normal on ≥4 of 8 domains. GHD in SURG was associated with poorer SF-36 scores at timepoint 2 (6 domains and Mental Health Summary Score; p<0.05). Radiation treatment did not predict poorer SF-36 scores. In conclusion, an average of 15 to 20 years after biochemical control of acromegaly by surgery ± radiation ± pharmacologic treatment, QoL remained low in many patients. QoL was poorer in patients with GHD than without but overall did not differ between those on and off pharmacologic therapy. Our data suggest that a history of acromegaly and development of GHD, but not medical treatment, are detrimental to QoL.

Medical Treatment Achieves Similar Quality of Life to Surgically Treated Acromegaly Patients in Remission: The QuaLAT Study

Background: Quality of life (QOL) in acromegaly has been a subject of interest in several published studies; however, there is no consensus on how QOL in patients who require medical treatment after surgery compares with those who achieve remission by surgery only. Aim: Quality of life after acromegaly treatment (QuaLAT) is a case-control questionnaire-based study with the aim to compare the QOL in those who were treated with surgery only with those who required medical treatment after surgery at a single tertiary centre for acromegaly. Methods: Patients with acromegaly attending endocrinology clinics were identified via our database. These were matched on the duration of disease into those who underwent surgery and went into disease remission biochemically (Group 1), and those who did not achieve biochemical remission after surgery and therefore required further medical treatment to control the disease (Group 2). Participants were then asked to fill three questionnaires to measure their QOL; Acromegaly Quality of Life Questionnaire (ACROQOL), and two generic questionnaires; 36-Item Short Form Survey (SF36) v2, and Fatigue Severity Scale (FSS). Results: 20 patients from each group participated in the study. The mean±SD duration of acromegaly (years) was similar in the two groups (9.8±6.9 vs 9.7±6.9 p=0.653). The majority of patients in the medical group were on somatostatin analogues, either alone or in combination (n=14), with four and two patients on cabergoline and pegvisomant alone respectively. There was no difference in QOL scores between groups 1 & 2, as measured by ACROQOL (mean score±SD 54.4±24.8 vs 55.3±26.1 p=0.765), SF36v2 (Physical component score 40.1± 11.1 vs 45.6±12.0 p=0.235; mental component score 41.7±13.0 vs 43.1±16.4 p=0.601), or FSS (mean score±SD 4.4±2.2 vs 4.5±2.0 p=0.985) questionnaires. There was no difference in ages between both groups and there were 75% females in group 1 and 45% in group 2. When compared with healthy controls as reported in the published literature, all three QOL scores were lower in our cohort [1-3]. Conclusions: Medical treatment achieves similar QOL to surgically treated acromegaly patients in remission in the long term. When compared with healthy controls, QOL remains worse in treated acromegaly patients.

Improved AcroQoL scores in acromegaly after sagittal split ramus osteotomy with Le Fort I osteotomy.

SummaryAcromegaly is associated with a low quality of life (QoL), which is partially attributable to appearance. However, appearance changes are only partially reversible with treatments of growth hormone excess. This case study describes a 41-year-old Japanese man who presented with mandibular prognathism. Acromegaly was suspected because of the patient’s facial features. Subsequent examination revealed a pituitary tumour with elevated levels of growth hormone and insulin-like growth factor 1 (IGF1), confirming a diagnosis of acromegaly. We assessed his QoL with the acromegaly QoL questionnaire (AcroQoL) before transsphenoidal surgery, and all AcroQoL scores were low. Although the pituitary adenoma was resected, his serum IGF1 levels started to increase again and MRI identified a residual pituitary lesion. After lanreotide and pegvisomant injection therapies improved his serum IGF1 levels, we reassessed his AcroQoL scores, however, the results showed worsening scores regarding appearance and personal relationships, and the patient expressed interest in surgery for mandibular prognathism. We performed sagittal split ramus osteotomy (SSRO) with Le Fort I osteotomy, thus, the patient’s AcroQoL scores improved. This case shows that SSRO with Le Fort I osteotomy for mandibular prognathism, rather than control of serum IGF1 level alone, improved the patient’s AcroQoL score, especially for both psychological well-being and approval of appearance. Acromegaly has many complications, including its negative impact on patients’ perception of their appearance and patients’ QoL can be improved using multiple options, in addition to controlling growth hormone levels.Learning pointsThe patient’s AcroQoL scores worsened despite biochemical normalization of IGF-1 levels.Mandibular prognathism due to acromegaly can be successfully operated by performing sagittal split ramus osteotomy with Le Fort I osteotomy.Frequent monitoring of AcroQoL scores and appropriate response to negative results can improve the overall QoL.

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

BackgroundWhereas biochemical response is often used as a primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for patients to consider treatment successful. We performed a systematic review and meta-analysis to assess the effect of treatment on symptoms and HRQoL in acromegaly.MethodsSeven electronic databases were searched for longitudinal studies assessing patient-reported symptoms or HRQoL in acromegaly. Meta-analyses were performed to assess differences during treatment for the Acromegaly Quality of Life Questionnaire (AcroQoL) and Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and standardized mean difference (SMD) for individual symptoms (interpretation: 0.2 small, 0.5 moderate, and 0.8 large effect). Treatment-naive and previously treated patients were assessed separately.ResultsForty-six studies with 3301 patients were included; 24 contributed to quantitative analyses. Thirty-six studies used medication as main treatment, 1 transsphenoidal adenomectomy, and 9 various treatments. Symptoms and HRQoL both improved: AcroQoL increased 2.9 points (95% CI, 0.5 to 5.3 points), PASQ decreased –2.3 points (95% CI, –1.3 to –3.3 points), and individual symptom scores decreased for paresthesia –0.9 (95% CI, –0.6 to –1.2), hyperhidrosis –0.4 (95% CI, –0.1 to –0.6), fatigue –0.3 (95% CI, –0.1 to –0.6), arthralgia –0.3 (95% CI, –0.1 to –0.5), headache –0.3 (95% CI, 0.0 to –0.6), and soft-tissue swelling –0.2 (95% CI, 0.0 to –0.4).ConclusionSymptoms and HRQoL improved during acromegaly treatment. Consensus is needed on which symptoms should be included in a potential core outcome set, taking into account symptom frequency, severity, and sensitivity to change, which can be used in clinical practice and as outcome in trials.

Vertebral Fractures Associated with Spinal Sagittal Imbalance and Quality of Life in Acromegaly: A Radiographic Study with EOS 2D/3D Technology

Introduction: Acromegaly is commonly complicated by arthropathy and skeletal fragility with high risk of vertebral fractures (VFs). Objective: This study aimed to assess whether VFs may be associated with sagittal spine deformities, arthropathy, impaired quality of life (QoL), pain, and disability. Methods: Thirty-eight patients with acromegaly (median age: 55 years, 20 males) and 38 matched control subjects were evaluated by a low-dose sagittal and coronal planes, X-ray imaging system (EOS®-2D/3D) for morphometric VFs, radiological signs of spine arthropathy, and spine deformities (Cobb thoracic index ≥40°, pelvic incidence minus lumbar lordosis ≥10°, pelvic tilt >20°, and sagittal vertical axis ≥4 cm) determining sagittal spine imbalance. Acromegalic patients were also evaluated by questionnaires for QoL (Acromegaly QoL Questionnaire [AcroQoL] and Short Form-36 [SF-36]) and pain and disability (Western Ontario and McMaster University [WOMAC]). Results: Acromegalic patients showed higher prevalence of thoracic hyperkyphosis (i.e., Cobb thoracic index ≥40°; p = 0.04) and pelvic tilt >20° (p = 0.02) than control subjects. VFs were found in 34.2% of acromegalic patients (p = 0.003 vs. control subjects), in relationship with higher prevalence of hyperkyphosis (p = 0.03), pelvic tilt >20° (p = 0.04), sagittal vertical axis ≥4 cm (p = 0.03), and moderate/severe subchondral degeneration (p = 0.01). Moreover, patients with VFs had lower AcroQoL general health (p = 0.007) and SF-36 general health (p = 0.002) scores and higher WOMAC pain (p = 0.003) and global (p = 0.009) scores than patients who did not fracture. Conclusions: In acromegaly, VFs may be associated with spine deformities and sagittal imbalance, spine arthropathy, impaired QoL, and disability.

Sleep disorders and cognitive dysfunction in acromegaly.

In the general population, sleep disorders are associated with an increased risk of cognitive impairment. The prevalence of sleep disorders, such as sleep apnea, in acromegalic patients is higher than in the general population, and they may have additional risk of cognitive impairment due to acromegaly treatment and comorbidities. We aim to study the relationship between sleep disturbances and cognitive dysfunction in a group of acromegalic patients. We studied 67 consecutive acromegalic patients. We performed a neurocognitive assessment and patients completed the Acromegaly Quality of Life Questionnaire (AcroQoL), Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index. Of the 67 acromegaly patients in the study, 38.8% were male and median age at the neurological examination was 56 (IQR 48, 65). Approximately 6-10% of patients had impaired cognitive assessment, depending on the test. In linear regression models adjusted for age, sex, BMI, disease duration, and disease activity, poorer sleep quality was associated with lower global cognitive z-score (B = -0.03, 95% CI -0.06, -0.002). Daytime somnolence was associated with poorer physical AcroQoL sub-score (B = -0.04, 95% CI -0.08, -0.002). Sleep quality was associated with poorer overall AcroQoL (B = -0.03, 95% CI -0.05, -0.006), physical AcroQoL (B = -0.04, 95% CI -0.07, -0.005), psychological AcroQoL (B = -0.02, 95% CI -0.04, -0.001), and social AcroQoL (B = -0.02, 95% CI -0.04, -0.0009). In acromegaly patients, we found robust evidence that poor sleep quality is associated with poorer quality of life, and some evidence that it is associated with poorer cognitive function.

Correlations of clinical parameters with quality of life in patients with acromegaly: Taiwan Acromegaly Registry

The objectives of this study were to evaluate the associations between clinical parameters and quality of life (QOL) of patients with acromegaly in Taiwan and to identify the impacts of hormone control, regimens, or co-morbidities on acromegalic patients' daily life. From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. Clinical data were recorded. The QOL of enrolled patients were assessed by using Acromegaly Quality of Life Questionnaire (AcroQoL). This study enrolled 272 acromegalic subjects (117 males, 155 females). Remission, defined by normalization of IGF-1, had significant positive association with QOL scores in psychological/appearance (PSY/APP) dimension (β=6.760, p=0.023). Somatostatin analogues therapy had negative associations with total score and score in psychological (PSY) dimension (β=-4.720, p=0.046 and β=-5.388, p=0.035, respectively). Diabetes mellitus had negative associations with score in PSY dimension and psychological/personal relations (PSY/PER) dimensions (β=-5.839, p=0.034 and β=-7.516, p=0.013, respectively). Cerebral vascular accident (CVA) had significant negative associations with total score and scores in physical (PHY), PSY, and PSY/PER dimensions (β=-26.632, p=0.013; β=-28.353, p=0.024; β=-25.648, p=0.026; and β=-34.586, p=0.006, respectively). All these associations remained significant even after adjusted with sex and age. Our analysis suggested that not only hormone control but also therapeutic regimens and presence of co-morbidities might affect QOL of patients with acromegaly in some dimensions.

SUN-LB080 ACROSTUDY - Safety and Efficacy of a Cohort of 110 Naïve Patients with Acromegaly Treated with Pegvisomant

Background: ACROSTUDY is an open-label, non-interventional post-authorization safety study that began in 2004 to evaluate safety in at least 1000 acromegaly patients treated with the GH receptor antagonist pegvisomant (PEGV). This commitment was fulfilled in Jan 2013. ACROSTUDY was later amended to enroll an additional 110 patients that were naïve/semi-naive to PEGV treatment. Semi-naïve patients are defined as not having received PEGV therapy for at least 6 months prior to enrollment. Objectives: The primary objectives were to: 1) assess the long-term safety of PEGV in real world practice; 2) assess the effect of IGF-I normalization on treatment outcomes, including safety, glucose control and patient-reported outcomes (PROs). Patients & Methods: 110 patients with Acromegaly 53.6% male, 81.8% Caucasian, median age 42.4 years at diagnosis; median age 48.9 years at PEGV start. Patients were considered ‘IGF-I Controlled’ if the most temporally-related IGF-I measurement was normal for that laboratory. Safety data including adverse events and liver tests were collected. IGF-I and HbA1C were measured; PROs were evaluated using the Acromegaly Quality of Life Questionnaire (AcroQoL) and PatientAssessed Acromegaly Symptom Questionnaire (PASQ), stratified by IGF-I control. Results: No new safety signals were identified in this sub-study. IGF-I SDS >2 decreased from 87% of patients at baseline to 31% at year 2 at a mean dose(±SD) of 10.4(±7.45) mg/day; patients with IGF-I SDS <2 had a mean dose of 14.8(±6.7). Among IGF-I controlled patients, median (range) HbA1C levels were 5.8% (5.4-6.1) at baseline and 5.6% (4.5-7.2) at year 2; in IGF-I uncontrolled patients, HbA1C was 6.1% (4.9-6.6) at baseline and 6.3% (2.9-10.6) at year 2. Among IGF-I controlled patients, median (range) global AcroQoL scores were 54.6 (24-73) at baseline and 61.4 (13-86) at year 2; while in IGF-I uncontrolled patients, median global AcroQoL score was 59.7 (8-92) at baseline and 63.6 (25-76) at year 2. Among IGF-I controlled patients, median (range) total PASQ score was 20 (3-38) at baseline and 17.5 (1-40) at year 2; in IGF-I uncontrolled patients, median total PASQ score was 17 (0-44) at baseline and 14 (3-39) at year 2. A greater number of the six individual symptoms of the PASQ score showed a positive trend for improvement from baseline to year 2 in the IGF-I controlled patients than in the uncontrolled patients. Summary: In this real-life world international study, overall biochemical control (i.e. normal IGF-I) was achieved with pegvisomant in 64.3% patients by year 2. Improved IGF-I control was associated with improved HbA1C, QoL and symptoms of acromegaly. One limitation of the study was that the PEGV dose may not have been adequately titrated to achieve IGF-I normalization. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.