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Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

Objective: Active acromegaly is subject to sex differences in growth hormone (GH) and Insulin like growth factor 1 (IGF-I) patterns as well as clinical features but whether this also pertains to controlled disease is unclear. Design: In a cross-sectional, multi-centre study, 84 patients with acromegaly (F = 43, M = 41), who were considered controlled after surgery alone (n = 23) or during continued somatostatin receptor ligand (SRL) treatment (n = 61), were examined. Methods: Serum concentrations of GH, insulin, glucose and free fatty acid (FFA) were measured during an oral glucose tolerance test (OGTT) together with baseline serum IGF-I and completion of two HR-Qol questionnaires (acromegaly quality of life questionnaire [AcroQol] and Patient-assessed Acromegaly Symptom Questionnaire [PASQ]). Results: The mean age at the time of the study was 57 (±1.1) years and the majority of females (were postmenopausal. Females had significantly higher fasting GH but comparable IGF-I standard deviation scores (SDS). Using fasting GH < 1.0 µg/L as cut off, disease control was less prevalent in females (F: 56% vs. M: 83%, p =.007) whereas a comparable figure was observed using IGF-I SDS < 2 (F:79% vs. M:76%, p =.71). Compared with males, female patients showed impaired AcroQol physical score (p =.05), higher fasting FFA (p =.03) and insulin concentrations during the OGTT (p =.04). Conclusion: In patients with acromegaly considered controlled, postmenopausal females exhibited higher GH levels than males despite comparable IGF-I levels, which also translated into impaired metabolic health and well-being. Our findings point to the relevance of including GH measurements in the assessment of disease control and suggest that disease-specific sex differences prevail after treatment.

UNLABELLED: New evidence points toward that impaired postural control judged by center of pressure measures during quiet stance is a predictor of falls in people with type 1 and type 2 diabetes-even in occurrence of well-known risk factors for falls.INTRODUCTION/AIM: People with type 1 diabetes (T1D) and type 2 diabetes (T2D) are at risk of falling, but the association with impaired postural control is unclear. Therefore, the aim was to investigate postural control by measuring the center of pressure (CoP) during quiet standing and to estimate the prevalence ratio (PR) of falls and the fear of falling among people with diabetes compared to controls.METHODS: In a cross-sectional study, participants with T1D (n = 111) and T2D (n = 106) and controls without diabetes (n = 328) were included. Study procedures consisted of handgrip strength (HGS), vibration perception threshold (VPT), orthostatism, visual acuity, and postural control during quiet stance measured by CoPArea (degree of body sway) and CoPVelocity (speed of the body sway) with "eyes open," "eyes closed" in combination with executive function tasks. A history of previous falls and fear of falling was collected by a questionnaire. CoPArea and CoPVelocity measurements were analyzed by using a multiple linear regression model. The PR of falls and the fear of falling were estimated by a Poisson regression model. Age, sex, BMI, previous falls, alcohol use, drug, HGS, VPT, orthostatism, episodes of hypoglycemia, and visual acuity were covariates in multiple adjusted analyses.RESULTS: Significantly larger mean CoPArea measures were observed for participants with T1D (p = 0.022) and T2D (0.002), whereas mean CoPVelocity measures were only increased in participants with T2D (p = 0.027) vs. controls. Additionally, T1D and T2D participants had higher PRs for falls (p = 0.044, p = 0.014) and fear of falling (p = 0.006, p < 0.001) in the crude analyses, but the PRs reduced significantly when adju

INTRODUCTION: People with diabetes could have an increased risk of falls as they show more complications, morbidity and use of medication compared to the general population. This study aimed to estimate the risk of falls and to identify risk factors associated with falls in people with diabetes. The second aim was to estimate fall-related injuries including lesions and fractures including their anatomic localization in people with diabetes compared with the general population. Methods: From the Danish National Patient Register we identified people with Type 1 Diabetes (T1D) (n=12,896), Type 2 Diabetes (T2D) (n=407,009). The cohort was divided into two groups with respective control groups matched on age and sex (1:1). All episodes of people hospitalized with a first fall from 1996 to 2017 were analyzed using a Cox proportional-hazards model. Risk factors such as age, sex, diabetic complications, a history of alcohol abuse and the use of medication were included in an adjusted analysis. The incidence rate and rate ratio of falls and the anatomic localization of fall-related injuries as lesions and fractures were identified. Results and Discussion: The cumulative incidence, of falls requiring hospital treatment, was 13.3% in T1D, 11.9% in T2D. In the adjusted analysis T1D and T2D were associated with a higher risk of falls [T1D, Hazard Ratio (HR): 1.33 (95% CI: 1.25 - 1.43), T2D, HR: 1.19 (95% CI:1.16 - 1.22), respectively]. Women [group 1, HR 1.21 (CI:95%:1.13 - 1.29), group 2, HR 1.61 (CI:95%:1.58-1.64)], aged >65 years [groups 1, HR 1.52 (CI:95%:1.39 - 1.61), group 2, HR 1.32 (CI:95%:1.58-1.64)], use of selective serotonin receptor inhibitors (SSRI) [group 1, HR 1.35 (CI:95%:1.1.30 - 1.40), group 2, HR 1.32 (CI:95%:1.27-1.38)], opioids [group 1, HR 1.15 (CI:95%:1.12 - 1.19), group 2, HR 1.09 (CI:95%:1.05-1.12)] and a history of alcohol abuse [group 1, HR 1.77 (CI:95%:1.17 - 2.15), group 2, HR 1.88 (CI:95%:1.65-2.15)] were significantly ass

Objective: Data on sex differences in acromegaly at the time of diagnosis vary considerably between studies. Design: A nationwide cohort study including all incident cases of acromegaly (1978–2010, n = 596) and a meta-analysis on sex differences in active acromegaly (40 studies) were performed. Method: Sex-dependent differences in prevalence, age at diagnosis, diagnostic delay, pituitary adenoma size, insulin-like growth factor 1 (IGF-I) and growth hormone (GH) concentrations were estimated. Results: The cohort study identified a balanced gender distribution (49.6% females) and a comparable age (years) at diagnosis (48.2 CI95% 46.5–49.8 (males) vs. 47.2 CI95% 45.5–48.9 (females), p = 0.4). The incidence rate significantly increased during the study period (R2 = 0.42, p < 0.01) and the gender ratio (F/M) changed from female predominance to an even ratio (SR: 1.4 vs. 0.9, p = 0.03). IGF-ISDS was significantly lower in females compared to males, whereas neither nadir GH nor pituitary adenoma size differed between males and females. In the meta-analysis, the weighted percentage female was 53.3% (CI95% 51.5–55.2) with considerable heterogeneity (I2 = 85%) among the studies. The mean age difference at diagnosis between genders was 3.1 years (CI95% 1.9–4.4), and the diagnostic delay was longer in females by 0.9 years (CI95% −0.4 to 2.1). Serum IGF-I levels were significantly lower in female patients, whereas nadir GH, and pituitary adenoma size were comparable. Conclusion: There are only a minor sex differences in the epidemiology of acromegaly at the time of diagnosis except that female patients are slightly older and exhibit lower IGF-I concentrations and a longer diagnostic delay.

CONTEXT: Acromegaly is usually a sporadic disease, but familial cases occur. Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with familial pituitary adenoma predisposition. However, the pathogenicity of some AIP variants remains unclear and additional unknown genes may be involved.OBJECTIVE: To explore the phenotype and genotype of a large kindred carrying the p.R304Q AIP variant.METHODS: The family comprised 52 family members at risk of carrying the p.R304Q AIP variant including a case with gigantism and one with acromegaly and several family members with acromegalic features. Nine family members (three trios) underwent exome sequencing to identify putative pathogenic variants.RESULTS: We identified 31 p.R304Q carriers, and based on two cases with somatotropinomas, the disease penetrance was 6%. We observed physical signs of acromegaly in several family members, which were independent of AIP status. Serum insulin-like growth factor-I (IGF-I) levels in all family members were above the mean for age and sex (IGF-I SDS: +0.6 [CI95% +0.4-0.9], P < .01). Exome analysis identified two candidate genes: PDE11A, known to be associated with the development of adrenal tumours, and ALG14. Ten asymptomatic p.R304Q family members (age >50 years) were screened for the PDE11A and ALG14 variant; both variants were present in five of ten persons.CONCLUSIONS: This large family adds new information on the p.R304Q AIP variant, and data suggest two new candidate genes could be associated with growth hormone excess.

CONTEXT: Acromegaly is an insidious disease associated with severe somatic morbidity but data on socioeconomic status are scarce.OBJECTIVE: To study the socioeconomic status in acromegaly in a population-based follow-up study.METHODS: All incident cases of acromegaly (n = 576) during the period 1977-2010 were included. For every patient, 100 persons were sampled from the general population matched for date of birth and gender (comparison cohort). Cox regression and hazard ratios (HR), conditional logistic regression and linear regression with 95% confidence intervals (CI) were used.OUTCOME MEASURES: Retirement, social security benefit, annual income, cohabitation, separation, parenthood and educational level.RESULTS: The proportion of retired individuals was significantly higher in patients with acromegaly after the time of diagnosis (HR, 1.43; 95% CI, 1.26-1.62) and also during the 5-year pre-diagnostic period (HR, 1.15; 95% CI, 1.03-1.28). More individuals with acromegaly received social security benefit compared with the comparison cohort during the initial period after the time of diagnosis. Among patients who maintained a job, the annual income was similar to the comparison cohort. Compared with the background population, cohabitation was lower (HR, 0.69; 95% CI, 0.50-0.95) as was parenthood (HR, 0.56; 95% CI, 0.39-0.80), whereas neither educational level (HR, 0.61; 95% CI, 0.35-1.06) nor separation (HR, 1.13; 95% CI, 0.86-1.47) were different. Female gender and insufficient disease control were associated with a significantly worse socioeconomic status.CONCLUSIONS: 1) Socioeconomic status is impaired in patients with acromegaly even before a diagnosis of acromegaly. 2) Females and patients without disease remission have worse outcomes. 3) Early diagnosis and effective treatment of acromegaly could be important factors in mitigating the negative impact on socioeconomic factors.

Design Valid data on acromegaly incidence, complications and mortality are scarce. The Danish Health Care System enables nationwide studies with complete follow-up and linkage among health-related databases to assess acromegaly incidence, prevalence, complications and mortality in a population-based cohort study. Method All incident cases of acromegaly in Denmark (1991–2010) were identified from health registries and validated by chart review. We estimated the annual incidence rate of acromegaly per 106 person-years (py) with 95% confidence intervals (95% CIs). For every patient, 10 persons were sampled from the general population as a comparison cohort. Cox regression and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used. Results Mean age at diagnosis (48.7 years (CI: 95%: 47.2–50.1)) and annual incidence rate (3.8 cases/106 persons (95% CI: 3.6–4.1)) among the 405 cases remained stable. The prevalence in 2010 was 85 cases/106 persons. The patients were at increased risk of diabetes mellitus (HR: 4.0 (95% CI: 2.7–5.8)), heart failure (HR: 2.5 (95% CI: 1.4–4.5)), venous thromboembolism (HR: 2.3 (95% CI: 1.1–5.0)), sleep apnoea (HR: 11.7 (95% CI: 7.0–19.4)) and arthropathy (HR: 2.1 (95% CI: 1.6–2.6)). The complication risk was also increased before the diagnosis of acromegaly. Overall mortality risk was elevated (HR: 1.3 (95% CI: 1.0–1.7)) but uninfluenced by treatment modality. Conclusion (i) The incidence rate and age at diagnosis of acromegaly have been stable over decades, and the prevalence is higher than previously reported. (ii) The risk of complications is very high even before the diagnosis. (iii) Mortality risk remains elevated but uninfluenced by mode of treatment., DESIGN: Valid data on acromegaly incidence, complications and mortality are scarce. The Danish Health Care System enables nationwide studies with complete follow-up and linkage among health-related databases to assess acromegaly incidence, prevalence, complications and mortality in a population-based cohort study.METHOD: All incident cases of acromegaly in Denmark (1991-2010) were identified from health registries and validated by chart review. We estimated the annual incidence rate of acromegaly per 10(6) person-years (py) with 95% confidence intervals (95% CIs). For every patient, 10 persons were sampled from the general population as a comparison cohort. Cox regression and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used.RESULTS: Mean age at diagnosis (48.7 years (CI: 95%: 47.2-50.1)) and annual incidence rate (3.8 cases/10(6) persons (95% CI: 3.6-4.1)) among the 405 cases remained stable. The prevalence in 2010 was 85 cases/10(6) persons. The patients were at increased risk of diabetes mellitus (HR: 4.0 (95% CI: 2.7-5.8)), heart failure (HR: 2.5 (95% CI: 1.4-4.5)), venous thromboembolism (HR: 2.3 (95% CI: 1.1-5.0)), sleep apnoea (HR: 11.7 (95% CI: 7.0-19.4)) and arthropathy (HR: 2.1 (95% CI: 1.6-2.6)). The complication risk was also increased before the diagnosis of acromegaly. Overall mortality risk was elevated (HR: 1.3 (95% CI: 1.0-1.7)) but uninfluenced by treatment modality.CONCLUSION: (i) The incidence rate and age at diagnosis of acromegaly have been stable over decades, and the prevalence is higher than previously reported. (ii) The risk of complications is very high even before the diagnosis. (iii) Mortality risk remains elevated but uninfluenced by mode of treatment.