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 (1991Denmark ( -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.

Objective Growth hormone (GH) nadir (GHnadir) during oral glucose tolerance test (OGTT) is an important tool in diagnosing acromegaly, but data evaluating the need to adjust cut-offs to biological variables utilizing today's assay methods are scarce. We therefore investigated large cohorts of healthy subjects of both sexes to define normal GHnadir concentrations for a modern, sensitive, 22 kD-GH-specific assay. Design Multicenter study with prospective and retrospective cohorts (525 healthy adults: 405 females and 120 males). Methods GH concentrations were measured by the IDS-iSYS immunoassay after oral application of 75 g glucose. Results GHnadir concentrations (µg/L) were significantly higher in lean and normal weight subjects (group A) compared to overweight and obese subjects (group B); (males (M): A vs B, mean: 0.124 vs 0.065, P = 0.0317; premenopausal females without estradiol-containing OC (OC-EE) (FPRE): A vs B, mean: 0.179 vs 0.092, P < 0.0001; postmenopausal women (FPOST): A vs B, mean: 0.173 vs 0.078, P < 0.0061). Age, glucose metabolism and menstrual cycle had no impact on GHnadir. However, premenopausal females on OC-EE (FPREOC) exhibited significantly higher GHnadir compared to all other groups (all P < 0.0001). BMI had no impact on GHnadir in FPREOC (A vs B, mean: 0.624 vs 0.274, P = 0.1228). Conclusions BMI, sex and OC-EE intake are the major determinants for the GHnadir during OGTT in healthy adults. Using a modern sensitive GH assay, GHnadir concentrations in healthy subjects are distinctly lower than cut-offs used in previous guidelines for diagnosis and monitoring of acromegaly.

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.

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(1) Discordant values in terms of high GH levels are prevalent in SA patients and more so if applying glucose-suppressed GH; (2) targeting discordant levels of either GH or IGF-I translates into SA dose increase and improved biochemical control; (3) even though QoL was not improved in this study, we suggest biochemical assessment of disease activity to include glucose-suppressed GH also in SA patients.

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 associated with an increased risk of falls in both groups. The incidence rate ratios (IRR) of fall-related injuries as hip, pelvis/lower-back and skull/facial fractures were higher in people with T2D than controls [IRR 1.08 (CI:95%:1.02-1.15), IRR 1.21 (CI:95%: 1.12-1.48) and IRR 1.11 (CI:95%:1.02-1.21)]. Conclusion: People with diabetes have an increased risk of first fall and a higher incidence of fall-related injuries including fractures. Advanced aging and sex are non-modifiable risk factors, whereas diabetes, the use of SSRIs and opioids and alcohol abuse could be potentially modifiable risk factors for falls. Gaining information on risk factors for falls could guide the management of diabetes treatment i.e. choice of drugs, which enables us to improve treatment particularly in people with a high risk of falls and fractures associated with high mortality.

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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, CI95%:1.26-1.62) and also during the 5-year pre-diagnostic period (HR:1.15, CI95%:1.03-1.28). More individuals with acromegaly received social security benefit compared to 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, CI95%:0.50-0.95) as was parenthood (HR:0.56, CI95%:0.39-0.80), whereas neither educational level (HR:0.61, CI95%:0.35-1.06) nor separation (HR:1.13, CI95%:0.86-1.47) were different. Female gender and insufficient disease control were associated with a significantly worse socioeconomic status. Conclusion 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.