Clinical features of acromegaly develop insidiously. Its diagnosis may therefore be delayed.
Our aim was to study diagnostic delay and its impact on morbidity and mortality in a nationwide cohort of ...patients with acromegaly.
Adult patients diagnosed with acromegaly between 2001 and 2013 were identified in the Swedish National Patient Registry. Diagnostic codes for predefined comorbidities associated with acromegaly were recorded between 1987 and 2013. Diagnostic delay was calculated as the time between the first registered comorbidity and the diagnosis of acromegaly.
A total of 603 patients (280 men, 323 women) with acromegaly were included. Mean (s.d.) diagnostic delay was 5.5 (6.2) years (median (minimum, maximum) 3.3 (0.0-25.9)) Diagnostic delay was 1-<5 years in 23% patients; 5-<10 years in 17%; and ≥10 years in 24%. No delay was recorded in 36% of patients. Overall, mean (s.d.) number of comorbidities was 4.1 (2.5) and was higher in patients with longer diagnostic delay (P < 0.0001). Overall, observed number of deaths was 61 (expected 42.2), resulting in a standardized mortality ratio (SMR) of 1.45 (95% CI: 1.11-1.86). Increased mortality was only found in patients with the longest diagnostic delay (1.76, 95% CI: 1.12-2.65). In the other groups, no statistically significant increase in mortality was recorded, with the numerically lowest SMR observed in patients without diagnostic delay (1.18; 95% CI: 0.68-1.92).
The diagnosis of acromegaly is delayed in most patients. Prolonged diagnostic delay is associated with increased morbidity and mortality.
Whether cancer risk in acromegaly is increased remains controversial, and the risk of benign tumors has been little studied.
To investigate the incidence of benign and malignant tumors in acromegaly ...in a nationwide population-based study.
Adult patients diagnosed with acromegaly between 1987 and 2017 were identified in the Swedish National Patient Registry. The diagnoses of benign and malignant tumors were recorded. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) for neoplasms with 95% CIs were calculated using the Swedish general population as reference.
The study included 1296 patients (52% women). Mean (SD) age at diagnosis was 51.6 (14.7) years. Median (range) follow-up time was 11.7 (0-31) years. Overall, 186 malignancies were identified in acromegalic patients compared with 144 expected in the general population (SIR 1.3; 95% CI 1.1-1.5). The incidence of colorectal and anal cancer (SIR 1.5; 95% CI 1.0-2.2), and renal and ureteral cancer (SIR 4.0; 95% CI 2.3-6.5) was increased, whereas the incidence of malignancies of the respiratory system, brain, prostate, and breast was not. Only 3 cases of thyroid cancer were recorded. Mortality due to malignancies was not increased (SMR 1.1; 95% CI 0.9-1.4). Incidence of benign tumors was increased more than 2-fold (SIR 2.4; 95% CI 2.1-2.7).
Patients with acromegaly had an increased risk of both benign and malignant tumors, including colorectal and anal cancer, and renal and ureteral cancer. Whether this is associated with acromegaly itself or due to more intensive medical surveillance remains to be shown.
•Serum PFAS levels for an exposed Swedish community are presented.•PFAS originated from AFFF result in different exposure profile.•Serum PFHxS and PFOS levels were hundredfold higher than general ...population.•Serum PFOA was higher, but to a less extent, than general population.•Shorter chain PFAS were presented in contaminated drinking water and in exposed population.
In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport.
To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined.
Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants.
The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005–2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (rs > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60.
The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure.
Purpose
Non-functioning pituitary adenomas (NFPAs) are associated with impaired well-being, increased comorbidities, and reduced long-term survival. Data on optimal management of NFPAs around ...surgical treatment are scarce, and postoperative treatment and follow-up strategies have not been evaluated in prospective trials. Here, we review the preoperative, perioperative, and early postoperative management of patients with NFPAs.
Methods
We searched Medline and the Cochrane Library for articles published in English with the following items “Pituitary neoplasms AND Surgery” and “Surgery AND Hypopituitarism”. Studies containing detailed analyses of the management of NFPAs in adult patients, including pituitary surgery, endocrine care, imaging, ophthalmologic assessment and long-term outcome were reviewed.
Results
Treatment options for NFPAs include active surveillance, surgical resection, and radiotherapy. Pituitary surgery is currently recommended as first-line treatment in patients with visual impairment due to adenomas compressing the optic nerves or chiasma. Radiotherapy is reserved for large tumor remnants or tumor recurrence following one or more surgical attempts. There is no consensus of optimal pre-, peri-, and postoperative management such as timing, frequency, and duration of endocrine, radiologic, and ophthalmologic assessments as well as management of smaller tumor remnants or tumor recurrence.
Conclusions
In clinical practice, there is a great variation in the treatment and follow-up of patients with NFPAs. We have, based on available data, suggested an optimal management strategy for patients with NFPAs in relation to pituitary surgery. Prospective trials oriented at drawing up strategies for the management of NFPAs are needed.
New therapeutic strategies have developed for the management of acromegaly over recent decades. Whether this has improved mortality has not been fully elucidated.
The primary aim was to investigate ...mortality in a nationwide unselected cohort of patients with acromegaly. Secondary analyses included time trends in mortality and treatment patterns.
A total of 1089 patients with acromegaly were identified in Swedish National Health Registries between 1987 and 2013. To analyse time trends, the cohort was divided into three periods (1987-1995, 1996-2004 and 2005-2013) based on the year of diagnosis.
Using the Swedish population as reference, standardized mortality ratios (SMRs) were calculated with 95% confidence intervals (CIs).
Overall SMR was 2.79 (95% CI: 2.43-3.15) with 232 observed and 83 expected deaths. Mortality was mainly related to circulatory diseases (SMR: 2.95, 95% CI: 2.35-3.55), including ischemic heart disease (2.00, 1.35-2.66) and cerebrovascular disease (3.99, 2.42-5.55) and malignancy (1.76, 1.27-2.26). Mortality decreased over time, with an SMR of 3.45 (2.87-4.02) and 1.86 (1.04-2.67) during the first and last time period, respectively (
= .015). During the same time periods, the frequency of pituitary surgery increased from 58% to 72% (
< 0.001) and the prevalence of hypopituitarism decreased from 41% to 23% (
< 0.001).
Excess mortality was found in this nationwide cohort of patients with acromegaly, mainly related to circulatory and malignant diseases. Although still high, mortality significantly declined over time. This could be explained by the more frequent use of pituitary surgery, decreased prevalence of hypopituitarism and the availability of new medical treatment options.
Abstract
Context
Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable.
Objective
To study overall and disease-specific mortality and predictive factors ...in an unselected nationwide cohort of patients with CD.
Design, Patients, and Methods
A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality.
Results
Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome.
Conclusion
Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
Patients with CD in remission have a more than twofold increased mortality, mainly due to cardiovascular diseases, but also due to infections and suicide.
Per- and polyfluoroalkyl substances (PFAS) are extremely persistent manmade substances. Apart from exposure through food and indoor air and dust, humans can be exposed through drinking water if the ...surface or groundwater is contaminated. In 2013 very high levels of PFOS and PFHxS were found in the drinking water from one of the two waterworks supplying the municipality of Ronneby, Sweden.
A cohort was formed, including all individuals who had lived at least one year in Ronneby during the period 1980–2013 (ñ63,000). Each year, addresses that got their drinking water from the contaminated water works were identified. Through the Swedish personal identity number, each individual was linked to registers providing diagnoses and prescriptions for hyper- and hypothyroidism.
In total, 16,150 individuals had ever been exposed. The hazard ratios did not indicate any excess risk of hyperthyroidism among those with contaminated water. For hypothyroidism, the risk of being prescribed medication was significantly increased among women with exposure during the mid part of the study period (but not men). However, the association with period of exposure was non-monotonic, so the significance is considered to be a chance finding. Our research was limited by the relatively simple exposure assessment.
•High serum PFOS and PFHxS from fire fighting foam drinking water contamination.•Thyroid disease in the general population studied 1985 to 2013.•Linkage to national patient and prescription registers.•No association between PFAS in drinking water and hyperthyroidism.•Increased risk of hypothyroidism medication in one sub-group probably due to chance.
Pituitary adenomas and their consequences impact mortality and morbidity. We studied the healthcare costs, survival, and cost-effectiveness of growth hormone (GH) vs no GH replacement in patients ...with non-functioning pituitary adenoma (NFPA).
A cohort study including all NFPA patients followed from 1987 or the date of diagnosis until the time of death or December 31, 2019, in the Västra Götaland region, Sweden. Data to assess resource use, costs, survival, and cost-effectiveness were collected from patient records and regional/national healthcare registries.
A total of 426 patients with NFPA (274 men) with a follow-up of 13.6 ± 6.8 years (mean ± SD) were included. The total annual healthcare cost was higher in patients receiving GH (€9287) than those without GH (€6770), mainly driven by a higher pharmaceutical cost. Glucocorticoid replacement therapy (P = .02), diabetes insipidus (P = .04), body mass index (BMI) (P < .01), and hypertension (P < .01) were all individually associated with a higher total annual cost. The survival rate was higher in the GH group (HR hazard ratio 0.60; P = .01) and reduced in patients with glucocorticoid replacement (HR 2.02; P < .01) or diabetes insipidus (HR 1.67; P = .04). The cost per gained life-year for GH vs no GH replacement was about €37 000.
This healthcare utilization study identified several factors driving the cost of care in NFPA patients, such as GH replacement, adrenal insufficiency, and diabetes insipidus. Life expectancy was increased in those with GH replacement and reduced in patients with adrenal insufficiency and diabetes insipidus.
Context:
Craniopharyngiomas (CPs) in adults have been associated with excess mortality.
Objective:
The aim of the study was to investigate mortality and morbidity in patients with childhood-onset and ...adult-onset CP.
Methods:
Patients with CP were identified and followed in Swedish national health registries, 1987 through 2011. The inclusion criteria for the CP diagnosis were internally validated against patient records in 28% of the study population.
Settings:
This was a nationwide population-based study.
Patients:
A total of 307 patients (151 men and 156 women) were identified and included (mean follow-up, 9 years; range, 0–25 years). The inclusion criteria had a positive predictive value of 97% and a sensitivity of 92%.
Intervention:
There were no interventions.
Main Outcome Measures:
Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) with 95% confidence intervals were calculated using the Swedish population as the reference.
Results:
During the study, 54 patients died compared with the expected number of 14.1, resulting in an SMR of 3.2 (2.2–4.7) for men and 4.9 (3.2–7.2) for women. Patients with childhood-onset (n = 106) and adult-onset (n = 201) CP had SMRs of 17 (6.3–37) and 3.5 (2.6–4.6), respectively. Patients with hypopituitarism (n = 250), diabetes insipidus (n = 110), and neither of these (n = 54) had SMRs of 4.3 (3.1–5.8), 6.1 (3.5–9.7), and 2.7 (1.4–4.6), respectively. The SMR due to cerebrovascular diseases was 5.1 (1.7–12). SIRs were 5.6 (3.8–8.0) for type 2 diabetes mellitus, 7.1 (5.0–9.9) for cerebral infarction, 0.7 (0.2–1.7) for myocardial infarction, 2.1 (1.4–3.0) for fracture, and 5.9 (3.4–9.4) for severe infection. The SIR for all malignant tumors was 1.3 (0.8–2.1).
Conclusions:
This first nationwide population-based study of patients with CP demonstrated excess mortality that was especially marked in patients with childhood-onset disease and among women. Death due to cerebrovascular diseases was increased 5-fold. Hypopituitarism and diabetes insipidus were negative prognostic factors for mortality and morbidity. Patients with CP had increased disease burden related to type 2 diabetes mellitus, cerebral infarction, fracture, and severe infection.
Background
Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide ...cohort of patients with presumed CD in Sweden.
Methods
Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.
Results
Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (
P
< 0.05).
Conclusion
The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
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