Acromegaly management in the Nordic countries: A Delphi consensus survey.

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.

Thyroid function test variability and cardiovascular morbidity in hyperthyroidism.

OBJECTIVE: The variability of thyroid function tests (TFTs) during antithyroid drug (ATD) therapy and its association with adverse health outcomes have not been previously studied. The aim of this study was to evaluate the association of TFT variability and cardiovascular morbidity during ATD therapy. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Hyperthyroid patients (n = 394) treated with ATD therapy at Tampere University Hospital between March 2016 and December 2018 were followed up for a median time of 1.5 years (interquartile range 0.8-2.0). The coefficients of variation (CVs) of the follow-up thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) measurements were determined. The associations of TFT variability and baseline clinical factors with cardiovascular disease (CVD) -associated hospital visits were assessed with logistic regression analyses. RESULTS: In the multivariable analyses, age (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.03-1.09), male gender (OR: 2.33, 95% CI: 1.03-5.28) and fT4-CV (OR: 1.02, 95% CI: 1.01-1.04) were independent risk factors for cardiovascular morbidity, whereas baseline positive thyrotropin receptor antibodies (TRAbs) were associated with lower cardiovascular morbidity (OR: 0.29, 95% CI: 0.14-0.61). When the patients with baseline TRAb positivity were studied separately, fT4-CV was associated with cardiovascular morbidity (OR: 1.03, 95% CI: 1.00-1.05). CONCLUSIONS: During ATD therapy, fT4 variability is associated with an increased cardiovascular morbidity. Although positive TRAbs are associated with a lower cardiovascular morbidity compared with hyperthyroidism with negative autoantibodies, the variability of fT4 is associated with cardiovascular morbidity also in patients with positive TRAbs.

Immunohistochemical Glucagon-like Peptide-1 Receptor Expression in Human Insulinomas.

Insulinomas are rare functional pancreatic neuroendocrine tumours, which metastasize in 10% of cases. As predicting the prognosis can be challenging, there is a need for the determination of clinicopathological factors associated with metastatic potential. The aim of this study is to evaluate the glucagon-like peptide-1 receptor (GLP-1R) expression in insulinomas and to analyse its association with clinicopathological features and patient outcome. This retrospective study involves pancreatic tumour tissue samples from fifty-two insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with a monoclonal GLP-1R antibody. Forty-eight of the forty-nine (98%) non-metastatic tumours expressed GLP-1R, while one non-metastatic, multiple endocrine neoplasia type 1 (MEN1)-related tumour and all three of the metastatic tumours lacked GLP-1R expression. The lack of GLP-1R expression was associated with impaired overall survival, larger tumour diameter, higher Ki-67 PI and weaker insulin staining. Somatostatin receptor 1-5 expression did not differ between GLP-1R-positive and GLP-1R-negative insulinomas. In conclusion, the lack of GLP-1R expression is associated with metastatic disease and impaired survival in insulinoma patients. Thus, GLP-1R expression could be a useful biomarker in estimating the metastatic potential of the tumour and the prognosis of surgically treated patients.

Long-term health-related quality of life in persons diagnosed with an insulinoma in Finland 1980-2010.

OBJECTIVE: Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long-term effects on health and the quality of life, we studied the long-term health-related quality of life (HRQoL) in insulinoma patients. DESIGN, PATIENTS AND MEASUREMENTS: The HRQoL of adults diagnosed with an insulinoma in Finland in 1980-2010 was studied with the 15D instrument, and the results were compared to those of an age- and gender-matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as ±0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long-term HRQoL. RESULTS: Thirty-eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 ± 0.072 vs 0.903 ± 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL. CONCLUSIONS: In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.

Long-term cardiovascular morbidity and mortality in patients treated for differentiated thyroid cancer.

OBJECTIVES: Thyroid hormone suppression therapy has been widely used in the treatment of thyroid cancer, but concerns have been raised about the cardiovascular risks of this treatment. The objective of this study was to evaluate long-term cardiovascular morbidity and mortality in patients treated for differentiated thyroid cancer (DTC) and to assess the effect of TSH suppression and radioiodine (RAI) treatment on the cardiovascular outcome. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Patients (n = 901) treated for DTC between 1981 and 2002 at 2 Finnish University hospitals were compared with a randomly chosen reference group (n = 4485) matched for age, gender and the place of residence. Kaplan-Meier and Cox regression analyses were used to estimate the risk of morbidity or death due to different cardiovascular diseases (CVD) after the diagnosis of DTC. RESULTS: Morbidity due to any CVD (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.05-1.28) and due to all arrhythmias (HR 1.25, CI 1.06-1.48) and atrial fibrillation (AF) (HR 1.29, CI 1.06-1.57) was more frequent in the DTC patients than in the controls. The increased cardiovascular morbidity was confined to patients with a mean TSH level below 0.1 mU/L (HR 1.27, CI 1.03-1.58) and to those treated with RAI (HR 1.18, CI 1.05-1.31). Cardiovascular mortality, however, was lower among the patients than the controls (HR 0.73, CI 0.58-0.92), due to a lower mortality from coronary artery disease. CONCLUSIONS: Differentiated thyroid cancer patients have an increased CVD morbidity, which is mostly accountable to AF and to TSH suppression below 0.1 mU/L.

An integrative systematic review of interprofessional education on diabetes.

Interprofessional education (IPE) aims at enhancing the ability of healthcare professionals from different disciplines to work together effectively, improving the quality of patient care. An interprofessional approach is essential in diabetes management, but there is only limited evidence of the effects of diabetes-specific IPE. The aim of this integrative review is to gather all relevant recent data on the outcomes of IPE on diabetes management. The search in the CINAHL, Medline and PsycINFO databases resulted in 1136 potential studies. An inductive content analysis was used to synthesize the key findings of the 14 studies found to fulfill the inclusion criteria of the systematic review. Two main categories and four subcategories of findings were identified. Firstly, the achieved outcomes included individual gain (e.g., learner´s confidence and motivation to treat patients with diabetes) and external benefits (e.g., benefits for the patient). Secondly, the experiences of IPE included both challenges (e.g., competing interests of different professions) and strengths (e.g., practical approach to diabetes management). In conclusion, the findings indicate that both learners and patients with diabetes benefit from IPE on diabetes management. Educators are encouraged to adopt practical IP approaches in diabetes education. However, it is necessary to estimate the resources available. More research is needed on the cost-effectiveness, long-term effects, and patient perspective of IPE on diabetes management.

[Insulinomas in Tampere University Hospital Special Responsibility Area in 1980-2010]. / Insulinoomat Tampereen yliopistollisen sairaalan erityisvastuualueella 1980-2010.

BACKGROUND: Insulin-producing neuroendocrine tumours (iNETs) are rare, but their incidence is increasing. We studied the incidence, clinical picture, diagnostics, and treatment of insulinomas diagnosed in 1980 to 2010. METHODS: Retrospective analysis of insulinomas diagnosed in Tampere University Hospital. RESULTS: We found 23 iNET cases corresponding to an incidence of 0.7/million/year. All had neuroglycopenic symptoms and 83% had autonomic ones. The median diagnostic delay (from first symptoms up to diagnosis) was 25 months. Preoperative imaging found the tumor in 87%. Twenty-one out of 22 patients who underwent surgery recovered completely. CONCLUSIONS: Despite improved imaging the diagnostic delay of iNETs remained unchanged. Hypoglycemia and insulinoma should be considered as a cause of unspecific, symptomatic attacks.

Cardiovascular morbidity and mortality in surgically treated hyperthyroidism - a nation-wide cohort study with a long-term follow-up.

OBJECTIVE: Previous studies suggest that patients with hyperthyroidism remain at an increased risk of cardiovascular morbidity even after restoring euthyroidism. The mechanisms of the increased risk and its dependency on the different treatment modalities of hyperthyroidism remain unclear. The aim of this long-term follow-up study was to compare the rate of hospitalizations for cardiovascular causes and the mortality in hyperthyroid patients treated surgically with an age- and gender-matched reference population. PATIENTS AND MEASUREMENTS: A population-based cohort study was conducted among 4334 hyperthyroid patients (median age 46 years) treated with thyroidectomy in 1986-2007 in Finland and among 12,991 reference subjects. Firstly, the hospitalizations due to cardiovascular diseases (CVD) were analysed until thyroidectomy. Secondly, the hazard ratios for any new hospitalization due to CVDs after the thyroidectomy were calculated in Cox regression analysis adjusted with the prevalent CVDs at the time of thyroidectomy. RESULTS: The risk of hospitalization due to all CVDs started to increase already 5 years before the thyroidectomy, and by the time of the operation, it was 50% higher in the hyperthyroid patients compared to the controls (P < 0·001). After the thyroidectomy, the hospitalizations due to all CVDs (HR 1·15), hypertension (HR 1·23), heart failure (HR 1·17) and valvular diseases or cardiomyopathies (HR 1·55) remained more frequent among the patients than among the controls for 20 years after thyroidectomy. The increased morbidity was not clearly related to the aetiology of hyperthyroidism. Despite the increased CVD morbidity among the patients, there was no difference in cardiovascular mortality. CONCLUSIONS: The present study shows that hyperthyroidism increases the risk of hospitalization due to CVDs and the risk is sustained up to two decades after effective surgical treatment. However, there was no excess CVD mortality in the middle-aged patient cohort studied.

Haemodynamics of hyperthyroidism: increased cardiac work and findings related to vasodilatation.

OBJECTIVE: Hyperthyroidism increases cardiovascular morbidity and mortality, but the underlying mechanisms are not fully understood. In this study we compared non-invasive haemodynamics between 20 hyperthyroid patients and 60 euthyroid subjects. METHODS: The measurements were performed median 6 days after the initiation of antithyroid medication when the patients were still hyperthyroid. Three controls matched for age, sex, body mass index, and smoking status were selected for each patient. Recordings were performed during rest and passive head-up tilt using whole-body impedance cardiography, radial pulse wave analysis, and finger blood pressure measurements. RESULTS: Systolic and diastolic blood pressures in the aorta and radial artery were similar in hyperthyroid and euthyroid subjects, while finger blood pressure was 16/12 mmHg lower in hyperthyroidism (p<0.001). Pulse wave velocity and aortic pulse pressure were similar, but radial pulse pressure was ~5 mmHg higher in hyperthyroidism (p=0.040) due to augmented amplification (p=0.045). Systemic vascular resistance was reduced (-18%), whereas heart rate (+19 beats/min), cardiac index (+28%), and left cardiac work (+31%) were increased in hyperthyroidism (p<0.001). Subendocardial viability ratio, reflecting the balance between coronary perfusion and pressure load, was reduced by 19% in hyperthyroidism (p<0.001). Compared with euthyroid subjects, hyperthyroid patients presented with reductions in systolic and diastolic finger blood pressures (p<0.001), and higher increase in heart rate (p=0.014) during upright posture. CONCLUSIONS: Hyperthyroid patients exhibited hyperdynamic circulation, reduced vascular resistance, reduced peripheral but not central blood pressure, and higher pulse pressure amplification. Furthermore, left cardiac workload was increased in parallel with unfavourable changes in coronary perfusion conditions.

Interrelation between adult persons with diabetes and their family: a systematic review of the literature.

Diabetes mellitus is a common chronic disease all over the world. Self-management plays a crucial role in diabetes management. The purpose of this systematic review was to summarize what is known about the interactions between adult persons with diabetes, their family, and diabetes self-management. MEDLINE, CINAHL, PSYCHINFO, LINDA, and MEDIC databases were searched for the years 2000 to 2011 and for English language articles, and the reference lists of the studies included were reviewed to capture additional studies. The findings indicate that family members have influence on the self-management of adult persons with diabetes. The support from family members plays a crucial role in maintaining lifestyle changes and optimizing diabetes management. Diabetes and its treatment also affect the life of family members in several ways, causing, for example, different types of psychological distress. More attention should be paid to family factors in diabetes management among adult persons.

The impact of interprofessional education on students' current and desired competence in diabetes care.

AIM: To explore the impact of interprofessional education (IPE) on undergraduate nursing and medical students' knowledge, competence and targeted competence in diabetes care. DESIGN: Mixed methods design. METHODS: A voluntary IPE course of diabetes management was organized for nursing (n = 15) and medical (n = 15) students, who performed a diabetes knowledge test and self-evaluation of diabetes competence before and after the course and were compared with non-participating students. The participating students' focus-group interviews were analysed using inductive content analysis. RESULTS: The IPE course improved nursing students' diabetes knowledge and self-evaluated competence among nursing and medical students. The baseline differences in self-evaluated competence between the groups disappeared. The non-participating students evaluated their competence higher than the participants, though they scored lower or equally in the knowledge test. In conclusion, IPE showed potential in increasing students' self-evaluated competence, motivation to learn more and nursing students' diabetes knowledge, offering better prospects for future interprofessional diabetes management.

Immunohistochemical somatostatin receptor expression in insulinomas.

Insulinomas are rare pancreatic neuroendocrine tumours. Most patients can be cured with surgery, but patients with a metastatic disease show impaired survival. The aim of this study was to evaluate somatostatin receptor (SSTR) 1-5 expression in insulinomas and to correlate the expression profile with clinicopathological variables and with patient outcome. This retrospective study involved 52 insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with monoclonal SSTR1-5 antibodies. All the 52 tumours (49 non-metastatic, 3 metastatic) expressed at least one SSTR subtype. SSTR2 was expressed most frequently (71%), followed by SSTR3 (33%), SSTR1 (27%), SSTR5 (6%) and SSTR4 (0%). SSTR3 expression was associated with a larger tumour size (median diameter 19 mm vs. 13 mm, p = 0.043), and SSTR3 and SSTR5 expression were associated with impaired overall survival [HR 3.532 (95% CI 1.106-11,277), p = 0.033, and HR 6.805 (95% CI 1.364-33.955), p = 0.019 respectively]. Most insulinomas express SSTR2, which may be utilized in diagnostic imaging, and in planning individualized treatment strategies for insulinoma patients. Further studies are needed to clarify the association between SSTR profile and overall survival.

Gluten-free diet and autoimmune thyroiditis in patients with celiac disease. A prospective controlled study.

OBJECTIVE: Early diagnosis and dietary treatment with a gluten-free diet might slow down the progression of associated autoimmune diseases in celiac disease, but the data are contradictory. We investigated the course of autoimmune thyroid diseases in newly diagnosed celiac disease patients before and after gluten-free dietary treatment. MATERIAL AND METHODS: Twenty-seven consecutive adults with newly diagnosed celiac disease were investigated at the time of diagnosis and after 1 year on gluten-free diet. Earlier diagnosed and subclinical autoimmune thyroid diseases were recorded and examined. Thyroid gland volume and echogenicity were measured by ultrasound. Autoantibodies against celiac disease and thyroiditis, and thyroid function tests were determined. For comparison, 27 non-celiac controls on normal gluten-containing diet were examined. RESULTS: At the time of diagnosis, the celiac disease patients had more manifest (n = 7) or subclinical (n = 3) thyroid diseases than the controls (10/27 vs. 3/27, p = 0.055). During the follow-up, the thyroid volume decreased significantly in the patients with celiac disease compared with the controls, indicating the progression of thyroid gland atrophy despite the gluten-free diet. CONCLUSIONS: Celiac patients had an increased risk of thyroid autoimmune disorders. A gluten-free diet seemed not to prevent the progression of autoimmune process during a follow-up of 1 year.

Students' perceptions of interprofessional collaboration on the care of diabetes: A qualitative study.

Interprofessional education can promote healthcare professionals' competence to work in interprofessional collaboration, which is essential for the quality and safety of care. An interprofessional approach is particularly important in complex, chronic diseases like diabetes. This qualitative study evaluated changes in medical and nursing students' perceptions of interprofessional collaboration, induced by a novel interprofessional education course on diabetes care with practical elements. Data from focus-group interviews of 30 students before and after the course were analyzed by using inductive and deductive content analysis. The students' perceptions were illustrated as Elements of Collaborative Care (e.g. Quality of professional care relationship) and Elements of Interprofessional Collaboration (e.g. Importance of communication and Valuation of collaboration). The post-course interviews added one subcategory (Need of resources) to the pre-course perceptions, and there was improvement in ten areas of self-perceived competence in performing or understanding interprofessional collaboration on diabetes care. The course improved the students' self-perceived competence and confidence in interprofessional collaboration on the care of patients with diabetes, and their understanding of interprofessional collaboration changed towards a more patient-centred and holistic perspective. The findings support further implementation of IPE with practical elements in future health professionals' education.

Hormonal Defects Are Common during Puumala Hantavirus Infection and Associate with Disease Severity and Biomarkers of Altered Haemostasis.

Central and peripheral hormone deficiencies have been documented during and after acute hantavirus infection. Thrombocytopenia and coagulation abnormalities are common findings in haemorrhagic fever with renal syndrome (HFRS). The associations between coagulation and hormonal abnormalities in HFRS have not been studied yet. Forty-two patients diagnosed with Puumala virus (PUUV) infection were examined during the acute phase and on a follow-up visit approximately one month later. Hormonal defects were common during acute PUUV infection. Overt (clinical) hypogonadism was identified in 80% of the men and approximately 20% of the patients had overt hypothyroidism. At the one-month follow-up visit, six patients had central hormone deficits. Acute peripheral hormone deficits associated with a more severe acute kidney injury (AKI), longer hospital stay and more severe thrombocytopenia. Half of the patients with bleeding symptoms had also peripheral hormonal deficiencies. Patients with free thyroxine levels below the reference range had higher D-dimer level than patients with normal thyroid function, but no thromboembolic events occurred. Acute phase hormonal abnormalities associate with severe disease and altered haemostasis in PUUV infection.

Long-term morbidity and mortality in patients diagnosed with an insulinoma.

OBJECTIVE: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. DESIGN: Retrospective cohort study. METHODS: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. RESULTS: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). CONCLUSIONS: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.

Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection.

Most cases of hemorrhagic fever with renal syndrome (HFRS) in Europe are caused by the Puumala hantavirus (PUUV). Typical features of the disease are increased vascular permeability, acute kidney injury (AKI), and thrombocytopenia. YKL-40 is an inflammatory glycoprotein involved in various forms of acute and chronic inflammation. In the present study, we examined plasma YKL-40 levels and the associations of YKL-40 with disease severity in acute PUUV infection. A total of 79 patients treated in Tampere University Hospital during 2005-2014 were studied. Plasma YKL-40 was measured in the acute phase, the recovery phase, and one year after hospitalization. Plasma YKL-40 levels were higher during the acute phase compared to the recovery phase and one year after hospitalization (median YKL-40 142 ng/mL, range 11-3320, vs. 45 ng/mL, range 15-529, vs. 32 ng/mL, range 3-213, p < 0.001). YKL-40 level was correlated with the length of hospital stay (r = 0.229, p = 0.042), the levels of inflammatory markers-that is, blood leukocytes (r = 0.234, p = 0.040), plasma C-reactive protein (r = 0.332, p = 0.003), and interleukin-6 (r = 0.544, p < 0.001), and maximum plasma creatinine level (r = 0.370, p = 0.001). In conclusion, plasma YKL-40 levels were found to be elevated during acute PUUV infection and correlated with the overall severity of the disease, as well as with the degree of inflammation and the severity of AKI.

Increased long-term cardiovascular morbidity among patients treated with radioactive iodine for hyperthyroidism.

OBJECTIVE: Previous studies suggest that hyperthyroid patients remain at increased risk of cardiovascular morbidity after restoring euthyroidism. The aim of this study was to compare the rate and causes of hospitalization of hyperthyroid patients treated with radioactive iodine (RAI) with those of an age- and gender-matched reference population in a long-term follow-up study. PATIENTS AND MEASUREMENTS: A population-based cohort study with a median follow-up time of 9 years was conducted among 2611 hyperthyroid patients treated with RAI between 1969 and 2002 in Tampere University Hospital, and among 2611 reference subjects. Information on hospitalizations was obtained from the nationwide Hospital Discharge Registry. New events were analysed as the main outcome, including only the first hospitalization due to a given indication. RESULTS: The rate of hospitalization due to cardiovascular disease (CVD) was higher among patients with hyperthyroidism than among the control population [637.1 vs. 476.4 per 10 000 person-years, rate ratio (RR) 1.12, 95% confidence interval (CI) 1.03-1.21]. The risk remained elevated up to 35 years after the RAI treatment. Hospitalizations due to atrial fibrillation (RR 1.35), cerebrovascular disease (RR 1.31), diseases of other arteries and veins (RR 1.22), hypertension (RR 1.20) and heart failure (RR 1.48) were more frequent in the patients than controls, while no such difference was found for coronary artery disease. Hospitalizations due to cancer, infectious and gastrointestinal diseases, and fractures were also more common in patients than in controls. CONCLUSIONS: Hyperthyroidism increases hospitalizations due to CVDs. The excess risk is sustained decades after treatment. Patients treated for hyperthyroidism constitute a high-risk group for CVD and may benefit from preventive interventions.

Mechanisms of ethanol-induced degeneration in the developing, mature, and aging cerebellum.

The adverse effects of acute and chronic ethanol exposure on cerebellar functions have been acknowledged for decades, in terms of impaired control of movement and balance. In addition to the motor impairment, cerebellar degeneration has recently been shown to contribute to distinct neuropsychological deficits in chronic alcoholics, as well as in children with prenatal ethanol exposure. The basic mechanisms underlying these ethanol-induced functional alterations and the related neuropathology in the cerebellum have mostly been clarified only recently. These mechanisms include: (i) excitotoxicity; (ii) dietary factors, especially thiamine depletion; (iii) glial abnormalities; (iv) changes in growth factors; (v) apoptotic mechanisms; (vi) oxidative stress; and (vii) compromised energy production. Although these mechanisms widely apply not only to the mature cerebellum, but also to the developing and the aging cerebella, the developing and the aged cerebellum have some special characteristics, which may make them even more vulnerable to ethanol-induced degeneration. These special instances will be discussed along with the general mechanisms of ethanol-induced cerebellar degeneration.

Cardiovascular Morbidity and Mortality After Treatment of Hyperthyroidism with Either Radioactive Iodine or Thyroidectomy.

BACKGROUND: Hyperthyroid patients remain at an increased risk of cardiovascular diseases (CVDs) after restoring euthyroidism. The impact of the different treatment modalities of hyperthyroidism on future CVD risk remains unclear. The aims of this study were to assess cardiovascular morbidity and mortality in hyperthyroidism before and after treatment, and to compare the effects of two different treatment modalities: radioactive iodine (RAI) and thyroid surgery. METHODS: A comparative cohort study was conducted among 6148 hyperthyroid patients treated with either RAI or thyroidectomy and 18,432 age- and sex-matched controls. First, hospitalizations due to CVDs prior to the treatment were analyzed. Second, the hazard ratios (HR) for any new hospitalization and mortality due to CVDs after treatment were estimated among all the hyperthyroid patients compared to the age- and sex-matched controls and also in the RAI-treated patients compared to the thyroidectomy-treated patients. The results were adjusted for prevalent CVDs at the time of treatment. RESULTS: Before treatment for hyperthyroidism, hospitalizations due to all CVDs were more common in the hyperthyroid patients compared to the controls (odds ratio = 1.61 [confidence interval (CI) 1.49-1.73]). During the post-treatment follow-up, hospitalizations due to CVDs remained more frequent among the patients (HR = 1.15 [CI 1.09-1.21]), but there was no difference in CVD mortality (HR = 0.93 [CI 0.84-1.03]). Compared to the patients treated with thyroidectomy, the RAI-treated patients had a higher risk of hospitalization due to all CVDs (HR = 1.17), atrial fibrillation (HR = 1.28), as well as a higher CVD mortality rate (HR = 2.56). Yet, treatment with RAI resulting in hypothyroidism was not associated with increased CVD morbidity compared to thyroidectomy. CONCLUSIONS: Hyperthyroidism increases the risk of CVD-related hospitalization, and the risk is sustained for up to two decades after treatment with RAI or surgery. Hyperthyroid patients treated with RAI remain at a higher CVD risk compared to patients treated with thyroidectomy. Hypothyroidism during follow-up, however, predicts better cardiovascular outcomes.