Search

BACKGROUND It is unclear whether preoperative thyroid-stimulating hormone (TSH) level is correlated with long-term mortality in the elderly after hip fracture surgery. We aimed to assess the association between TSH levels and 3-year mortality in these patients. MATERIAL AND METHODS We enrolled patients aged 65 and above who had hip fracture surgery and thyroid function tests upon admission from 2018 to 2019. Patients were categorized based on TSH median value, quartiles, or thyroid function status. The median follow-up time was 3.1 years. Cox proportional hazards models were used to examine the correlation between TSH levels and mortality, adjusting for covariates. RESULTS Out of 799 eligible patients, 92.7% (741/799) completed the follow-up, with 20.6% (153/741) of those having died by the end of the follow-up. No statistically significant differences in mortality risks were found when stratified by TSH median value (HR 0.88, 95% CI 0.64-1.22, P=0.448) or quartiles (HR ranging from 0.90 to 1.13, P>0.05). Similarly, when categorized based on admission thyroid function status, patients who presented with hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism upon admission did not demonstrate a statistically significant difference in mortality risk compared to those who were considered euthyroid (HR 1.34, 95% CI 0.72-2.49, P=0.359; HR 0.77, 95% CI 0.38-1.60, P=0.489; HR 1.15, 95% CI 0.16-8.30, P=0.890; HR 1.07, 95% CI 0.34-3.38, P=0.913, respectively). CONCLUSIONS Admission TSH is not significantly associated with 3-year mortality in geriatric patients after hip fracture surgery.

Background: Thyroid-stimulating hormone (TSH) has been regarded as a predictor of poor outcomes in patients with acute myocardial infarction (AMI). AMI complicated by diabetes mellitus (DM) tends to have a high prevalence and a worse prognosis. We aim to evaluate the association between thyroid dysfunction and in-hospital outcomes and short- and medium-term mortality in diabetic patients with AMI., Methods: From January 2017 to November 2020, a total of 432 patients with AMI were included in this study, including 209 DM patients and 223 non-DM patients. Baseline characteristics, medical history, and laboratory parameters of patients were recorded after admission. In-hospital outcomes and 30-day mortality were recorded, and long-term mortality was recorded with a median follow-up of 34.2 ± 5.6 months., Results: Subclinical hypothyroidism (SCH) was defined as an elevated TSH level of more than with a normal range of circulating thyroid hormones. In AMI with DM group, 26/209 (12.4%) patients were complicated with SCH, these patients tend to be older and experienced worse in-hospital outcomes compared to patients without SCH, including higher rates of acute heart failure, acute kidney injury, and atrial fibrillation. Moreover, patients with SCH had a higher prevalence of 30-day mortality and long-term mortality, compared with patients without SCH., Conclusions: Diabetic AMI patients with SCH had worse in-hospital outcomes and higher 30-day and long-term mortality. Patients with diabetic AMI should pay attention to thyroid function, and SCH is an independent risk factor for short-term and long-term mortality in diabetic AMI patients.

There are a few studies and case reports that postulate a connection between hypothyroidism and reproductive disorders in bitches and an increased neonatal mortality and morbidity in puppies. Other studies, however, cannot demonstrate a connection between hypothyroidism and reproductive disorders in bitches. In this work, the relevant literature is to be checked for its evidence. The connection between hypothyroidism and reproductive disorders in the bitch, puppy mortality and neonatal morbidity to hypothyroidism will be analyzed based on a literature review. For this purpose, the available German and international "English-language" literature from 1986 to January 2023 was analyzed. It turns out that only a small amount of literature contains high levels of scientific evidence, as it mostly consists of case reports and expert opinions. In some case reports a connection between estrous abnormalities, galactorrhoea and infertility and the presence of hypothyroidism could be seen, but in experimental studies and according to the opinion of other authors the connection between hypothyroidism and reproductive disorders does not exist. A negative influence of hypothyroidism on the birth process could not be clearly proven. In an experimental study, although the duration and intensity of uterine contractions were longer and weaker in animals with hypothyroidism, the interval between pup births was not affected. Only in the area of neonatal mortality and morbidity a connection with the hypothyroidism of the dam could be demonstrated. The puppies of affected bitches showed a lower birth weight and were weaker than puppies of euthyroid bitches. The importance of hypothyroidism for fertility in the bitch has not yet been documented in the literature, but this endocrinopathy seems to have an influence on neonatal vitality., Competing Interests: Die Autoren bestätigen, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Chronic systolic heart failure (CSHF) is a significant health burden with high morbidity and mortality. The role of subclinical hypothyroidism (SCH) in the prognosis of CSHF patients remains a critical area of inquiry. This systematic review and meta-analysis aim to elucidate the impact of SCH on the prognosis of patients with CSHF., Methods: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, this meta-analysis employed a comprehensive search strategy across major databases including PubMed, Embase, Web of Science, and the Cochrane Library. The Patient, Intervention, Comparison, Outcome framework guided the inclusion of studies focusing on patients with CSHF, comparing those with and without SCH. Quality assessment was performed using the Newcastle-Ottawa scale. Statistical analyses assessed heterogeneity and publication bias, employing fixed-effect or random-effects models based on heterogeneity levels., Results: From an initial pool of 1439 articles, 8 studies met the stringent inclusion criteria. These studies, conducted across diverse geographical regions, highlighted the relationship between SCH and all-cause mortality, cardiac events, and subgroup differences in CSHF patients. The meta-analysis revealed SCH as a significant risk factor for all-cause mortality (HR = 1.42) and cardiac events (HR = 1.46). Subgroup analysis indicated variability in risk based on region, sample size, age, and follow-up duration. Sensitivity analysis confirmed the stability of these findings, and publication bias assessment indicated symmetric funnel plot and nonsignificant Egger test results., Conclusions: SCH emerges as a predictive factor for all-cause mortality, cardiovascular events, and rehospitalization in CSHF patients. This finding underscores the importance of screening for SCH in CSHF patients, highlighting its potential role in improving patient prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Although hypothyroidism is associated with various comorbidities, its relationship with increased all-cause mortality remains controversial. The aim of this nationwide retrospective cohort study was to investigate whether hypothyroid patients treated with levothyroxine had increased mortality compared to controls., Methods: Hypothyroid subjects were identified through the Korean National Health Insurance Service Claims database between 2008 and 2017. Hypothyroidism in this study was defined as overt hypothyroidism treated with long-term prescription of levothyroxine (>6 months). After 1:3 age-, sex- and index year-matching, 501,882 patients with newly diagnosed hypothyroidism and 1,505,646 controls without hypothyroidism were included., Results: During a mean follow-up of 6 years, 25,954 (5.2%) hypothyroid patients and 59,105 (3.9%) controls died. Hypothyroidism was significantly associated with increased all-cause mortality (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI] 1.12-1.16) even with levothyroxine treatment. When stratified by age, sex, and cardiovascular disease risk, independent associations between hypothyroidism and mortality remained significant in all subgroups. The risk of mortality was higher in the < 65 age group (HR: 1.25, 95% CI: 1.22-1.29), men (HR: 1.28, 95% CI: 1.25-1.31), and the high cardiovascular disease risk group (HR: 1.31, 95% CI: 1.29-1.34). The mortality rate of hypothyroid patients was highest within 1 year of treatment and decreased with time., Conclusion: This nationwide, population-based cohort study showed that all-cause mortality was significantly higher in levothyroxine-treated hypothyroid patients than in non-hypothyroid controls. This association remained significant regardless of age, sex, and cardiovascular disease risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sohn, Seo and Chung.)

Background: Subclinical and overt thyroid dysfunction is easily detectable, often modifiable, and, in younger age groups, has been associated with clinically relevant outcomes. Robust associations in very old persons, however, are currently lacking. This study aimed to investigate the associations between (sub-)clinical thyroid dysfunction and disability in daily living, cognitive function, depressive symptoms, physical function, and mortality in people aged 80 years and older. Methods: Four prospective cohorts participating in the Towards Understanding Longitudinal International older People Studies (TULIPS) consortium were included. We performed a two-step individual participant data meta-analysis on source data from community-dwelling participants aged 80 years and older from the Netherlands, New Zealand, United Kingdom, and Japan. Outcome measures included disability in daily living (disability in activities of daily living [ADL] questionnaires), cognitive function (Mini-Mental State Examination [MMSE]), depressive symptoms (Geriatric Depression Scale [GDS]), physical function (grip strength) at baseline and after 5 years of follow-up, and all-cause five-year mortality. Results: Of the total 2116 participants at baseline (mean age 87 years, range 80-109 years), 105 participants (5.0%) were overtly hypothyroid, 136 (6.4%) subclinically hypothyroid, 1811 (85.6%) euthyroid, 60 (2.8%) subclinically hyperthyroid, and 4 (0.2%) overtly hyperthyroid. Participants with thyroid dysfunction at baseline had nonsignificantly different ADL scores compared with euthyroid participants at baseline and had similar MMSE scores, GDS scores, and grip strength. There was no difference in the change of any of these functional measures in participants with thyroid dysfunction during five years of follow-up. Compared with the euthyroid participants, no 5-year survival differences were identified in participants with overt hypothyroidism (hazard ratio [HR] 1.0, 95% confidence interval [CI 0.6-1.6]), subclinical hypothyroidism (HR 0.9 [CI 0.7-1.2]), subclinical hyperthyroidism (HR 1.1 [CI 0.8-1.7]), and overt hyperthyroidism (HR 1.5 [CI 0.4-5.9]). Results did not differ after excluding participants using thyroid-influencing medication. Conclusions: In community-dwelling people aged 80 years and older, (sub-)clinical thyroid dysfunction was not associated with functional outcomes or mortality and may therefore be of limited clinical significance.

Background: Subclinical hypothyroidism (SCH) is reportedly associated with an increased risk of adverse events in patients undergoing percutaneous coronary intervention (PCI). The prognostic significance of SCH in the elderly was poorly defined. The purpose of this study was to evaluate the association between SCH and long-term outcomes in older patients undergoing PCI., Methods: Three thousand one hundred sixty-eight patients aged 65 years or older who underwent PCI from January 2012 to October 2014 were included. Patients were divided into SCH group (n = 320) and euthyroidism (ET) group (n = 2848) based on thyroid function test. Cox proportional hazard regression analyses were used to estimate the relative risks (RRs) of all-cause death and cardiac death for patients with SCH during a 4-year follow-up period., Results: There were 227 deaths during the follow-up period including 124 deaths caused by cardiac events. There was no significant difference in mortality rate between the SCH group and the ET group (p > 0.05). After adjustment for covariates, compared with patients with ET, the RRs of death from all-cause and cardiac in patients with SCH were 1.261 (95%CI: 0.802-1.982, p = 0.315) and 1.231 (95%CI: 0.650-2.334, p = 0.524), respectively. When SCH was stratified by age, gender, and degree of thyroid-stimulating hormone elevation, no significant associations were also found in any stratum., Conclusion: Our investigation revealed that SCH was negatively associated with the outcome of PCI in older patients.

Since the introduction of sensitive assays for serum thyroid-stimulating hormone (TSH) clinicians have advised hypothyroid patients to adjust the dose of levothyroxine (L-T4) in order to achieve a normal serum TSH. A minority of patients are dissatisfied with this treatment strategy and experience symptoms. Some indirect evidence suggests that a normal serum TSH may not necessarily reflect euthyroidism at the tissue level in patients treated with L-T4. Increasingly hypothyroid patients demand higher doses of L-T4 or liothyronine (L-T3) or animal thyroid extract, often purchased online, and titrate the dose against symptoms, although ample evidence suggests that combination treatment (L-T4 with L-T3) is no more effective than L-T4 alone. Community surveys show that up to 53% of treated hypothyroid patients at any time have a serum TSH outside the normal range. The recommendation by guidelines that the upper limit of the normal range for serum TSH should not be exceeded is supported by robust evidence and is generally accepted by clinicians and patients. However, until recently the lower limit of serum TSH for optimal L-T4 replacement has been controversial. New evidence obtained by two independent large population studies over the past two years has shown that mortality of hypothyroid patients treated with levothyroxine is increased when the serum TSH exceeds or is reduced outside the normal reference range. It is estimated that the implementation of a policy of normalising serum TSH in hypothyroid patients will reduce the risk of death of 28.3 million people in the USA and Europe alone.

Context: Benefits of thyroid hormone therapy on mortality in adults with subclinical hypothyroidism remain undetermined., Objective: To summarize the impact of thyroid hormone therapy on mortality in adults with subclinical hypothyroidism., Data Sources: PubMed, Embase, Scopus, Web of Science, and Clinicaltrials.gov from inception until April 25, 2020., Study Selection: Studies comparing the effect of thyroid hormone therapy with that of placebo or no therapy in adults with subclinical hypothyroidism on all-cause and/or cardiovascular mortality., Data Extraction: Two reviewers independently extracted data and performed quality assessments. Random-effects models for meta-analyses were used., Data Synthesis: Five observational studies and 2 randomized controlled trials with 21 055 adults were included. Overall, thyroid hormone therapy was not significantly associated with all-cause (pooled relative risk [RR] = 0.95, 95% confidence interval [CI]: 0.75-1.22, P = .704) or cardiovascular (pooled RR = 0.99, 95% CI: 0.82-1.20, P = .946) mortality. Subgroup analyses revealed that in younger adults (aged <65-70 years), thyroid hormone therapy was significantly associated with a lower all-cause (pooled RR = 0.50, 95% CI: 0.29-0.85, P = .011) and cardiovascular (pooled RR = 0.54, 95% CI: 0.37-0.80, P = .002) mortality. However, no significant association between thyroid hormone therapy and mortality was observed in older adults (aged ≥65-70 years)., Conclusions: Use of thyroid hormone therapy does not provide protective effects on mortality in older adults with subclinical hypothyroidism. However, thyroid hormone therapy for subclinical hypothyroidism may show benefits on morality in adults aged <65 to 70 years., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In patients with COVID-19, certain medical conditions could result in poorer clinical outcomes. However, the prognostic role of hypothyroidism in COVID-19 is still unknown. In the present retrospective study, we estimated the prevalence of hypothyroidism in COVID-19 admitted patients in Tehran, Iran. Among 390 COVID-19 admitted patients, 21 hypothyroid cases (5.4%) were found, in which nearly 90% were aged 50 years and older. Regarding the effect of hypothyroidism on COVID-19 mortality, 60 (15.3%) of total patients and 4 (19%) of hypothyroid patients died, and no significant difference was found between the two groups., (© 2020 Royal Australasian College of Physicians.)

Background: Hypothyroidism is known to be associated with adverse clinical outcomes in heart failure. The association between hypothyroidism and cardiac resynchronization therapy outcomes in patients with severe heart failure is not clear., Methods: The study included 1316 patients who received cardiac resynchronization therapy between 2002 and 2015. Baseline demographics and cardiac resynchronization therapy outcomes, including left ventricular ejection fraction, New York Heart Association class, appropriate implantable cardioverter-defibrillator therapy, and all-cause mortality, were collected from the electronic health record., Results: Of the study cohort, 350 patients (26.6%) were classified as the hypothyroidism group. The median duration of follow-up was 3.6 years (interquartile range, 1.7-6.2 years). Hypothyroidism was not associated with a higher risk of all-cause mortality in patients receiving CRT for heart failure. The risk of appropriate implantable cardioverter-defibrillator therapy significantly increased in association with increased baseline thyroid-stimulating hormone level in the entire cohort (hazard ratio, 1.23 per 5mIU/L increase; 95% CI, 1.01-1.5; P = 0.04) as well as in the hypothyroid group (hazard ratio, 1.44 per 5mIU/L increase; 95% CI, 1.13-1.84; P = 0.004)., Conclusions: CRT improves cardiac function in hypothyroid patients. The ventricular arrhythmic events requiring ICD therapies are associated with baseline TSH level, which might be considered as an important biomarker to stratify the risk of sudden death for patients with heart failure and hypothyroidism.

Introduction: Higher levels of thyroid-stimulating hormone (TSH) in the euthyroid state can negatively affect the metabolic health, including nonalcoholic fatty liver disease (NAFLD). We studied the effect of TSH levels in the setting of normal levels of thyroid hormone on all-cause and cause-specific mortality stratified by NAFLD status., Methods: The National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and NHANES III-linked mortality data through 2015 were used. NAFLD was defined as ultrasonographically diagnosed hepatic steatosis without coexisting liver diseases. Subclinical hypothyroidism was defined as a TSH level over 4.5 mIU/L and "low-normal" thyroid function as higher TSH level (2.5-4.5 mIU/L) within the euthyroid reference range. The Cox proportional hazard model analyzed the all-cause mortality and cause-specific mortality., Results: In a multivariate logistic regression analysis, individuals with low thyroid function demonstrated an association with NAFLD in a dose-dependent manner. During a median follow-up of 23 years, low thyroid function was associated with increased all-cause mortality only in the univariate model. Low thyroid function was associated with a higher risk for all-cause mortality in individuals with NAFLD and not in those without NAFLD. Furthermore, low thyroid function was associated with a higher risk for cardiovascular mortality in the entire population and among those with NAFLD but demonstrated no association with the non-NAFLD group., Discussion: In this large nationally representative sample of American adults, low thyroid function was associated with NAFLD and a predictor of higher risk for all-cause and cardiovascular mortality in individuals with NAFLD.

Coronavirus diseases (COVID-19) is associated with high rates of morbidity and mortality and worse outcomes have been reported for various morbidities. The impact of pre-existing hypothyroidism on COVID-19 outcomes remains unknown. The aim of the present study was to identify a possible association between hypothyroidism and outcomes related to COVID-19 including hospitalization, need for mechanical ventilation, and all-cause mortality. All patients with a laboratory confirmed COVID-19 diagnosis in March 2020 in a large New York City health system were reviewed. Of the 3703 COVID-19 positive patients included in present study, 251 patients (6.8%) had pre-existing hypothyroidism and received thyroid hormone therapy. Hypothyroidism was not associated with increased risk of hospitalization [Adjusted Odds Ratio (OR adj ): 1.23 (95% Confidence Interval (CI): 0.88- 1.70)], mechanical ventilation [OR adj : 1.17 (95% CI: 0.81-1.69)] nor death [OR adj : 1.07 (95% CI: 0.75-1.54)]. This study provides insight into the role of hypothyroidism on the outcomes of COVID-19 positive patients, indicating that no additional precautions or consultations are needed. However, future research into the potential complications of COVID-19 on the thyroid gland and function is warranted., (Copyright © 2020 van Gerwen, Alsen, Little, Barlow, Naymagon, Tremblay, Sinclair and Genden.)

Background: Several preclinical and epidemiologic studies have indicated tumour-promoting effects of thyroid hormones (THs). However, very limited knowledge exists on the prognostic impact of thyroid function in metastatic cancer., Methods: We compiled a discovery cohort of 1692 patients with newly diagnosed brain metastases (BMs) of solid cancers treated at the Medical University of Vienna and an independent validation cohort of 191 patients with newly diagnosed BMs treated at the University Hospital Zurich., Results: Hypothyroidism before diagnosis of cancer was evident in 133 of 1692 (7.9%) patients of the discovery, and in 18 of 191 (9.4%) patients of the validation cohort. In the discovery cohort, hypothyroidism was statistically significantly associated with favourable survival prognosis from diagnosis of cancer (31 vs. 21 months; p = 0.0026) and with survival prognosis from diagnosis of BMs (12 vs. 7 months; p = 0.0079). In multivariate analysis including the diagnosis-specific graded prognostic assessment score, primary tumour type and sex, hypothyroidism was an independent factor associated with survival after diagnosis of BMs (hazard ratio: 0.76; 95% confidence interval [CI]: (0.63; 0.91; p = 0.0034). In the validation cohort, the association of hypothyroidism and favourable survival prognosis from diagnosis of cancer (55 vs. 11 months; p = 0.00058), as well as from diagnosis of BMs (40 vs. 10 months; p = 0.0036) was confirmed., Conclusion: Pre-existing hypothyroidism was strongly and independently associated with prognosis in patients with newly diagnosed BMs, supporting the evidence from preclinical data that THs may indeed have a tumour-promoting effect. Further investigation of the underlying pathobiological mechanism and potential therapeutic implications are required., Competing Interests: Conflict of interest statement A.S.B. has received research support from Daiichi Sankyo (≤10000€), Roche (>10000€); has received honoraria for lectures;has been a member of the consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo (all < 5000€), has received travel support from Roche, Amgen and AbbVie. M.K. has received research support from Sanofi, AstraZeneca and Ipsen; served as a speaker and received consulting fees from AstraZeneca, Novartis, Novo Nordisk, Lilly, Merck, Böhringer, Roche and Sanofi. M.W. has received research grants from Abbvie, Adastra, Bristol Meyer Squibb (BMS), Dracen, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Piqur and Roche; has received honoraria for lectures or served as a member of advisory board participation or consulting from Abbvie, Basilea, Bristol Meyer Squibb (BMS), Celgene, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Orbus, Roche and Tocagen. M.P. has received research support from Böhringer-Ingelheim, GlaxoSmithKline, Merck Sharp & Dome and Roche; has received honoraria for lectures; served as a member of the consultation or advisory board participation (all < 5000€) from Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Merck Sharp & Dome. All the other authors have no conflicts of interest to declare., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Context: The evidence of whether hypothyroidism increases mortality in the elderly population is currently inconsistent and conflicting., Objective: The objective of this meta-analysis is to determine the impact of hypothyroidism on mortality in the elderly population., Data Sources: PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched from inception until May 10, 2019., Study Selection: Studies evaluating the association between hypothyroidism and all-cause and/or cardiovascular mortality in the elderly population (ages ≥ 60 years) were eligible., Data Extraction: Two reviewers independently extracted data and assessed the quality of the studies. Relative risk (RR) was retrieved for synthesis. A random-effects model for meta-analyses was used., Data Synthesis: A total of 27 cohort studies with 1 114 638 participants met the inclusion criteria. Overall, patients with hypothyroidism experienced a higher risk of all-cause mortality than those with euthyroidism (pooled RR = 1.26, 95% CI: 1.15-1.37); meanwhile, no significant difference in cardiovascular mortality was found between patients with hypothyroidism and those with euthyroidism (pooled RR = 1.10, 95% CI: 0.84-1.43). Subgroup analyses revealed that overt hypothyroidism (pooled RR = 1.10, 95% CI: 1.01-1.20) rather than subclinical hypothyroidism (pooled RR = 1.14, 95% CI: 0.92-1.41) was associated with increased all-cause mortality. The heterogeneity primarily originated from different study designs (prospective and retrospective) and geographic locations (Europe, North America, Asia, and Oceania)., Conclusions: Based on the current evidence, hypothyroidism is significantly associated with increased all-cause mortality instead of cardiovascular mortality among the elderly. We observed considerable heterogeneity, so caution is needed when interpreting the results. Further prospective, large-scale, high-quality studies are warranted to confirm these findings., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Thyroid hormone modifies metabolic, immune and cardiovascular functions and has been administered perioperatively to treat a relative reduction of thyroid function in children following cardiopulmonary bypass (CPB) for correction of congenital heart disease. However, it remains unclear whether its use is associated with improved outcomes. We performed a meta-analysis of studies that evaluated the impact of thyroid hormone supplementation on clinical outcomes in children undergoing repair of congenital heart disease using CPB. A systematic review of published trials was conducted to identify studies of children randomized to thyroid hormone supplementation or placebo undergoing congenital heart surgery. A meta-analysis was then conducted to determine the clinical impact of thyroid hormone replacement on cardiac function and postoperative characteristics. The following outcomes were included for the study: duration of mechanical ventilation, duration of intensive care unit (ICU) stay, duration of postoperative hospital stay, inotrope score, cardiac index at 24 hours postoperatively, and inpatient mortality. A total of 9 studies with 711 patients were included in the analyses. All included studies were prospective and patients were randomized to either thyroid hormone or placebo. There was wide variation in thyroid hormone dosing, ranging from 0.4 μg/kg up to 5 μg/kg over a 24-hour period, and duration of therapy, ranging from a single dose after cessation of CPB to continued thyroid hormone for the duration of the ICU stay. There was a significant difference in the mean inotrope score between the 2 groups of -1.249 (95% confidence interval -1.570 to -0.929, P < 0.001), with the inotrope score being significantly lower in the thyroid group. There was no difference in duration of mechanical ventilation, duration of ICU stay, duration of hospital stay, cardiac index, and mortality between groups. In this meta-analysis, routine thyroid hormone replacement with approximately 1-5 μg/kg administered over 24 hours does not significantly alter the postoperative course in children following CPB. However, given a clinically small but significant difference in respect to lower inotrope score and shorter duration of ICU and hospital stays with higher thyroid replacement additional studies are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To use a nationwide database of hospital admissions to assess for trends in inpatient mortality from acute spontaneous intracerebral hemorrhage as well as associated potentially contributing factors., Methods: Adults with intracerebral hemorrhage in the US National Inpatient Sample database from 2012 to 2015 were included in this study. We assessed for mortality rate as well as potential impact of various comorbidities and demographic factors such as ethnicity and median house hold income on inpatient mortality rate., Results: A total of 47,700 patients were identified with a mean age of 68 years. The overall mortality rate was 24%. Hypertension was the commonest comorbidity (84%) followed by diabetes mellitus (28%). Positive associated factors for mortality rate were coagulopathy (OR 1.28, 95% CI 1.19-1.38, P < .001), female gender (OR 1.12, 95% CI 1.08-1.17, P < .001), and congestive heart failure (OR 1.16, 95% CI 1.08-1.24, P < .001). Age greater than 75 was also associated with higher mortality (P < .001). Factors associated with reduced mortality were hypertension (OR .76, 95% CI .72-0.81, P < .001), hypothyroidism (OR .87, 95% CI .81-.93, P < .001) and obesity (OR .64, 95% CI .59-.69, P < .001)., Conclusions: The inpatient mortality of 24% represents a decline when compared to previous years. Attention to the associated factors with mortality, that we report, could have some potential impact on management. Of interest, we found support for obesity paradox in which obesity may have an actual salutary effect on vascular disease outcome. Our observed paradoxical effects, not only for obesity, but also hypertension and hypothyroidism, warrant further study., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Subclinical hypothyroidism is a common clinical entity among US adults associated in some studies with an increase in the risk of cardiovascular disease (CVD) and mortality. However, the extent to which CVD mediates the association between elevated serum thyrotropin (TSH) and mortality has not yet been well established or sufficiently quantified., Objective: To elucidate the extent to which subclinical hypothyroidism, elevated serum TSH and normal serum free thyroxine, or high-normal TSH concentrations (ie, upper normative-range TSH concentrations) are associated with mortality through CVD among US adults., Design, Setting, and Participants: This cohort study relied on representative samples of US adults enrolled in the National Health and Nutrition Examination Survey in 2001 to 2002, 2007 to 2008, 2009 to 2010, and 2011 to 2012 and their mortality data through 2015. Data were analyzed from January to August 2019., Main Outcomes and Measures: Cox proportional hazards regression models were used to investigate associations between the TSH concentration category (subclinical hypothyroidism or tertiles of serum TSH concentrations within the reference range; low-normal TSH, 0.34-1.19 mIU/L; middle-normal TSH, 1.20-1.95 mIU/L; and high-normal TSH, 1.96-5.60 mIU/L) and all-cause mortality. Mediation analysis was used within the counterfactual framework to estimate natural direct associations (not through CVD) and indirect associations (through CVD)., Results: Of 9020 participants, 4658 (51.6%) were men; the mean (SD) age was 49.4 (17.8) years. Throughout follow-up (median [interquartile range], 7.3 [5.4-8.3] years), serum thyroid function test results consistent with subclinical hypothyroidism and high-normal TSH concentrations were both associated with increased all-cause mortality (subclinical hypothyroidism: hazard ratio, 1.90; 95% CI, 1.14-3.19; high-normal TSH: hazard ratio, 1.36; 95% CI, 1.07-1.73) compared with the middle-normal TSH group. Cardiovascular disease mediated 14.3% and 5.9% of the associations of subclinical hypothyroidism and high-normal TSH with all-cause mortality, respectively, with the CVD mediation being most pronounced in women (7.5%-13.7% of the association) and participants aged 60 years and older (6.0%-14.8% of the association)., Conclusions and Relevance: In this study, CVD mediated the associations of subclinical hypothyroidism and high-normal TSH concentrations with all-cause mortality in the US general population. Further studies are needed to examine the clinical benefit of thyroid hormone replacement therapy targeted to a middle-normal TSH concentration or active CVD screening for people with elevated TSH concentrations.

Subclinical thyroid dysfunction (STD), presenting as subclinical hypothyroidism (SHypo) or subclinical hyperthyroidism (SHyper), defined as abnormal serum thyrotropin (TSH) and normal free thyroid hormones, is associated with increased cardiovascular (CV) risk and mortality. Depending on the degree of such dysfunction, atherosclerosis, coronary artery disease, heart failure and cardiac arrhythmias, predominantly atrial fibrillation, characterize both disorders and increase CV and total mortality compared to euthyroid persons. There are some differences in the mechanisms involved in the increased CV risk incurred by each type of STD, with more traditional CV risk factors clustered in SHypo than in SHyper, while the role of the TSH or its absence thereof, together with the respective, even subtle, changes incurred in thyroid hormone concentrations, seem to adversely influence the CV system in both types of STD. There is evidence that treatment of STD confers potential benefits by reducing CV events, however, no consensus has been reached due to lack of randomized controlled studies. Nevertheless, due to accumulating evidence from observational studies, many authorities agree that individuals with severe SHypo (TSH > 10 mIU/L) or grade 2 SHyper (TSH < 0.1 mIU/L) should receive treatment, mostly for the increased risk of CV morbidity and mortality. The evidence reviewed herein should alert and help the clinician to wake up to these two potentially alarming conditions of STD as they may confer serious CV complications, while their treatment appears quite beneficial., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Thyroid hormones profoundly influence the cardiovascular system, but the effects of mild thyroid dysfunction on the clinical outcome of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) are not well defined. This study aimed to determine the effect of mild thyroid dysfunction on 12-month prognosis in ACS patients undergoing PCI., Methods: In this prospective cohort study with a 12-month follow-up, 1560 individuals were divided into four groups based on thyroid hormone levels upon admission: euthyroidism (used as a reference group), subclinical hypothyroidism, subclinical hyperthyroidism, and low triiodothyronine syndrome (low T3 syndrome). The outcomes measured were all-cause mortality, cardiac mortality, nonfatal rein-farction, and unplanned repeat revascularization., Results: In this study, the prevalence of mild thyroid dysfunction was 10.8%. Multivariate analysis showed that low T3 syndrome, but not subclinical hypothyroidism or subclinical hyperthyroidism, was associated with a higher rate of all-cause (HR 2.553, 95% CI 1.093-5.964, p = 0.030) and cardiac mortality (HR 2.594, 95% CI 1.026-6.559, p = 0.034), compared with the euthyroidism group., Conclusions: Mild thyroid dysfunction was frequent in patients with ACS undergoing PCI. Low T3 syndrome was the predominant feature and was associated with 12-month adverse outcomes in these patients.

This study investigated the incidence of transient hypothyroxinaemia of prematurity (THOP) associated with survival without composite morbidities and the predictability of THOP severity in extremely low birth weight infants (ELBWIs). We retrospectively reviewed the medical records of 546 ELBWIs who underwent initial thyroid function tests within 14 postnatal days, with 156 ELBWIs from 2000 to 2005 (period I) and 390 from 2006 to 2013 (period II). The infants were stratified into 23-24, 25-26 and 27-28 weeks' gestation subgroups within each period; the initial thyroxine (T4) level, mortality, clinical characteristics and composite morbidities, including bronchopulmonary dysplasia, intraventricular haemorrhage, necrotizing enterocolitis, and retinopathy of prematurity were analysed. The predictive value of the initial T4 level, Apgar score at 5 min, and clinical risk index for babies II (CRIB II) score for estimating mortality and survival with or without composite morbidities was assessed. Comparing period II and period I, the incidence of THOP was significantly decreased along with significantly increased survival without composite morbidities in ELBWIs at 25-28 weeks' gestation. The severity of THOP showed significant associations with mortality and composite morbidities. The initial T4 level was most effective for predicting outcome compared with Apgar and CRIB II scores.

Background: There is an unmet need for markers predicting the outcome of patients with advanced soft tissue sarcoma (STS) treated with pazopanib. Since toxicity might be related to the anti-tumor activity of the drug, the aim of this study was to determine whether pazopanib-induced proteinuria, hypothyroidism and cardiotoxicity grade 3-4 were associated with outcome. Methods: The combined results of the EORTC 62043 and 62072 trials were retrospectively assessed and used in a landmark analysis to evaluate the effect of the toxicities on progression-free survival (PFS) and overall survival (OS), using the Kaplan-Meier method and Cox regression models. Results: Of the 333 eligible patients, 259 patients were included in the analyses, for which a landmark time point of 60 days after randomization/registration was selected. Proteinuria occurred in 25.1%, hypothyroidism in 22.0% and cardiotoxicity grade 3-4 in 5.8% of the patients (any grade in 41.7%). There was no effect of the occurrence of proteinuria (6-months PFS 35.4% for patients with vs. 38.3% for patients without proteinuria, HR 1.01, p  = .953), hypothyroidism (41.2% vs. 36.5%, HR 0.82, p  = .210) or cardiotoxicity grade 3-4 (26.7% vs. 38.2%, HR 0.97, p  = .897) on PFS. Nor was there an effect of proteinuria (6-months OS 63.2% for patients with vs. 74.4% for patients without proteinuria, HR 1.22, p  = .196), hypothyroidism (76.2% vs. 70.5%, HR 0.75, p  = .093) or cardiotoxicity grade 3-4 (80.0% vs. 77.2%, HR 0.93, p  = .801) on OS. Conclusion: There was no association between the occurrence of pazopanib-induced proteinuria, hypothyroidism and cardiotoxicity and outcome. Therefore, these toxicities cannot be used as predictors for pazopanib activity in patients with advanced STS.

Background: Subclinical thyroid dysfunction whose typical patterns include subclinical hypothyroidism and subclinical hyperthyroidism, has been indicated to be associated with an increased risk of heart failure (HF). However, the relationship between subclinical thyroid dysfunction and the clinical outcomes of HF patients is uncertain. This meta-analysis was conducted to assess the association between subclinical thyroid dysfunction and the clinical outcomes of HF patients., Methods: Pubmed, Embase, Web of Science and Cochrane Central Register of Clinical Trials were searched for eligible studies published up to August 1, 2018 which reported the association between subclinical thyroid dysfunction and the clinical outcomes of HF patients. The pooled hazard ratio (HR) with the corresponding 95% confidence interval (CI) was used to assess the association., Results: Fourteen studies met the eligibility criteria and a total of 21,221 patients with heart failure were included in the meta-analysis. Compared with HF patients with euthyroidism, the pooled HR of subclinical hypothyroidism for all-cause mortality was 1.45 (95% CI 1.26-1.67) in a randomized effects model with mild heterogeneity (I 2  = 40.1, P = 0.073). The pooled HR of subclinical hypothyroidism for cardiac death and/or hospitalization was 1.33 (1.17-1.50) in a randomized effects model with moderate heterogeneity (I 2  = 69.4, P < 0.001). Subclinical hyperthyroid can increase the risk of all-cause mortality without heterogeneity (HR 1.31, 95% CI 1.10-1.55, I 2  = 25.5%, P = 0.225) but have no influence on the risk of cardiac death and/or hospitalization (HR 1.03, 95% CI 0.87-1.23, I 2  = 0.0%, P = 0.958). These significant adverse associations were also retained in subgroup analysis. Sensitivity analysis demonstrated the stability of the results of our meta-analysis., Conclusions: Both subclinical hypothyroidism and subclinical hyperthyroidism are associated with adverse prognosis in patients with HF. Subclinical thyroid dysfunction may be a useful and promising predictor for the long-term prognosis in HF patients.

Objectives: To determine the impact of subclinical hypothyroidism (SCH) on the risk of cardiovascular disease (CVD) and all-cause mortality, a comprehensive meta-analysis was performed according to the age or coexisting CVD risk status of the participants., Methods: Studies regarding the association of SCH with all-cause mortality from PubMed and Embase databases were included. The pooled relative risk (RR) of CVD and all-cause mortality was calculated using the Mantel-Haenszel method. A subgroup analysis of participants with high CVD risk was conducted, including history of coronary, cerebral, or peripheral artery disease; dilated cardiomyopathy; heart failure; atrial fibrillation; venous thromboembolism; diabetes mellitus; or chronic kidney disease., Results: In total, 35 eligible articles incorporating 555,530 participants were included. SCH was modestly associated with CVD and all-cause mortality (RR for CVD = 1.33 [confidence interval (CI) 1.14-1.54]; RR for all-cause mortality = 1.20 [CI 1.07-1.34]). However, the association was not observed in participants aged ≥65 years. Subgroup analysis showed that participants with SCH and high CVD risk showed a significantly higher risk of all-cause mortality (RR for CVD = 2.20 [CI 1.28-3.77]; RR for all-cause mortality = 1.66 [CI 1.41-1.94]), whereas those with SCH and low CVD risk did not. Additional subgroup analysis of six studies with a mean participant age of ≥65 years and high CVD risk showed a significant high risk of all-cause mortality in the SCH group (RR = 1.41 [CI 1.08-1.85]; I 2  = 0%)., Conclusions: SCH is associated with an increased CVD risk and all-cause mortality, particularly in participants with high CVD risk.

Context: Although hypothyroidism is associated with many comorbidities, the evidence for its association with all-cause mortality in older adults is limited., Objective: To evaluate the association between hypothyroidism and all-cause mortality in older adults., Design: Population-based retrospective cohort study., Setting: National Health Insurance Research Database in Taiwan., Patients: After 1:10 age/sex/index year matching, 2029 patients aged ≥65 years who received a new diagnosis of hypothyroidism between 2001 and 2011 and 20,290 patients without hypothyroidism or other thyroid diseases were included in the hypothyroidism and nonhypothyroidism cohorts, respectively., Main Outcome Measures: All-cause mortality was defined as the primary outcome. Cox proportional hazards regression models were used to calculate the hazard ratios of mortality. To further evaluate the effect of thyroxine replacement therapy (TRT) on mortality, we divided patients with hypothyroidism into two groups: patients who received TRT and those who did not., Results: Hypothyroidism was associated with an increased risk of all-cause mortality [adjusted hazard ratio (aHR), 1.82; 95% CI, 1.68 to 1.98; P < 0.001]. Patients with hypothyroidism who received TRT had a lower risk of mortality than patients who did not receive TRT (aHR, 0.57; 95% CI, 0.49 to 0.66; P < 0.001). Similar results were obtained after further propensity score matching in age-, sex-, and comorbidity-stratified analyses., Conclusions: Hypothyroidism was independently associated with increased all-cause mortality in older adults. In patients with hypothyroidism, TRT was associated with a lower risk of all-cause mortality.

Context: Approximately 60% to 80% of patients with congenital central hypothyroidism (CH-C) have multiple pituitary hormone deficiencies (MPHDs), making CH-C a potentially life-threatening disease. Data on mortality in patients with CH-C are lacking., Objective: To study the mortality rate in pediatric patients with early-detected and treated CH-C in the Netherlands and to investigate whether causes of death were related to pituitary hormone deficiencies., Methods: Overall mortality rate, infant mortality rate (IMR), and under-5 mortality rate were calculated in all children with CH-C detected by neonatal screening between 1 January 1995 and 1 January 2013. Medical charts were reviewed to establish causes of death., Results: A total of 139 children with CH-C were identified, of which 138 could be traced (82 with MPHD, 56 with isolated CH-C). Total observation time was 1414 years with a median follow-up duration of 10.2 years. The overall mortality rate was 10.9% (15/138). IMR and under-5 mortality rate were 65.2/1000 (9/138) and 101.4/1000 (14/138), respectively, compared with an IMR of 4.7/1000 and under-5 mortality of 5.4/1000 live-born children in the Netherlands during the same time period (P < 0.0001). Main causes of death were severe congenital malformations in six patients, asphyxia in two patients, and congenital or early neonatal infection in two patients. Pituitary hormone deficiency was noted as cause of death in only one infant., Conclusion: We report an increased mortality rate in patients with early-detected CH-C that does not seem to be related to endocrine disease. This suggests that mortality due to pituitary insufficiency is low in patients with early-detected and early-treated CH-C.

Aim: The prevalence of hypothyroidism is high in haemodialysis (HD) patients and hypothyroidism increases all-cause mortality in HD patients. Comorbidities are common in HD patients and are associated with both mortality and hypothyroidism. The aim of the study is to explore the effect of the interactions of comorbidities and hypothyroidism on all-cause mortality in HD patients., Method: Patients with hypothyroidism (ICD-9-CM 244.0, 244.1, and 244.9) and matched patients without hypothyroidism in the Registry for Catastrophic Illness Patient Database of Taiwan Health Insurance from 2000 to 2010 were analyzed. The association of hypothyroidism and risk of all-cause mortality was analyzed using Cox proportional hazard regression., Result: Nine hundred and eight HD patients with hypothyroidism and 3632 sex-, age-, gender- matched HD patients without hypothyroidism were analyzed. Hypothyroidism was associated with increased all-cause mortality with an adjusted hazard ratio of 1.22 [95% confidence interval (CI): 1.10-1.36, P < 0.001]. TRT may decrease mortality associated with hypothyroidism (P < 0.001). There was a significant interaction (P = 0.04) between diabetes and hypothyroidism. There was no significant interaction found in hypothyroidism and the following comorbidities: hyperlipidaemia, hypertension, chronic obstructive pulmonary disease, coronary artery disease, stroke, peripheral arterial disease, asthma, congestive heart failure and cancer., Conclusion: Hypothyroidism is associated with increased all-cause mortality in chronic HD patients. The interaction of hypothyroidism and diabetes, but not other common comorbidities in HD patients, has an effect on mortality risks., (© 2017 Asian Pacific Society of Nephrology.)

Objective: Given that patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) have a disproportionately higher prevalence of hypothyroidism compared with their non-CKD counterparts, we sought to determine the association between thyroid status, defined by serum thyrotropin (TSH) levels, and mortality among a national cohort of patients with NDD-CKD., Patients and Methods: Among 227,422 US veterans with stage 3 NDD-CKD with 1 or more TSH measurements during the period October 1, 2004, to September 30, 2012, we first examined the association of thyroid status, defined by TSH categories of less than 0.5, 0.5 to 5.0 (euthyroidism), and more than 5.0 mIU/L, with all-cause mortality. We then evaluated 6 granular TSH categories: less than 0.1, 0.1 to less than 0.5, 0.5 to less than 3.0, 3.0 to 5.0, more than 5.0 to 10.0, and more than 10.0 mIU/L. We concurrently examined thyroid status, thyroid-modulating therapy, and mortality in sensitivity analyses., Results: In expanded case-mix adjusted Cox analyses, compared with euthyroidism, baseline and time-dependent TSH levels of more than 5.0 mIU/L were associated with higher mortality (adjusted hazard ratios [aHRs] [95% CI], 1.19 [1.15-1.24] and 1.23 [1.19-1.28], respectively), as were baseline and time-dependent TSH levels of less than 0.5 mIU/L (aHRs [95% CI], 1.18 [1.15-1.22] and 1.41 [1.37-1.45], respectively). Granular examination of thyroid status showed that incrementally higher TSH levels of 3.0 mIU/L or more were associated with increasingly higher mortality in baseline and time-dependent analyses, and TSH categories of less than 0.5 mIU/L were associated with higher mortality (reference, 0.5-<3.0 mIU/L) in baseline analyses. In time-dependent analyses, untreated and undertreated hypothyroidism and untreated hyperthyroidism were associated with higher mortality (reference, spontaneous euthyroidism), whereas hypothyroidism treated-to-target showed lower mortality., Conclusion: Among US veterans with NDD-CKD, high-normal TSH (≥3.0 mIU/L) and lower TSH (<0.5 mIU/L) levels were associated with higher death risk. Interventional studies identifying the target TSH range associated with the greatest survival in patients with NDD-CKD are warranted., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: This study investigated the association between hypothyroidism and mortality in both treated and untreated hypothyroid patients, and the consequences of over- and under-treatment with respect to mortality., Patients and Methods: This was a register-based cohort study of 235,168 individuals who had at least one serum thyrotropin (TSH) during 1995-2011 (median follow-up 7.2 years). Hypothyroidism was defined as at least two measurements of TSH >4.0 mIU/L within a half year spaced by at least 14 days, or one measurement of TSH >4.0 mIU/L and two filled prescriptions of levothyroxine the following year. All-cause mortality rates were calculated using multivariable Cox regression analysis adjusted for age, sex, and comorbidities using the Charlson Comorbidity Index., Results: Mortality was increased in untreated hypothyroid individuals (n = 673; hazard ratio [HR] = 1.46 [confidence interval (CI) 1.26-1.69]; p < 0.001) compared to euthyroid controls. Results remained significant even when subdividing according to mild (TSH >4.0 mIU/L and ≤10 mIU/L; p < 0.001) and marked hypothyroidism (TSH >10 mIU/L; p = 0.002). Mortality was increased in both treated and untreated hypothyroid individuals for each six months a patient had increased TSH (HR = 1.05 [CI 1.02-1.07], p < 0.0001, and HR = 1.05 [CI 1.02-1.07], p = 0.0009, respectively). In patients who received levothyroxine, the HR for mortality increased by a factor 1.18 ([CI 1.15-1.21]; p < 0.0001) for each six months a patient exhibited decreased TSH. This finding was essentially unchanged after stratification by disease severity (mild or marked hypothyroidism) and age (older and younger than 65 years)., Conclusions: Mortality was increased in untreated but not in treated hypothyroid individuals, independently of age and severity of hypothyroidism. Duration of decreased TSH in treated individuals had a greater impact on mortality than did duration of elevated TSH. These results stress the need for close monitoring of treatment in individuals receiving thyroid hormone replacement therapy.

Background: Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction is recognized as a common adverse effect of treatment, but the importance of incident hypothyroidism during TKI therapy remains unclear. This study analyzed the prognostic significance of hypothyroidism during TKI therapy in cancer patients., Methods: This was a retrospective cohort study of adult patients with advanced nonthyroidal cancer treated with TKI and available thyroid function testing at three affiliated academic hospitals from 2000 to 2017. Patients with preexisting thyroid disease were excluded. Demographic, clinical, and cancer treatment data were collected. Thyroid status with TKI treatment was determined from thyroid function testing and initiation of thyroid medication, and classified as euthyroid (thyrotropin [TSH] normal), subclinical hypothyroidism (SCH; TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (OH; TSH >10 mIU/L, low free thyroxine, or requiring replacement). Multivariate models were used to evaluate the effect of TKI-related hypothyroidism on overall survival (OS)., Results: Of 1120 initial patients, 538 remained after exclusion criteria. SCH occurred in 72 (13%) and OH in 144 (27%) patients with TKI therapy. Patients with hypothyroidism had significantly longer OS, with median OS in euthyroid patients of 685 days [confidence interval (CI) 523-851] compared to 1005 days [CI 634-1528] in SCH and 1643 days [CI 1215-1991] in OH patients (p < 0.0001). After adjustment for age, sex, race/ethnicity, cancer type, cancer stage, ECOG performance status, and checkpoint inhibitor therapy, OH remained significantly associated with OS (hazard ratio = 0.561; p < 0.0001), whereas SCH did not (hazard ratio = 0.796; p = 0.165). Analysis of hypothyroid patients (SCH and OH) with TSH >5 and <10 mIU/L stratified by hormone replacement status showed improved survival associated with hormone replacement., Conclusions: New hypothyroidism in cancer patients treated with TKI is associated with significantly improved OS, should not necessitate TKI dose reduction or discontinuation, and may provide independent prognostic information.

Introduction: It is uncertain whether subclinical hypothyroidism should be treated with levothyroxine, particularly in the elderly. This study evaluated the association between levothyroxine treatment and mortality in individuals 65years or older with subclinical hypothyroidism and TSH values <10mIU/L., Methods: A case-control study in which patients 65years or older with TSH levels of 4.2-10mIU/L who died in the years 2012-2016 ('cases') were compared with matched individuals who did not die during this period ('controls'). Matching was based on gender, age, Charlson comorbidity index, date of TSH testing, duration of follow-up and TSH quartile. All cases of known thyroid disease or cases in which anti-thyroid medications or glucocorticoids were dispensed in the year preceding the TSH evaluation were excluded. Use of levothyroxine was compared between groups., Results: During the follow-up period, 419 individuals died and these were matched with 1558 individuals who did not. Factors found to be associated with mortality were age, senile dementia, congestive heart failure, chronic renal failure and a history of cerebrovascular disease. On multivariate analysis, treatment with levothyroxine was associated with significantly increased mortality (HR=1.19 CI 1.03-1.38). Femoral fractures and atrial fibrillation following initiation of levothyroxine therapy were not more prevalent in individuals who died during the follow-up period., Conclusions: Treatment with levothyroxine is associated with significantly increased mortality in individuals 65years or older with subclinical hypothyroidism and TSH<10., (Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Similar to overt hypothyroidism, subclinical hypothyroidism (SCH) has been reported to increase the risk of cardiovascular disease. However, the influence of SCH on clinical outcomes following percutaneous coronary intervention (PCI) remains unclear., Methods: We performed a prospective cohort study. SCH was defined as a thyroid-stimulating hormone (TSH) level ≥4.5mIU/l and a normal level of free thyroxine (FT4). A composite event was defined as the combination of cardiac death, non-fatal myocardial infarction (MI) and repeat revascularization., Results: Of 936 patients, who were observed for 3.1years, 100 patients (10.7%) were diagnosed with SCH. Repeat revascularization, cardiac death and a composite event occurred more frequently in the SCH group than in the euthyroidism group, while the incidence of non-fatal MI was similar between the two groups. Multiple Cox regression analysis showed that SCH was associated with the risk of a composite event (hazard ratio, 1.52; 95% confidence interval, 1.04-2.22) after adjustment for age, sex, current smoking, ST-segment elevation MI, prior PCI, diabetes, hypertension, renal function, left ventricular ejection fraction, B-type natriuretic peptide, stent numbers, total stent length, stent types, obesity and lipid profiles. Serum TSH levels were also significantly associated with the risk of a composite event. SCH was not associated with repeat PCIs for de novo stenotic lesions but was associated with repeated PCIs for in-stent restenotic lesions., Conclusions: SCH negatively impacted clinical outcomes following PCIs. Therefore, patients with SCH should be carefully observed after undergoing a PCI., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Suggested strategies in reducing the impact of non-communicable diseases (NCD) are early diagnosing and screening. We have limited proof of benefit of population screening for NCD. Increased mortality in persons with diagnosed NCD has been shown for decades. However, mortality in undetected NCD has barely been studied. This paper explores whether all-cause mortality differed between persons with diagnosed hypothyroidism, type 2 diabetes (T2DM), and hypertension, compared with persons with undetected-, and with persons without the corresponding disease., Methods: A prospective cohort study of the general population in Nord-Trøndelag, Norway. Persons ≥20 years at baseline 1995-97 were followed until death or June 15, 2016. Cox proportional hazards models were used to compute age and multiple adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association between disease status and all-cause mortality. The number of participants in the hypothyroidism study was 31,960, in the T2DM study 37,957, and in the hypertension study 63,371., Results: Mortality was increased in persons with diagnosed type 2 diabetes and hypertension, compared to persons without corresponding disease; HR 1.69 (95% CI 1.55-1.84) and HR 1.23 (95% CI 1.09-1.39), respectively. Among persons with undetected T2DM, the HR was 1.21 (95% CI 1.08-1.37), whilst among undetected hypothyroidism and hypertension, mortality was not increased compared with persons without the diseases. Further, the association with mortality was stronger in persons with long duration of T2DM (HR 1.96 (95% CI 1.57-2.44)) and hypertension (HR 1.32 (95% CI 1.17-1.49)), compared with persons with short duration (HR 1.29 (1.09-1.53) and HR 1.16 (1.03-1-30) respectively)., Conclusions: Mortality was increased in persons with diagnosed T2DM and hypertension, and in undetected T2DM, compared with persons without the diseases. The strength of the association with mortality in undetected T2DM was however lower compared with persons with diagnosed T2DM, and mortality was not increased in persons with undetected hypothyroidism and hypertension, compared with persons without the diseases. Thus, future research needs to test more thoroughly if early diagnosing of these diseases, such as general population screening, is beneficial for health.

Purpose: Overt hypothyroidism has adverse clinical consequences and might worsen prognosis in critically ill elderly patients. However, the difficult interpretation of thyroid function tests (TFT) due to non-thyroidal illness (NTI) has led to discouragement of screening for thyroid dysfunction. Our aim was to determine the prevalence of TFT compatible with hypothyroidism and to study its influence on mortality among hospitalized elderly patients., Methods: In this prospective study we consecutively included all patients ≥60 years admitted by the Internal Medicine Department to the hospital ward (n = 451) of the Cesar Milstein Hospital in Buenos Aires, Argentina. TFT were done on day 1 and 8. Thyroid function categories were defined as overt and subclinical hypothyroidism, overt and subclinical hyperthyroidism, euthyroidism and NTI. Stage of chronic kidney disease (CKD), Adult Comorbidity Evaluation (ACE)-27, and intra-hospital mortality were recorded. The association between mortality and TFT categories was studied by Cox regression., Results: Out of 451 patients (77.0 ± 7.9 years, 54% females) 76% were categorized as NTI, 4% as overt hypothyroid, 10% as subclinical hypothyroid, 1% as subclinical hyperthyroid and 9% as euthyroid. Overt hypothyroid patients showed significantly higher mortality than the rest of the groups (25%, p < 0.05) while ACE-27 was similar among all of them (p = 0.658). In addition, patients within the overt hypothyroid category showed a higher mortality rate than NTI in a model adjusted by Stage 5-CKD, ACE-27, sex and age [HR 3.1 (1.14-8.41), p < 0.026]., Conclusion: Overt hypothyroidism during hospitalization was associated with elevated mortality. Further studies would reveal if TFT alterations compatible with hypothyroidism should be diagnosed/treated in hospitalized elderly patients.

Context: Limited data is available regarding the association between pre-admission thyroid function and prognosis of hospitalized patients treated for hypothyroidism., Objective: Evaluate an association between thyroid stimulating hormone (TSH) levels and mortality in hospitalized levothyroxine-treated patients., Design and Setting: Observational data of patients admitted to medical wards between 2011 and 2013. TSH levels obtained up to 180 days prior to admission were stratified as follows: low (≤0.5 mIU/L), normal (0.5-5 mIU/L), high (>5 mIU/L)., Patients: Patients aged 60-80 years with available thyroid function tests were matched with controls without hypothyroidism., Main Outcome: All-cause mortality up to 66-months following discharge., Results: One thousand and fifty seven patients (73% females, mean (SD) age 71 ± 6 years) were matched with controls without hypothyroidism. Mean hospital stay and in-hospital mortality were not different between groups. Mortality risk at the end-of-follow-up was 41% (438/1057) and 37% (392/1057) for patients with and without hypothyroidism (p < 0.05). TSH levels were classified as follows: low, 84 patients (8%); normal, 667 patients (63%); high, 306 patients (29%). Length of hospitalization and in-hospital mortality were not different between TSH categories. Mortality risk at the end-of-follow-up was 30, 39, and 50% with low, normal and elevated TSH, respectively. Adjusted hazard ratio (95% CI) of mortality at the end-of-follow-up was of 2.2 (1.2-3.8) for high vs. low TSH levels, and 1.4 (1.1-1.9) for high vs. normal TSH levels., Conclusion: In treated hypothyroid adult patients, increased TSH up to 6 months prior to admission is associated with increased mortality. Treatment should aim at achieving euthyroidism to improve survival.

The number of elderly people, mostly aged over 85 years (the 'oldest old'), is increasing worldwide. As a consequence, accompanying morbidity and disability have been increasing, and frailty, defined as an age-related condition of decline of physiological reserves and vulnerability, represents an emerging problem. Caring for older frail people may represent a challenge, since the elderly differ significantly from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions. Specific criteria of therapeutic appropriateness and modified goals of care are needed in such patients, also in endocrine care settings. Indeed, thyroid dysfunctions are among the most common conditions in older, multimorbid populations. The prevalence of overt and subclinical hypothyroidism is as high as 20% and thyroid hormone prescription is common in the elderly, with a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism. In addition, older patients have the highest rate of overtreatment during replacement therapy and are more susceptible to developing adverse effects from thyroid hormone excess. Recently, results of a multicentric randomized controlled trial, the TRUST-IEMO collaboration trial, added further insights to the debated question of whether and when levothyroxine treatment is required and if it is beneficial in the elderly. With this in mind, we revised the relevant literature on the impact of thyroid dysfunction and replacement therapy among older people, with the aim to better define indications, benefits and risks of l-T4 replacement therapy in the frail elderly., (© 2017 European Society of Endocrinology.)

Context: Numerous studies investigated the link between hypothyroidism and mortality, but a definite conclusion is hard to reach as these were limited by a number of factors, including age of participants, comorbidities and single measurement of thyroid function., Objective: To evaluate the association between TSH and fT4 levels and mortality in patients with levothyroxine-treated hypothyroidism., Design and Setting: Observational data of hospitalized patients (2011-2014). TSH and fT4 levels obtained between at least 30 days after discharge and until death or end of follow-up were collected. Median TSH and fT4 levels were stratified into categories., Patients: In total, 611 patients with treated hypothyroidism, aged 60-80 years (72% females, mean age 71 ± 6 years) were included in the study., Main Outcome Measure: All-cause mortality up to 66 months after discharge, by TSH and fT4 categories., Results: During follow-up, the average numbers of TSH and fT4 measurements were 5.5 ± 3.8 and 2.5 ± 4.2 per patient respectively. Mortality rates were 28%, 29% and 54% with median TSH of 0.5-2.5, 2.5-5.0 and 5.0-10.0 IU/L respectively. Adjusted hazard ratios for mortality with median TSH between 5.0 and 10.0 IU/L were 2.3 (95% CI: 1.6-3.4) and 2.2 (95% CI: 1.6-3.2) compared with patients with TSH between 0.5-2.5 IU/L and 2.5-5 IU/L respectively. There was no difference in mortality between patients with median fT4 10-15 or 15-20 pmol/L., Conclusion: In treated hypothyroid adult patients and serial measurements of thyroid function tests, median TSH levels of 5-10 IU/L are associated with increased mortality with no effect of fT4 levels. Treatment should aim at achieving euthyroidism to improve survival., (© 2017 European Society of Endocrinology.)

Background/aims: Thyroid disease is a common comorbidity in individuals with Down syndrome (DS), but historical studies have multiple limitations. We assessed thyroid abnormalities in a large cohort of children with DS., Methods: Retrospective records review from a single institution. Calculated prevalence of common thyroid abnormalities and associations with common comorbidities., Results: Among 508 patients, 120 (24%) had a thyroid-related diagnosis, the majority having elevated thyrotropin treated with levothyroxine. A Kaplan-Meier estimate projects that 50% have thyroid disorder by adulthood, with 20% of hypothyroidism diagnosed before the age of 6 months. When tested, approximately 50% had positive antithyroid antibodies, though this rate was 100% in overt hypothyroidism. There was no association between congenital or acquired hypothyroidism and common comorbidities., Conclusion: Thyroid disease in DS is more common and occurs earlier than in the general population, and is often transient. Thyroid disease is unrelated to gender, obesity, or other comorbidities. Apart from overt hypothyroidism, much of hypothyroidism in DS appears unrelated to autoimmunity; we recommend checking of antithyroid antibodies only in select cases. An additional screen for thyroid disease between the newborn screen and the 6-month well-child visit will detect early cases of hypothyroidism who passed their newborn screen.
., (© 2017 S. Karger AG, Basel.)

Context and Objective: End-stage renal disease patients have a higher risk of thyroid disease compared with those without kidney disease. Although thyroid dysfunction is associated with higher death risk in the general population and those undergoing hemodialysis, little is known about the effect of thyroid disease upon mortality in patients treated with peritoneal dialysis (PD)., Design, Setting, Participants, and Main Outcome: We examined the association of thyroid status, assessed by serum TSH, with all-cause mortality among PD patients from a large national dialysis organization who underwent one or more TSH measurements over 5 years (January 2007 to December 2011). Thyroid status was categorized as overt-hyperthyroid, subclinical-hyperthyroid, low-normal, high-normal, subclinical-hypothyroid, and overt-hypothyroid range (TSH < 0.1, 0.1–<0.5, 0.5–<3.0, 3.0–<5.0, 5.0–<10.0, and ≥10.0 mIU/L, respectively). We examined the association between TSH and mortality using case mix–adjusted time-dependent Cox models to assess short-term thyroid function–mortality associations and to account for changes in thyroid function over time., Results: Among 1484 patients, 7 and 18% had hyperthyroidism and hypothyroidism, respectively, at baseline. We found that both lower and higher time-dependent TSH levels were associated with higher mortality (reference: TSH, 0.5-<3.0 mIU/L): adjusted hazard ratios (95% confidence intervals) 2.09 (1.08-4.06), 1.53 (0.87-2.70), 1.05 (0.75-1.46), 1.63 (1.11-2.40), and 3.11 (2.08-4.63) for TSH levels, <0.1, 0.1-<0.5, 0.5-<3.0, 3.0-<5.0, 5.0-<10.0, and ≥10.0 mIU/L, respectively., Conclusion: Time-dependent TSH levels < 0.1 mIU/L and ≥ 5.0 mIU/L were associated with higher mortality, suggesting hyper- and hypothyroidism carry short-term risk in PD patients. Additional studies are needed to determine mechanisms underlying the thyroid dysfunction-mortality association, and whether normalization of TSH with treatment ameliorates mortality in this population.

Background: Low thyroid function within the euthyroid range, as well as overt and subclinical hypothyroidism, reportedly increases the risk of cardiovascular disease and mortality. However, the association between low normal thyroid function and mortality remains controversial. This study was performed to elucidate the association between low normal thyroid function and all-cause and/or cause-specific mortalities among U.S. adults., Methods: A prospective cohort study was conducted using a nationally representative sample of 12,584 U.S. adults aged ≥20 years with thyrotropin (TSH) levels within the reference range from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Associations between TSH tertiles (high, medium, and low normal TSH groups) and mortalities (all-cause, cardiovascular, and cancer) were investigated using multivariable Cox models. Stratum-specific analyses were estimated within subgroups defined according to sex (male or female) and baseline age (age <60 years or age ≥60 years). Further, the same analysis was conducted using continuous NHANES 2001-2002, 2007-2008, and 2009-2010 cohorts, which included data on free thyroxine levels., Results: The median follow-up period was 19.1 years, with 3395 all-cause deaths. A significantly higher risk of all-cause mortality (adjusted hazard ratio [HR] 1.27; [confidence interval (CI) 1.10-1.47]), and cardiovascular mortality (HR 1.30 [CI 1.02-1.67]), and cancer mortality (HR 1.43 [CI 1.01-2.01]) was observed in the high normal TSH group than in the medium normal TSH group. Additionally, the low normal TSH group had an increased risk of all-cause mortality. In stratum-specific analyses, a significant association was found between high normal TSH levels and all-cause mortality among males, females, and participants <60 years. Continuous NHANES cohorts demonstrated a non-significant increase in the HR for all-cause mortality in the high normal TSH group., Conclusions: High normal TSH levels compared with medium normal TSH levels were associated with increased risk of all-cause, cardiovascular, and cancer mortalities over a long-term follow-up period among U.S. adults. This study indicates that the reference range for TSH levels may require re-evaluation.

Purpose: In childhood cancer survivors, the most common late effect is thyroid dysfunction, most notably subclinical hypothyroidism (SCH). Our study evaluated the risk factors for persistent SCH in survivors., Materials and Methods: Survivors (n=423) were defined as patients who survived at least 2 years after cancer treatment completion. Thyroid function was assessed at this time and several years thereafter. Two groups of survivors with SCH were compared: those who regained normal thyroid function during the follow-up period (normalized group) and those who did not (persistent group)., Results: Overall, 104 of the 423 survivors had SCH. SCH was observed in 26% of brain or nasopharyngeal cancer survivors (11 of 43) and 21.6% of leukemia survivors (35 of 162). Sixty-two survivors regained normal thyroid function, 30 remained as persistent SCH, and 12 were lost to follow-up. The follow-up duration was 4.03 (2.15-5.78) years. Brain or nasopharyngeal cancer and Hodgkin disease were more common in the persistent group than in the normalized group (p=0.002). More patients in the persistent group received radiation (p=0.008). Radiation to the head region was higher in this group (2394±2469 cGy) than in the normalized group (894±1591 cGy; p=0.003). On multivariable analysis, lymphoma (p=0.011), brain or nasopharyngeal cancer (p=0.039), and head radiation dose ≥1800 cGy (p=0.039) were significant risk factors for persistent SCH., Conclusion: SCH was common in childhood cancer survivors. Brain or nasopharyngeal cancer, lymphoma, and head radiation ≥1800 cGy were significant risk factors for persistent SCH.

Objective: The association between subclinical hypothyroidism and hyperthyroidism and mortality in the elderly is poorly defined. This study was designed to evaluate the association between subclinical hypothyroidism and subclinical hyperthyroidism and mortality in the elderly and to define the thyroid-stimulating hormone values associated with excess mortality in the elderly., Methods: We performed a retrospective cohort study with a review of a computerized database of a large health care organization. Patients aged more than 65 years evaluated in the years 2002 to 2012 with documented normal free T4 values were included in the analysis. All cases of known thyroid disease or cases in which thyroid medications were dispensed were excluded. Analysis was performed only on individuals who were not treated for hyperthyroidism or hypothyroidism during the follow-up period. Subjects were divided into 3 groups based on thyroid-stimulating hormone values: normal (normal thyroid-stimulating hormone), subclinical hypothyroidism (thyroid-stimulating hormone >4.2 mIU/L), and subclinical hyperthyroidism (thyroid-stimulating hormone <0.35 mIU/L). All-cause mortality hazard ratio (HR) was compared among the 3 groups, and a subanalysis according to thyroid-stimulating hormone values was performed in those with subclinical hypothyroidism and subclinical hyperthyroidism., Results: A final analysis was performed on 17,440 individuals with subclinical thyroid disease (538 with subclinical hyperthyroidism [3.1%], 1956 with subclinical hypothyroidism [11.2%], 14,946 normal cases [85.7%], average age of 83 years, 10,289 were women) who were followed up for 10 years. Both subclinical hypothyroidism (HR, 1.75; confidence interval [CI], 1.63-1.88) and subclinical hyperthyroidism (HR, 2.33; CI, 2.08-2.63) were associated with significantly increased mortality, and this association persisted on multivariate analysis (subclinical hypothyroidism HR, 1.68; CI, 1.56-1.8, subclinical hyperthyroidism HR, 1.93; CI, 1.7-2.17). Crude mortality was elevated at 1, 2, and 5 years, but this association seemed to decrease as time from initial analysis increased (most significant association at 1 year). Thyroid-stimulating hormone values greater than 6.38 mIU/L were associated with the highest mortality in those with subclinical hypothyroidism after multivariate adjustment (HR, 1.708; CI, 1.38-2.12), whereas in subclinical hyperthyroidism, no threshold for increased mortality was identified. Mortality was higher., Conclusions: Both subclinical hypothyroidism and subclinical hyperthyroidism are associated with increased mortality in the elderly. A threshold thyroid-stimulating hormone value (>6.35 mIU/L) exists for increased mortality in subclinical hypothyroidism, but not in subclinical hyperthyroidism., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Clinical implications of subclinical hypothyroidism (SCH) are still matter of intense debate, resulting in the controversial discussion whether subclinical hypothyroidism should be treated. We performed a cohort study to evaluate the impact of subclinical hypothyroidism on vascular and overall mortality., Methods: Between 02/1993 and 03/2004, a total of 103,135 persons attending the General Hospital Vienna with baseline serum thyrotropin (TSH, thyroid-stimulating hormone) and free thyroxin (fT4) measurements could be enrolled in a retrospective cohort study. Subclinical hypothyroidism was defined by elevated TSH ranging from 4.5 to 20.0 mIU/L and normal fT4 concentration (0.7-1.7 ng/dL). Overall and vascular mortality as primary endpoints were assessed via record linkage with the Austrian Death Registry., Results: A total of 80,490 subjects fulfilled inclusion criteria of whom 3934 participants (3.7%) were classified as SCH (868 males and 3066 females, median age 48 years). The mean follow-up among the 80,490 subjects was 4.1 years yielding an observation period of 373,301 person-years at risk. In a multivariate Cox regression model adjusted for age and gender TSH levels showed a dose-dependent association with all-cause mortality. The association between SCH and overall or vascular mortality was stronger in men below 60 years compared to older males or females., Conclusion: Our data support the hypothesis that SCH might represent an independent risk factor for overall and vascular mortality, especially in men below 60 years. Whether this group would benefit from replacement therapy should be evaluated in interventional studies.

Background: We tested the hypothesis that hypothyroidism, as defined by thyroid-stimulating hormone (TSH) concentration, is associated with a severity-weighted composite of mortality and major cardiovascular and infectious complications after noncardiac surgery., Methods: In this retrospective cohort study, we evaluated adults at the Cleveland Clinic Main Campus between 2005 and 2012, who had had available TSH concentrations within the 6 months before noncardiac surgery. Patients were categorized as (1) hypothyroid (patients who had diagnosis of hypothyroidism any time prior to surgery and increased TSH value (> 5.5 mIU/L) within 6 months prior to surgery); (2) treated (hypothyroid diagnosis and normal TSH concentrations [0.4-5.5 mIU/L]); and (3) euthyroid (no hypothyroid diagnosis and normal TSH concentrations). We conducted pairwise comparisons among the 3 groups using inverse propensity score weighting to control for observed confounding variables. Average relative effect generalized estimating equation model was used for the primary outcome composite of in-hospital cardiovascular morbidity, surgical wound complication or infection, and mortality. Logistic regression and Cox proportional hazards regression were used for secondary outcomes of intraoperative vasopressor use and duration of hospitalization, respectively., Results: We identified 800 hypothyroid patients (median TSH: 8.6 mIU/L [Q1, Q3: 6.5, 13.0]), 1805 treated patients (2.0 mIU/L [1.1, 3.2]), and 5612 euthyroid patients (1.7 mIU/L [1.1, 2.6]). There were no significant differences among the hypothyroid, treated, and euthyroid patients on the primary composite outcome (all P values ≥0.30). Hypothyroid patients were slightly more likely to receive vasopressor during surgery than either treated (odds ratio, 1.17; 99.2% confidence interval [CI], 1.01-1.36) or euthyroid (odds ratio, 1.12; 99.2% CI, 1.02-1.24) patients. Furthermore, hypothyroid patients were slightly but significantly less likely to be discharged at any given postoperative time than treated patients (hazard ratio, 0.92; 99.2% CI, 0.86-0.99)., Conclusions: Hypothyroidism was not associated with worse postoperative mortality, wound, or cardiovascular outcomes in noncardiac patients. Thus, postponing surgery to initiate thyroid replacement therapy in patients with hypothyroidism seems unnecessary.

Background: Down syndrome is a genetic condition that contributes to a significantly shorter life expectancy compared with the general population. We investigated the most common comorbidities in a population of acute hospital patients with Down syndrome and further explored what the most common risk factors for mortality are within this population., Method: From our database of one million patients admitted to National Health Service (NHS) Trusts in northern England, we identified 558 people who had Down syndrome. We compared this group with an age- and gender-matched control group of 5580 people., Results: The most prevalent comorbid diseases within the Down's population were hypothyroidism (22.9%) and epilepsy (20.3%). However, the conditions that had the highest relative risks (RRs) in the Down's population were septal defects and dementia. Respiratory failure, dementia and pneumonia were the most significantly related comorbidities to mortality in the Down syndrome population. In the control population, respiratory failure, dementia and renal failure were the most significant disease contributors. When these contributors were analysed using multivariate analysis, heart failure, respiratory failure, pneumonia and epilepsy were the identified risk factors for in-hospital mortality in the Down syndrome population. Respiratory failure was the sole risk factor for mortality in the Down syndrome population [RR = 9.791 (1.6-59.9) P ≤ 0.05], when compared with the risk factors for mortality in the control population., Conclusions: There is significant medical morbidity in Down syndrome. This morbidity contributes to the lower life expectancy. Respiratory failure is a risk factor for mortality in Down syndrome. We need to thoroughly investigate people with Down syndrome to ensure any treatable illnesses are well managed., (© 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Background and Objectives: A direct association between low triiodothyronine (T3) syndrome and cardiovascular (CV) mortality has been reported in hemodialysis patients. However, the implications of this syndrome in peritoneal dialysis (PD) patients have not been properly investigated. This study examined the association between low T3 syndrome and CV mortality including sudden death in a large cohort of incident PD patients., Design, Setting, Participants, & Measurements: This prospective observational study included 447 euthyroid patients who started PD between January 2000 and December 2009. Measurement of thyroid hormones was performed at baseline. All-cause and cause-specific deaths were registered during the median 46 months of follow-up. The survival rate was compared among three groups based on tertile of T3 levels., Results: In Kaplan-Meyer analysis, patients with the lowest tertile were significantly associated with higher risk of all-cause and CV mortality including sudden death (P<0.001 for trend). In Cox analyses, T3 level was a significant predictor of all-cause mortality (per 10-unit increase, adjusted hazard ratio [HR], 0.86; 95% confidence interval [95% CI], 0.78 to 0.94; P=0.002), CV death (per 10-unit increase, adjusted HR, 0.84; 95% CI, 0.75 to 0.98; P=0.01), and sudden death (per 10-unit increase, adjusted HR, 0.69; 95% CI, 0.56 to 0.86; P=0.001) after adjusting for well known risk factors including inflammation and malnutrition. The higher T3 level was also independently associated with lower risk for sudden death (per 10-unit increase, adjusted HR, 0.71; 95% CI, 0.56 to 0.90; P=0.01) even when accounting for competing risks of death from other causes., Conclusions: T3 level at the initiation of PD was a strong independent predictor of long-term CV mortality, particularly sudden death, even after adjusting well known risk factors. Low T3 syndrome might represent a factor directly implicated in cardiac complications in PD patients., (Copyright © 2015 by the American Society of Nephrology.)

Context: Arrhythmia is a major cause of morbidity and mortality in Europe and in the United States. The aim of this review article was to assess the results of the prospective studies that evaluated the risk of arrhythmia in patients with overt and subclinical thyroid disease and discuss the management of this arrhythmia., Evidence Acquisition: A literature search was carried out for reports published with the following terms: thyroid, hypothyroidism, hyperthyroidism, subclinical hyperthyroidism, subclinical hypothyroidism, levothyroxine, triiodothyronine, antithyroid drugs, radioiodine, deiodinase, atrial flutter, supraventricular arrhythmia, ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation, torsade de pointes, amiodarone and atrial fibrillation. The investigation was restricted to reports published in English., Evidence Analysis: The outcome of this analysis suggests that patients with untreated overt clinical or subclinical thyroid dysfunction are at increased risk of arrhythmia. Hyperthyroidism increased atrial arrhythmia; however, hypothyroidism increased ventricular arrhythmia., Conclusion: The early recognition and effective treatment of thyroid dysfunction in patients with arrhythmia is mandatory because the long-term prognosis of arrhythmia may be improved with the appropriate treatment of thyroid dysfunction.