Project description:Subclinical hypothyroidism (SCH) is a common disorder that is characterized by elevated thyroid-stimulating hormone levels in conjunction with free thyroxine concentrations within the normal reference range. Thyroid hormones are known to affect the heart and vasculature and, as a result, the impact of SCH on the cardiovascular (CV) system has recently become an important topic of research. Strong evidence points to a link between SCH and CV risk factors such as alterations in blood pressure, lipid levels, and atherosclerosis. Additionally, accumulating evidence indicates that SCH is associated with metabolic syndrome and heart failure. The present review proposes that SCH may be a potentially modifiable risk factor of CV disease and mortality. However, large-scale clinical trials with appropriate power investigating the risks and benefits of SCH treatment are required to determine whether these benefits can be achieved with levothyroxine therapy.
Project description:Subclinical hypothyroidism (SH) is a common condition, with prevalence estimates ranging from 4-20%, depending on the population demographics. Although epidemiological analysis associates it with an increased risk of cardiovascular disease, clinical practice guidelines express uncertainty about whether to monitor or to treat. As we await large-scale, well-designed randomised clinical trials regarding treatment of SH, a review of pathophysiological considerations may be informative to better understand this disorder.
Project description:Objectives. To evaluate the effect of levothyroxine (LT4) replacement therapy on nonalcoholic fatty liver disease (NAFLD) in subclinical hypothyroidism (SCH) patients. Methods. This study was a post hoc analysis of a randomized controlled trial and involved 33 significant and 330 mild SCH patients. All of the significant SCH patients received LT4 supplement. The mild SCH patients were grouped as LT4 treated or not. After 15 months of follow-up, prevalence of NAFLD in each group was reevaluated. Subgroup analysis was conducted in mild SCH patients with dyslipidemia. Results. After treatment with LT4, the prevalence of NAFLD in significant SCH patients reduced from 48.5% to 24.2% (p = 0.041). In mild SCH patients, prevalence of NAFLD and serum alanine aminotransferase (ALT) was not significantly affected by LT4 supplementation. Nonetheless, mild SCH patients with dyslipidemia who received LT4 treatment experienced decreases in the prevalence of NAFLD and serum ALT levels (p < 0.05 for both). In contrast, these parameters remained comparably stable in patients who were not treated. Conclusion. LT4 supplementation has benefits on NAFLD in significant SCH patients or mild SCH patients with dyslipidemia. For NAFLD patients with SCH, appropriate supplementation of LT4 may be an effective means of controlling NAFLD. The original trial was registered with ClinicalTrials.gov (NCT01848171).
Project description:levothyroxine prescriptions have increased remarkably during the last decade, and it is most likely to be prescribed in subclinical hypothyroidism. The aim of this review was to present data on when levothyroxine treatment should be initiated, and the effects of treatment in subclinical hypothyroidism on symptoms such as weight, quality of life, vitality, cognition, and cardiovascular disease. We also discuss evidence for different thyroid-hormone medications. In addition, the option to withhold medication when there is uncertain diagnosis or lack of clinical improvement is discussed. a literature search in PubMed on the term "treatment of subclinical hypothyroidism" in combination with "quality of life", "weight", "cognition", and "cerebrovascular disease". current research supports that levothyroxine should be initiated in patients with a thyroid stimulating hormone (TSH) >10 mIU/L. Treatment for hypothyroidism is becoming more frequent. Symptoms related to vitality, weight, and quality of life in subclinical disease often persist with levothyroxine treatment, and other causes should be explored. Patients with cardiovascular-risk factors may benefit from treatment, especially younger patients. Caution is necessary when treating elderly subjects with levothyroxine. lifelong treatment with levothyroxine should normally only be considered in manifest hypothyroidism. However, in subclinical hypothyroidism with a TSH >10 mIU/L, therapy is indicated. In milder subclinical forms, a wait-and-see strategy is advocated to see if normalization occurs. Subgroups with cardiovascular risk and subclinical hypothyroidism may benefit from levothyroxine therapy.
Project description:No recent study has focused on clinical features of subclinical hypothyroidism (SCH), especially in older patients. TSH measurement has remarkably evolved these last 20 years and thus reconsideration is needed. In our prospective multicenter study (2012-2014) including 807 subjects aged <60 years (<60y) and 531 subjects ≥60 years (≥60y), we have monitored 11 hypothyroidism-related clinical signs (hCS) together with TSH, FT4, FT3 and anti-thyroperoxidase antibodies values. hCS expression has been compared in patients with SCH vs euthyroidism in each age group. The number of hCS above 60y of age were found to be more elevated in the euthyroid population (1.9 vs 1.6, p<0.01) than in the SCH population (2.3 vs 2.6, p=0.41) while increase in hCS is limited to SCH subjects in the <60y group (p<0.01). The percentage of subjects with at least 3 signs increased with SCH in the <60y group (42.6% vs 25.0%, p<0.01) but not ≥60y (34.4% vs 33.9%, p=0.96). In older individuals, only three hCS could be related to both SCH and a decreased T3/T4-ratio (0.26 vs 0.27, p<0.01), suggesting either a reduced activity of TSH, or an adaptive response with aging. While hCS are clearly associated with SCH in patients <60y, they are not so informative in older subjects. TSH measurements carried out on the basis of hCS need to be interpreted with caution in aged patients. A reassessment of the TSH reference range in older patients is clearly needed and should be associated to more appropriate monitoring of thyroid dysfunction.
Project description:ContextData regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease.ObjectiveTo assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism.Data sources and study selectionThe databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched.Data extractionIndividual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations.ResultsAmong 55,287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51,837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease.ConclusionsSubclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.
Project description:ObjectiveThyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes.MethodsIn total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45-4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45-60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke.ResultsMean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24-1.07) comparing subclinical hyperthyroidism and 0.90 (0.58-1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism).ConclusionsIn this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.
Project description:Background and aimPatients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression.MethodsWe included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated.ResultsAt baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (β = -5.77, p = 0.001), baseline renal function (β = -0.12, p < 0.001) and level of proteinuria (β = -2.36, p = 0.015) were independently associated with the rate of renal function decline.ConclusionsHalf of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline.