Thyroid function and prevalent and incident metabolic syndrome in older adults: the Health, Ageing and Body Composition Study

Objective Both subclinical hypothyroidism and the metabolic syndrome have been associated with increased risk of coronary heart disease events. It is unknown whether the prevalence and incidence of metabolic syndrome is higher as TSH levels increase, or in individuals with subclinical hypothyroidism. We sought to determine the association between thyroid function and the prevalence and incidence of the metabolic syndrome in a cohort of older adults. Design Data were analysed from the Health, Ageing and Body Composition Study, a prospective cohort of 3075 community‐dwelling US adults. Participants Two thousand one hundred and nineteen participants with measured TSH and data on metabolic syndrome components were included in the analysis. Measurements TSH was measured by immunoassay. Metabolic syndrome was defined per revised ATP III criteria. Results At baseline, 684 participants met criteria for metabolic syndrome. At 6‐year follow‐up, incident metabolic syndrome developed in 239 individuals. In fully adjusted models, each unit increase in TSH was associated with a 3% increase in the odds of prevalent metabolic syndrome (OR, 1·03; 95% CI, 1·01–1·06; P = 0·02), and the association was stronger for TSH within the normal range (OR, 1·16; 95% CI, 1·03–1·30; P = 0·02). Subclinical hypothyroidism with a TSH > 10 mIU/l was significantly associated with increased odds of prevalent metabolic syndrome (OR, 2·3; 95% CI, 1·0–5·0; P = 0·04); the odds of incident MetS was similar (OR 2·2), but the confidence interval was wide (0·6–7·5). Conclusions Higher TSH levels and subclinical hypothyroidism with a TSH > 10 mIU/l are associated with increased odds of prevalent but not incident metabolic syndrome.     

Prevalence of subclinical thyroid dysfunction and its relation to socioeconomic deprivation in the elderly: a community-based cross-sectional survey

CONTEXT: Population-based screening has been advocated for subclinical thyroid dysfunction in the elderly because the disorder is perceived to be common, and health benefits may be accrued by detection and treatment. OBJECTIVE: The objective of the study was to determine the prevalence of subclinical thyroid dysfunction and unidentified overt thyroid dysfunction in an elderly population. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional survey of a community sample of participants aged 65 yr and older registered with 20 family practices in the United Kingdom. EXCLUSIONS: Exclusions included current therapy for thyroid disease, thyroid surgery, or treatment within 12 months. OUTCOME MEASURE: Tests of thyroid function (TSH concentration and free T4 concentration in all, with measurement of free T3 in those with low TSH) were conducted. EXPLANATORY VARIABLES: These included all current medical diagnoses and drug therapies, age, gender, and socioeconomic deprivation (Index of Multiple Deprivation, 2004). ANALYSIS: Standardized prevalence rates were analyzed. Logistic regression modeling was used to determine factors associated with the presence of subclinical thyroid dysfunction. RESULTS: A total of 5960 attended for screening. Using biochemical definitions, 94.2% [95% confidence interval (CI) 93.8-94.6%] were euthyroid. Unidentified overt hyper- and hypothyroidism were uncommon (0.3, 0.4%, respectively). Subclinical hyperthyroidism and hypothyroidism were identified with similar frequency (2.1%, 95% CI 1.8-2.3%; 2.9%, 95% CI 2.6-3.1%, respectively). Subclinical thyroid dysfunction was more common in females (P < 0.001) and with increasing age (P < 0.001). After allowing for comorbidities, concurrent drug therapies, age, and gender, an association between subclinical hyperthyroidism and a composite measure of socioeconomic deprivation remained. CONCLUSIONS: Undiagnosed overt thyroid dysfunction is uncommon. The prevalence of subclinical thyroid dysfunction is 5%. We have, for the first time, identified an independent association between the prevalence of subclinical thyroid dysfunction and deprivation that cannot be explained solely by the greater burden of chronic disease and/or consequent drug therapies in the deprived population.     

Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure

We aimed to analyze the natural course of subclinical hypothyroidism, quantify the incidence rate of overt hypothyroidism, and evaluate the risk factors for the development of definitive thyroid failure in elderly patients. One hundred seven patients (93 women and 14 men) over age 55 yr with subclinical hypothyroidism and no previous history of thyroid disease were prospectively studied. Subjects were followed up for 6-72 months (mean, 31.7 months) with repeated determinations of TSH and free T(4). Twenty-eight patients (26.8%) developed overt hypothyroidism, and 40 (37.4%) showed normalization of their TSH values. The incidence rate of overt hypothyroidism was 9.91 cases per 100 patient-years in the whole population, and 1.76, 19.67, and 73.47 cases per 100 patient-years in subjects with initial TSH values between 5.0-9.9, 10.0-14.9, and 15.0-19.9 mU/liter, respectively. Kaplan-Meier analysis showed that the development of definitive thyroid hypofunction was significantly related to the presence of symptoms of hypothyroidism, goiter, positive thyroid antibodies (P < 0.05), and mainly low normal free T(4) (P < 0.01) and high TSH (P < 0.0001) concentrations at baseline. A stepwise multivariate Cox regression analysis showed that the only significant factor for progression to overt hypothyroidism was serum TSH concentration (P < 0.0001). In conclusion, TSH concentration is the most powerful predictor for the outcome of spontaneous subclinical hypothyroidism in patients over age 55 yr. Subjects with mildly elevated TSH have a low incidence rate of overt hypothyroidism. We recommend follow-up with clinical and biochemical monitoring in these patients.     

A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure

OBJECTIVE: Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism. DESIGN: A population study including 4649 randomly selected subjects. MEASUREMENTS: Blood tests were used to analyse for thyroid peroxidase autoantibodies (TPO-Ab), thyroglobulin autoantibodies (Tg-Ab), TSH, fT3 and fT4. RESULTS: Thyroid volume was categorized as small (< 6.6 ml) in 4.7%, normal (6.6-14.9 ml) in 60.4% and large (> 14.9 ml) in 34.9% of participants. Thyroid nodules were found in 29.7%. Serum TSH was low (< 0.4 mIU/l) in 4.7%, normal (0.4-3.6) in 91.0% and high (> 3.6) in 4.3%. The prevalence rate of subclinical goitrous Hashimoto's disease was 0.62% and of subclinical autoimmune atrophic thyroiditis 0.24%. There was a strong association between large volume and autoantibodies, but only in subjects with elevated TSH (P < 0.001). An association between thyroid nodules and TPO-Ab in univariate analyses (P < 0.001) was due to confounding by sex and age (multivariate model, P = 0.23). CONCLUSION: We identified a subgroup of the population with subclinical goitrous Hashimoto's disease and a smaller subgroup with subclinical autoimmune atrophic thyroiditis. This relationship between small and large thyroid volume in subclinical disease is opposite to that in overt disease, which may suggest that the period between development of a small volume with circulating autoantibodies and overt hypothyroidism is relatively short.     

The prevalence of undiagnosed thyroid disorders in a previously iodine-deficient area.

OBJECTIVE: The aim of the present study was to analyze the current status of morphologic and functional thyroid abnormalities in a previously iodine-deficient area. METHODS: The population based Study of Health in Pomerania (SHIP) comprised 4310 participants, aged 20-79 years. Thyroid function (thyrotropin [TSH] free triiodothyronine [FT(3)], and free thyroxine [FT(4)]) and serum autoantibodies to thyroperoxidase (TPOAb) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. Data from 3941 participants with no known thyroid disorders were analyzed. RESULTS: The median iodine urine excretion was 12.4 microg/dL. The rate of decreased serum TSH levels (<0.3 mIU/L) was 11.3%; 2.2% of participants had suppressed serum TSH levels (<0.1 mIU/L). The prevalence of subclinical hyperthyroidism was 1.8%, the prevalence of overt hyperthyroidism 0.4%. Elevated TSH levels were found in 1.2% of individuals. Subclinical hypothyroidism was observed in 0.5%, overt hypothyroidism in 0.7% of the sample. Elevated TPOAb were detected in 7% of subjects, 4.1% of participants had TPOAb greater than 200 IU/mL. The prevalence of goiter was 35.9%. An inhomogeneous echo pattern was detected in 35.2% and nodules in 20.2% of participants. Diffuse autoimmune thyroiditis was diagnosed in 47 subjects (1.2%). CONCLUSION: There are a number of thyroid disorders in this previously iodine-deficient region. Further studies are required to investigate the change of thyroid disorders during iodine supplementation programs.     

Thyroid Function Abnormalities and Cognitive Impairment in Elderly People: Results of the Invecchiare in Chianti Study

OBJECTIVES: To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition.
DESIGN: Cross-sectional.
SETTING: Community-based.
PARTICIPANTS: One thousand one hundred seventy-one men and women aged 23 to 102.
MEASUREMENTS: Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 vs ≥65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders.
RESULTS: Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P <.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P <.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61±6.88 vs 24.72±4.52, P <.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P =.003).
CONCLUSION: Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment.     

Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death

BACKGROUND: Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited. METHODS: We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and > or = 10.0 mIU/L). RESULTS: Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P = .006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of > or = 10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P = .03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure.     

Subclinical Thyroid Dysfunction and the Risk of Heart Failure Events: An Individual Participant Data Analysis From 6 Prospective Cohorts

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.     

Prevalence and progression of subclinical hypothyroidism in women with type 2 diabetes: the Fremantle Diabetes Study

OBJECTIVE: To assess the prevalence and progression of subclinical hypothyroidism in women with type 2 diabetes. DESIGN AND PATIENTS: Cross-sectional and longitudinal observational assessment of thyroid function in 420 adult females with type 2 diabetes randomly selected from participants in the community-based Fremantle Diabetes Study. Measurements Serum TSH, antibodies to thyroperoxidase (anti-TPO) and serum free T4 were measured at baseline and after 5 years. Baseline glycated haemoglobin (HbA(1c)), serum glucose, serum total and high density lipoprotein (HDL) cholesterol, serum triglycerides and antibodies to glutamic acid decarboxylase (anti-GAD) were also used in analyses. RESULTS: After exclusion of patients with known thyroid disease or taking amiodarone or lithium at baseline, the prevalence of subclinical hypothyroidism (a raised serum TSH and normal serum free T4) was 8.6%. Subclinical hypothyroidism was associated with anti-TPO status and age, but there were no independent associations with serum cholesterol, history of coronary heart disease, HbA(1c) or hypoglycaemic therapy. In the subgroup of patients restudied after 5 years, none of those who had subclinical hypothyroidism at baseline had overt hypothyroidism regardless of anti-TPO status. CONCLUSIONS: In women with type 2 diabetes without known thyroid disease, subclinical hypothyroidism is a common but incidental finding. The routine screening of thyroid function in type 2 diabetes is questionable.     

Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin,thyroid reserve,and thyroid antibodies

Subclinical hypothyroidism is a frequent syndrome affecting about 10 million people in the United States. The management of such patients is open to debate. In a long-term prospective study we analyzed the spontaneous course and the value of predictive factors in the development of overt thyroid failure. We studied 82 female patients with subclinical hypothyroidism prospectively over a mean observation period of 9.2 yr. TSH, thyroid hormones, thyroid reserve after TRH administration, thyroid antibodies, and clinical parameters were assessed at yearly intervals. The cumulative incidence of overt hypothyroidism was calculated using life-table analysis and Kaplan-Meier curves. According to the initial serum TSH concentrations (TSH, 4-6/>6-12/>12 mU/liter), Kaplan-Meier estimates of the incidence of overt hypothyroidism were 0%, 42.8%, and 76.9%, respectively, after 10 yr (P < 0.0001). When only patients with TSH levels greater than 6 mU/liter were analyzed, the cumulative incidence was 55.3%. The incidence of overt hypothyroidism increased in patients with impaired thyroid reserve (52.6% vs. 38.1%; P = 0.05) and positive microsomal antibodies (58.5% vs. 23.2%; P = 0.03). This prospective long-term study demonstrates that only a part of the cohort of patients with subclinical hypothyroidism develops overt hypothyroidism over time and that a major group remains in the subclinical state after 10 yr. The measurement of TSH, microsomal (thyroperoxidase) antibodies, and thyroid reserve allows initial risk stratification for the development of overt thyroid failure (risk ratio ranging from 1.0-15.6). Our study helps to recognize the spontaneous course of subclinical hypothyroidism and in the identification of patients most likely to progress to overt hypothyroidism.     

Tobacco smoking and thyroid function: a population-based study

BACKGROUND: The association between tobacco smoking and thyroid function is incompletely understood. METHODS: In a cross-sectional, population-based study conducted between August 15, 1995, and June 18, 1997, of 20 479 women and 10 355 men without previously known thyroid disease, we calculated the geometric mean serum concentration of thyrotropin and the prevalence of hypothyroidism and hyperthyroidism among current, former, and never smokers. RESULTS: Among women, the mean thyrotropin level was lower in current (1.33 mIU/L; 95% confidence interval [CI], 1.29-1.36 mIU/L) and former smokers (1.61 mIU/L; 95% CI, 1.56-1.65 mIU/L) compared with never smokers (1.66 mIU/L; 95% CI, 1.63-1.70 mIU/L). Similarly, among men, the mean thyrotropin level was lower in current (1.40 mIU/L; 95% CI, 1.36-1.44 mIU/L) and former smokers (1.61 mIU/L; 95% CI, 1.57-1.66 mIU/L) compared with never smokers (1.70 mIU/L; 95% CI, 1.66-1.75 mIU/L). In former smokers, thyrotropin levels increased gradually with time since smoking cessation (P for trend < .001). Among current smokers, moderate daily smoking was associated with higher thyrotropin levels than heavier smoking. In women, the prevalence of overt hypothyroidism was lower in current smokers compared with never smokers (odds ratio, 0.60; 95% CI, 0.38-0.95), whereas the prevalence of overt hyperthyroidism was higher among current smokers (odds ratio, 2.37; 95% CI, 1.34-4.20). The associations related to subclinical thyroid dysfunction were similar to those for overt thyroid disease. CONCLUSIONS: These findings indicate that smoking is negatively associated with hypothyroidism but positively associated with hyperthyroidism. The associations with smoking cessation suggest that smoking may have reversible effects on thyroid function. Notably, we report for the first time, to our knowledge, a lower prevalence of overt hypothyroidism among current smokers.     

Prenatal dexamethasone use for the prevention of virilization in pregnancies at risk for classical congenital adrenal hyperplasia because of 21‐hydroxylase (CYP21A2) deficiency: a systematic review and meta‐analyses

A mildly increased serum thyrotrophin (TSH) is usually because of mild thyroid failure, and the most common aetiology in iodine‐replete communities is chronic autoimmune thyroiditis. It is more common in women, and the prevalence increases with age in both men and women and is associated with the presence of antithyroid antibodies. The majority will have serum TSH levels between 5–10 mIU/l, normal free thyroxine (T4) levels and relatively few symptoms. In 2004, US evidence‐based consensus guidelines concluded that there were no adverse outcomes of a mildly increased serum TSH other than a risk of progression to overt hypothyroidism and few data to justify levothyroxine therapy. There is still debate as to what constitutes an increased serum TSH, particularly in older subjects. Although some subjects will progress to overt hypothyroidism, recent data suggest a significant proportion revert to a serum TSH within the reference range without treatment. Two recent meta‐analyses have suggested that the possible cardiovascular risks may be more significant in younger adults. Other data suggest that mild thyroid failure may be the only reversible cause of left ventricular diastolic dysfunction. No appropriately powered prospective, randomized, controlled, double‐blinded interventional trial of levothyroxine therapy for a mildly increased serum TSH exists. However, treatment in subjects who are symptomatic, pregnant or preconception, aged less than 65 years and older subjects with evidence of heart failure appear justified.     

Influence of iodine on the reference interval of TSH and the optimal interval of TSH: results of a follow-up study in areas with different iodine intakes

Objective The aim of the present study was to evaluate whether the status of iodine nutrition influences the TSH concentration in a selected Chinese reference population according to the criteria proposed by National Academy of Clinical Biochemistry (NACB) and regular thyroid ultrasonography, to establish a new reference interval of TSH based on the wide variation of iodine nutrition in populations, and to identify an optimal interval of TSH by following up the cohort with normal TSH concentrations at baseline. Design The study was conducted in Panshan, Zhangwu and Huanghua, the regions with mildly deficient, more than adequate and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 2237 met the criteria for a reference population. Of 3048 subjects with normal serum TSH at baseline, 2727 (80·0%) participated in the 5‐year follow‐up study. TSH and thyroid autoantibodies in serum and iodine in urine were measured, and B‐mode ultrasonography of the thyroid was performed. Results In the reference population, there was a urinary iodine‐related increment of serum TSH levels (r = 0·21, P = 0·000), and the mean levels of TSH in Panshan, Zhangwu and Huanghua were 1·15, 1·28 and 1·93 mIU/l, respectively (P = 0·000), corresponding to the rising regional iodine intake. Based on the overall data, we obtained a reference interval of 0·3–4·8 mIU/l. TSH concentrations obtained in the follow‐up study correlated well with those at baseline (r = 0·58, P = 0·000). A baseline serum TSH > 1·9 mIU/l was associated with an increased incidence of development of supranormal TSH and a baseline serum TSH < 1·0 mIU/l was associated with an increased incidence of subnormal TSH development. Conclusions Iodine nutrition is an important factor associated with TSH concentration even in the rigorously selected reference population. Baseline TSH of 1·0–1·9 mIU/l is an optimal interval with the lowest incidence of abnormal TSH in 5 years.     

Are serum TSH levels associated with oxidized low‐density lipoprotein? Results from the Study of Health in Pomerania

Objective Oxidized LDL (oxLDL) is involved in the pathogenesis of atherosclerosis. Thus, it is important to investigate putative risk factors for increased oxLDL. Evidence suggests that, compared to euthyroid individuals, LDL‐cholesterol (LDL‐C) levels are lower in individuals with overt hyperthyroidism. Whereas oxidization of LDL‐C into oxLDL is increased in overt hyper‐ and hypothyroidism, it has not been investigated whether subclinical thyroid dysfunction impacts on oxLDL levels in general. We have analysed the association between serum thyrotrophin (TSH) levels and oxLDL in a population‐based study. Design, Patients and Measurements Of the 4308 individuals enrolled in the Study of Health in Pomerania, data from 3519 individuals were analysed (680 missing the oxLDL variable). oxLDL was measured by the oxLDL competitive ELISA on a BEP 2000. Multivariable linear regression models were performed to assess the association between serum TSH and oxLDL levels. Results TSH was positively associated with oxLDL in a curvilinear fashion with increasing serum TSH levels. Subgroup analyses revealed a significant association only in the group of individuals >60 years. Additionally, serum TSH levels were not associated with the ratio of oxLDL to LDL (β = ?0·04; 95% CI = ?0·08, 0·01; P = 0·084). Conclusions We demonstrate an association between serum TSH and oxLDL levels especially in the range of subclinical thyroid disease. Our study suggests that serum TSH levels affect LDL‐C production or clearance rather than the LDL‐C oxidation processes.     

Community-based study of the association of subclinical thyroid dysfunction with blood pressure

The relationship between subclinical thyroid dysfunction and blood pressure has been controversial and received unsufficient attention. Thus, we performed a cross-sectional study conducted among 6,992 inhabitants from six districts of Jiangsu Province to investigate the association of subclinical thyroid dysfunction with blood pressure in China. The data from 6,583 subjects (4,115 women and 2,468 men) were included and divided into three groups: euthyroidism (n = 5669, 86.11%), subclinical hyperthyroidism (n = 108, 1.65%), and subclinical hypothyroidism (n = 806, 12.24%). In the groups with subclinical hypothyroidism and hyperthyroidism, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were not significantly different from those in the groups with euthyroidism after being adjusted for age, sex, BMI, and smoking status (P > 0.05). More extensively, the SBP and DBP in the group of subclinical hypothyroidism with lower level of TSH (TSH 4.51–10.00 mIU/l, SCH₁) were significantly higher than those of participants with euthyroidism (P < 0.05). Multivariable logistic analysis revealed that subclinical hypothyroidism with lower TSH (TSH 4.51–10.00 mIU/l) was an independent risk factor for increased SBP (OR = 1.28, 95% CI 1.03–1.59, P = 0.028). Similar results could not be found between groups of euthyroid and subclinical hypothyroid with higher level of TSH (TSH > 10 mIU/l, SCH₂). Further subdivision of the euthyroid group on the basis of a TSH cut-off of 2.5 mIU/l, revealed still no significant difference in blood pressure after adjustment regardless of whether the TSH levels were in the lower reference (TSH 0.40–2.50 mIU/l, n = 4093) or in the upper reference ranges (TSH 2.51–4.50 mIU/l, n = 1576) (P > 0.05). We concluded that subclinical thyroid dysfunction was not associated with blood pressure. Neither subclinical hyperthyroidism nor subclinical hypothyroidism independently predicted increased blood pressure.     

Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults: A Review of the Literature

The estimated prevalence of subclinical hypothyroidism (SCH) in the general population is 3% to 8%. As the average age of the population in the United States and other countries continues to increase, the overall prevalence of SCH may also be expected to increase. Although age‐related changes in thyroid function are well described, normal thyroid‐stimulating hormone (TSH) reference limits, derived for age‐specific populations, are not routinely used to identify thyroid dysfunction in elderly adults. Therefore, currently accepted values for the upper limit of normal of TSH may be inappropriate for diagnosing SCH in individuals aged 65 and older, resulting in potential overestimation of the prevalence of SCH in this population. This review discusses the current evidence of the effects of SCH on cardiovascular health and neuropsychiatric function in older adults. Although the results of some studies are conflicting, the overall evidence suggests that the consequences of SCH may be different for elderly adults than for younger populations. Treatment of SCH in older individuals requires special consideration with regard to thyroid hormone replacement therapy and expected clinical outcomes. Although careful identification of individuals with persistent SCH who could benefit from levothyroxine treatment is necessary, current evidence suggests that individuals with TSH levels greater than 10 mIU/L who test positive for antithyroid antibodies or are symptomatic may benefit from levothyroxine treatment to reduce the risk of progression to overt hypothyroidism, decrease the risk of adverse cardiovascular events, and improve their quality of life. After treatment is initiated, careful monitoring is essential.     

Does Treating Subclinical Hypothyroidism Improve Markers of Cardiovascular Risk?

Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone values. The overall prevalence of subclinical hypothyroidism is 4-10% in the general population and up to 20% in women aged >60 years. The potential benefits and risks of therapy for subclinical hypothyroidism have been debated for 2 decades, and a consensus is still lacking. Besides avoiding the progression to overt hypothyroidism, the decision to treat patients with subclinical hypothyroidism relies mainly on the risk of metabolic and cardiovascular alterations. Subclinical hypothyroidism causes changes in cardiovascular function similar to, but less marked than, those occurring in patients with overt hypothyroidism. Diastolic dysfunction both at rest and upon effort is the most consistent cardiac abnormality in patients with subclinical hypothyroidism, and also in those with slightly elevated TSH levels (>6 mIU/L). Moreover, mild thyroid failure may increase diastolic blood pressure as a result of increased systemic vascular resistance. Restoration of euthyroidism by levothyroxine replacement is generally able to improve all these abnormalities. Early clinical and autopsy studies had suggested an association between subclinical hypothyroidism and coronary heart disease, which has been subsequently confirmed by some, but not all, large cross-sectional and prospective studies. Altered coagulation parameters, elevated lipoprotein (a) levels, and low-grade chronic inflammation are regarded to coalesce with the hypercholesterolemia of untreated patients with subclinical hypothyroidism to enhance the ischemic cardiovascular risk. Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. On the other hand, levothyroxine replacement therapy can always be discontinued if there is no apparent benefit. Levothyroxine replacement therapy is usually safe providing that excessive administration is avoided by monitoring serum TSH levels. However, the possibility that restoring euthyroidism may be harmful in the oldest of the elderly population of hypothyroid patients has been recently raised, and should be taken into account in making the decision to treat patients with subclinical hypothyroidism who are aged >85 years.     

The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding?

OBJECTIVE: In order to determine whether screening of thyroid function is justified in patients with hypercholesterolaemia, we determined the prevalence of subclinical hypothyroidism at different levels of total plasma cholesterol in middle-aged men and women. DESIGN AND METHODS: 1200 participants were selected from a population based cross sectional study on risk factors for cardiovascular diseases. The participants were divided into three groups: total plasma cholesterol < 5 mmol/l, total plasma cholesterol 5-8 mmol/l, total plasma cholesterol > 8 mmol/l. Each group was comparable in size and sex distribution. Subclinical hypothyroidism was defined as plasma TSH levels higher than 4 mU/l, in the presence of normal free thyroxine (FT4(4)) concentration. RESULTS: Plasma samples of a total of 1191 participants were analyzed. The overall prevalence of subclinical hypothyroidism was 1.9% in men and 7.6% in women of middle age. In women the prevalence of subclinical hypothyroidism increased from 4.0 percent in the lowest, to 10.3 percent in the highest cholesterol stratum (P = 0.02). In men, the mean prevalence was 1.8 percent and roughly similar in the various strata. After age correction, an increase of 1 mU/l TSH in women was associated with an increase of 0.09 mmol/l total plasma cholesterol (95% confidence interval (CI) 0.02-0.16 mmol/l). A similar trend was found in men (0.16 mmol/l, 95% CI -0.02-0.34 mmol/l). CONCLUSIONS: In the population, the prevalence of subclinical hypothyroidism is up to 10 percent in middle aged women with high levels of total plasma cholesterol and may justify case-finding. In these women approximately 0.5 mmol/l of total plasma cholesterol can be attributed to the subclinical thyroid dysfunction. In men a similar correlation between thyroid dysfunction and total plasma cholesterol is seen, but the prevalence of thyroid dysfunction is considerably lower.