Color-Flow Doppler Sonography in Patients with Subclinical Thyroid Dysfunction

Objective To analyze the natural changes of maternal thyroid function among women with subclinical thyroid dysfunction and euthyroid women during pregnancy.Methods A total of 4 042 singleton pregnant women received routine antenatal care in the Obstetrics and Gynecology Hospital of Fudan University between April and November 2012 were enrolled.Thyroid-stimulatinghormones (TSH),freetriiodothyronine (FT3) and free thyroxine (FT4) of 7 136 samples from 4 042 singleton pregnant women were tested at 8-12+6,13-19+6,20-27+6,and 28-40 weeks of gestation and were used to establish the normal gestationalspecific reference values of thyroid function.Among 3 895 women having thyroid function tested at 8-19+6 weeks of gestation with negative thyroid antibodies,there were 93 cases of subclinical hyperthyroidism,91 cases of subclinical hypothyroidism (SCH),three cases of hyperthyroidism and 3 708 cases euthyroid.There were 1 118 women [1 607 euthyroid cases,17 cases of subclinical hypothyroidism (SCH) and 34 cases of subclinical hyperthyroidism] had thyroid function retested at 20-27+6 and 28-40 weeks of gestation,and without medicinal intervention.Analysis of variance and LSD test were used to analyze the changes of maternal thyroid function.Results (1) The reference ranges of TSH at 8-12+6,13-19+6,20 27+6 and 28-40 weeks of gestation [median (Pz5-P97.5)] were 1.32 (0.03-4.17),1.83 (0.19-4.94),2.27 (0.70-5.42) and 2.34 (0.63-5.52) mU/L respectively.(2) Without medicinal intervention,thyroid function became normal in 80％ (45/56) SCH women at 20-27+6 weeks,but 20％ (9/45) of them developed SCH again at 28-40 weeks.The thyroid function became normal in 75％ (70/93) women with subclinical hyperthyroidism at 20-27+6 weeks,but in 15％ (14/93) of them,thyroid function remained abnormal at 28-40 weeks.9.40％ (30/319) and 6.25％ (21/336) euthyroid women with TSH ≥ 3 mU/L at 8-19+6 weeks of gestation developed SCH at 20-27+6 weeks and 28-40 weeks,while 0.42％ (5/1 202) and 0.86％ (10/1 163) euthyroid women with TSH ＜3 mU/L had SCH.1.66％ (20/1 202) and 1.98％ (23/1 163) euthyroid women with TSH＜3 mU/L at 8-19+6 weeks of gestation developed subclinical hyperthyroidism at 20-27+6 weeks and 28-40 weeks of gestation.(3) In comparison between 8-19+6 weeks and 20-27+6 weeks of gestation,TSH levels increased by (0.47±0.03) mU/L in euthyroid women,and more significantly in subclinical hyperthyroidism women [(0.82±0.06) mU/L],but decreased by (1.67±0.25) mU/L in SCH women (LSD test,all P＜0.05).The FT3 levels decreased by (0.47±0.02) pmol/L in euthyroid women,and more significantly in subclinical hyperthyroidism and SCH groups [(1.02± 0.18) and (0.72±0.08) pmol/L,LSD test,all P＜0.05].FT4 decreased by (2.31 ±0.04) pmol/L in euthyroid women,and more significanly in subclinical hyperthyroidism women [(4.63± 0.62) pmol/L] (LSD test,P＜0.05),but the decrement in SCH group [(1.78±0.28) pmol/L] was similar to euthyroid women (LSD test,P＞0.05).There were no significant differences in changes of TSH,FT3 and FT4 at 20-27+6 weeks and 28-40 weeks among euthyroid women,SCH and subclinical hyperthyroidism groups (F=1.01,1.14 and 2.04,all P＞0.05).Conclusions Women with subclinical thyroid dysfunction with negative thyroid antibodies experience significantly different natural changes when compared with euthyroid women,especially before 28 weeks of gestation. Key words: Pregnancy complications; Hypothyroidism; Hyperthyroidism; Thyrotropin; Triiodothyronine; Thyroxine; Reference values

The Prevalence of Subclinical Thyroid Dysfunction and Its Association With Metabolic Syndrome in Taiwanese Elderly

Previous studies have suggested that subclinical thyroid dysfunction, as manifested by abnormalities in thyroid-stimulating hormone (TSH) levels, are associated with detrimental effects on the cardiovascular system. Subclinical hypothyroidism is characterized by abnormal lipid metabolism, cardiac dysfunction, diastolic hypertension conferring an elevated risk of atherosclerosis, and ischemic heart disease. Similarly, patients with subclinical hyperthyroidism have nearly 3 times the likelihood of atrial fibrillation over a 10-year follow-up interval, raising the question of whether patients with subclinical hyperthyroidism should be treated to prevent atrial fibrillation. A single measurement of low serum TSH in individuals aged 60 years or older has been reported to be associated with increased mortality from all causes and in particular from circulatory and cardiovascular disease in a 10-year follow-up study. Subclinical thyroid dysfunction is currently the subject of numerous studies and remains controversial, particularly as it relates to cardiovascular morbidity and mortality and clinical applications.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This project was supported by the MRes programme in the Institute of Life Course and Medical Sciences at The University of Liverpool. Thyroid hormones can act directly and indirectly on the cardiovascular system and studies have demonstrated associations between overt and subclinical thyroid dysfunction and adverse cardiovascular outcomes including heart failure, myocardial infarction, and coronary heart disease. The aim of this study was to assess the association between subclinical thyroid dysfunction and atrial fibrillation (AF). The protocol was registered on PROSPERO (CRD42020221565). MEDLINE and Scopus were searched from inception to 13th November 2020 for studies investigating subclinical thyroid dysfunction and incident AF. Risk of bias was assessed using the Risk of Bias Assessment Tool (RoBANS). The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Subgroup analysis was performed for post-operative and non-post-operative AF. 5413 records were identified. Nine cohort studies were suitable for inclusion in the systematic review, of which seven studies were included in the meta-analysis. The meta-analysis comprised 595,058 patients. Subclinical hyperthyroidism was associated with a 99% increase in the risk of incident AF (Risk ratio (RR): 1.99; 95% confidence intervals (CI); 1.43 to 2.77; p < 0.0001; I² = 67%). Subclinical hypothyroidism was also associated with a greater risk of AF (RR: 1.24; 95% CI; 1.05 to 1.47; p = 0.01; I² = 65%). Subgroup analysis demonstrated a 76% increase in the risk of post-operative AF in patients with subclinical hypothyroidism compared to euthyroid post-operative patients (RR: 1.76; 95% CI; 1.36 to 2.28; p < 0.0001; I² = 0%). Six studies were rated as low risk of bias and three as medium risk of bias according to the RoBANS tool. The quality of evidence for AF in subclinical hyper- and hypothyroid patients was low. Subclinical hyperthyroidism and subclinical hypothyroidism were associated with a higher risk of incident AF and post-operative AF, respectively. The quality of the current evidence is low and ideally a randomised controlled trial should be conducted to confirm these associations and assess impacts of treatments. Abstract Figure.

Edible mushrooms as a potent therapeutics of subclinical thyroid dysfunction among adults, especially in obese individuals: a prospective cohort study

Introduction: Thyroid disorders have been associated with depression over many years, but the mechanisms involved in this association are difficult to define and previous published data are still conflicting. The majority of studies were performed in Europe and the United States, with a recent increase in Asia, and it is unknown if their results would replicate in the Brazilian population. Therefore, ELSA-Brasil presents the opportunity to study the association between thyroid dysfunction and depression in the Brazilian population and prospectively. Methods: TSH, free-thyroxine (FT4) and anti-TPO antibodies levels were evaluated at baseline. Depression diagnoses were performed using the Clinical Interview Schedule -Revised (CIS-R) at baseline and after the 4-year-followup. The following analysis were performed using Poisson regression models (95% confidence interval, CI95%): (1) association between thyroid dysfunction (overt and subclinical) and incident depression; (2) association between anti-TPO antibodies and incident depression; (3) association between anti-TPO antibodies together with only overt/subclinical hypothyroidism and incident depression; (4) TSH levels (3 quintile as reference) and incident depression among those with subclinical thyroid dysfunction and euthyroid individuals; (5) TSH levels (3 quintile as reference) and incident depression among euthyroid individuals; (6) TSH levels (1 quintile as reference) and incident depression among those with subclinical thyroid dysfunction and euthyroid individuals; (7) TSH levels (1 quintile as reference) and incident depression among euthyroid individuals; (8) TSH levels were stratified by sex when appropriate, and the multivariable model was adjusted for age, sex, race, education, body mass index (BMI), smoking, alcohol consumption, use of antidepressants/benzodiazepines and comorbidities. Results: This study showed an inverse association between overt hypothyroidism and incident depression (RR=0,54; 95% CI 0,35-0,84), but no association was found for subclinical hypothyroidism, overt and subclinical hyperthyroidism. Also, there was no association between presence of anti-TPO antibodies and incident depression (even when analyzing it together with overt and/or subclinical hypothyroidism only). Regarding TSH levels, among those with subclinical thyroid dysfunction and euthyroid individuals, low TSH levels were associated with an increased risk of depression, for all participants (RR=1,36; 95% CI 1,02-1,81) and for women (RR=1,64; 95% CI 1,15-2,33). Even within the normal range, for all (RR=1,46; 95% CI 1,08-1,99) and for women (RR=1,63; 95% CI 1,12-2,38). High TSH levels were associated with a lower risk of depression, also for all participants (RR=0,71; 95% CI 0,53-0,96) and for women (RR=0,67; 95% CI 0,47-0,95). The sensibility analysis with TSH Conclusion: Overt hypothyroidism was associated with a lower risk of depression after 4 years of follow-up. The higher risk seems to be associated with low TSH levels among those with subclinical thyroid dysfunction and euthyorid individuals, even within the normal range. Specially among women. High TSH levels were associated with lower risk of depression, also for women. No association between TSH levels and incident depression was found among men.

Prevalence of subclinical thyroid disease increases with age, but optimal detection and surveillance strategies remain unclear particularly for older men. We aimed to assess thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations and their longitudinal changes, to determine the prevalence and incidence of subclinical thyroid dysfunction in older men. Longitudinal study of 994 community-dwelling men aged ≥70 years without known or current thyroid disease, with TSH and FT4 concentrations assessed at baseline and follow-up (after 8.7 ± 0.9 years). Factors associated with incident subclinical thyroid dysfunction were examined by logistic regression and receiver operating characteristic analyses. At baseline, 85 men (8.6%) had subclinical hypothyroidism and 10 (1.0%) subclinical hyperthyroidism. Among 899 men euthyroid at baseline (mean age 75.0 ± 3.0 years), 713 (79.3%) remained euthyroid, 180 (20.0%) developed subclinical/overt hypothyroidism, and 6 (0.7%) subclinical/overt hyperthyroidism. Change in TSH correlated with baseline TSH (r = .16, p < .05). Change in FT4 correlated inversely with baseline FT4 (r = -0.35, p < .05). Only higher age and baseline TSH predicted progression from euthyroid to subclinical/overt hypothyroidism (fully-adjusted odds ratio [OR] per year=1.09, 95% confidence interval [CI] = 1.02-1.17, p = .006; per 2.7-fold increase in TSH OR = 65.4, CI = 31.9-134, p < .001). Baseline TSH concentration ≥2.34 mIU/L had 76% sensitivity and 77% specificity for predicting development of subclinical/overt hypothyroidism. In older men TSH concentration increased over time, while FT4 concentration showed little change. Subclinical or overt hypothyroidism evolved in one fifth of initially euthyroid men, age and higher baseline TSH predicted this outcome. Increased surveillance for thyroid dysfunction may be justified in older men, especially those with high-normal TSH.

We aimed to investigate the association of subclinical thyroid disease and thyroid hormone levels with sarcopenia and its defining components in community-dwelling middle-aged and older adults without overt thyroid dysfunction. Cross-sectional study. Active and retired employees from public institutions located in six Brazilian cities. A total of 6974 participants from the ELSA-Brasil study's second wave, aged 50 years and older, without overt thyroid dysfunction and with complete data for exposure, outcome, and covariates. Serum levels of thyrotropin (TSH), free thyroxine, and free triiodothyronine (FT3) were measured and divided in quintiles for the analyses. Participants were classified with euthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism. Muscle mass was assessed by bioelectrical impedance analysis and muscle strength by handgrip strength. Sarcopenia was defined according to the Foundation for the National Institutes of Health criteria. Possible confounders included sociodemographic characteristics, clinical conditions, and lifestyle. Analyses were performed separately for middle-aged and older adults (≥65 y). The frequencies of sarcopenia, low muscle mass, low muscle strength, subclinical hypothyroidism, and subclinical hyperthyroidism were 1.5%, 20.8%, 3.8%, 9.1%, and .9%, respectively. Subclinical thyroid dysfunction was not associated with sarcopenia and its defining components. Among older adults, TSH had a U-shaped association with sarcopenia and low muscle strength. The odds ratios (ORs) (95% confidence intervals [CIs]) for the associations of the first, second, fourth, and fifth quintile with sarcopenia, respectively, were 5.18 (1.47-18.28), 6.28 (1.82-21.73), 4.12 (1.15-14.76), and 4.81 (1.35-17.10), and with low muscle strength was (OR (95% CI) for the first, second, and fifth quintiles, respectively: 1.43 (1.16-5.07), 2.07 (1.24-4.70), and 2.18 (1.03-4.60). Additionally, FT3 had a negative association with muscle mass in both age strata. Subtle thyroid hormone alterations are associated with sarcopenia or its defining components in middle-aged and older adults without overt thyroid dysfunction. J Am Geriatr Soc 68:1545-1553, 2020.

Acute myocardial infarction and subclinical hyperthyroidism without significant coronary stenoses

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. The objective of the study was to determine the prevalence of subclinical thyroid dysfunction and unidentified overt thyroid dysfunction in an elderly population. 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 included current therapy for thyroid disease, thyroid surgery, or treatment within 12 months. 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). Standardized prevalence rates were analyzed. Logistic regression modeling was used to determine factors associated with the presence of subclinical thyroid dysfunction. 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. 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.

Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels.

To review information on the benefits of screening with a sensitive thyroid-stimulating hormone (TSH) test for thyroid dysfunction in asymptomatic patients seeking primary care for other reasons. This paper focuses on whether screening should be aimed at detection of subclinical thyroid dysfunction and whether persons with mildly abnormal TSH levels can benefit. A MEDLINE search for studies of screening for thyroid dysfunction and of treatment for complications of subclinical thyroid dysfunction. Studies of screening with thyroid function tests in the general adult population or in patients seen in the general office setting were selected (n=33). All controlled studies of treatment in patients with subclinical hypothyroidism or subclinical hyperthyroidism were also included (n=23). The prevalence of overt and subclinical thyroid dysfunction, the evidence for the efficacy of treatment, and the incidence of complications in defined age and sex groups were extracted from each study. Screening can detect symptomatic but unsuspected overt thyroid dysfunction. The yield is highest for women older than 50 years of age: In this group, 1 in 71 women screened could benefit from relief of symptoms. Evidence of the efficacy of treatment for subclinical thyroid dysfunction is inconclusive. Even though treatment for subclinical thyroid dysfunction is controversial, office-based screening to detect overt thyroid dysfunction may be indicated in women older than 50 years of age. Large randomized trials are needed to determine the likelihood that treatment will improve quality of life in otherwise healthy patients who have mildly elevated TSH levels.

A highly sensitive immunoassay for thyroid-stimulating hormone (TSH) was developed in the 1980's for the diagnosis of patients with subclinical thyroid dysfunctions. The frequency of subclinical hypothyroidism is 4.3–11.8% and that of subclinical hyperthyroidism is 0.7–1.5%.1 An association between subclinical hypothyroidism and cardiovascular risks and the development of atherosclerosis has been reported.2 Subclinical hyperthyroidism reportedly increases heart rate, the frequency of arrhythmia (including atrial fibrillation), left ventricular mass and the risk of cardiovascular mortality; it also impairs ventricular relaxation.3 However, the relationship between subclinical thyroid dysfunction and hypertension has remained controversial.

IntroductionProspective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree...

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.