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Subclinical hypothyroidism and cognitive function in people over 60 years: a systematic review and meta-analysis.

ABSTRACT: Subclinical hypothyroidism (SCH), defined as elevated thyroid stimulating hormone (TSH) and normal thyroid hormone levels, and cognitive impairment are both common in older people. While the relation between overt hypothyroidism and cognitive impairment is well established, data on the association between SCH and cognitive impairment are conflicting. This systematic review and meta-analysis was performed to assess available evidence on the association of SCH with cognition in community dwelling, relatively healthy older adults. PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, PsycINFO, and Academic Search Premier (January 1966 to April 1, 2015) were searched without language restrictions, as were references of key articles, for studies on the association between SCH and cognition in older adults (>60 years). These studies were reviewed by two independent reviewers according to predefined criteria for eligibility and methodological quality, and data were extracted using standardized forms. Of the 844 reports initially identified, 270 remained after exclusion of duplicates. Of the 270, 15 studies comprising 19,944 subjects, of whom 1,199 had subclinical hypothyroidism were included. Data from the 15 studies was pooled, and meta-analyzed cross-sectionally for global cognition [assessed by Mini-Mental State Examination (MMSE)], executive function, and memory, using random effects models. Pooled effect size (ES) for MMSE was -0.01 (95% CI -0.09, 0.08), with heterogeneity (I (2)) of 55.1%. Pooled ES was < 0.001 (95% CI -0.10, 0.09) for executive function (I (2) = 13.5%), and 0.01 (95% CI -0.12, 0.14) for memory (I (2) = 46.9%). In addition, prospective analysis including four studies showed pooled ES of 0.033 (95% CI -0.001 - 0.067) for MMSE (I (2) < 0.001%), indicating that subclinical hypothyroidism was not significantly associated with accelerated cognitive decline. This systematic review and meta-analysis provides no evidence that supports an association between SCH and cognitive impairment in relatively healthy older adults.

SUBMITTER: Akintola AA

PROVIDER: S-EPMC4531303 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Subclinical hypothyroidism and cognitive function in people over 60 years: a systematic review and meta-analysis.

Akintola Abimbola A AA Jansen Steffy W SW van Bodegom David D van der Grond Jeroen J Westendorp Rudi G RG de Craen Anton J M AJ van Heemst Diana D

Frontiers in aging neuroscience 20150811

Subclinical hypothyroidism (SCH), defined as elevated thyroid stimulating hormone (TSH) and normal thyroid hormone levels, and cognitive impairment are both common in older people. While the relation between overt hypothyroidism and cognitive impairment is well established, data on the association between SCH and cognitive impairment are conflicting. This systematic review and meta-analysis was performed to assess available evidence on the association of SCH with cognition in community dwelling, ...[more]

PMID: 26321946

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Project description:BackgroundSubclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base.MethodsThe IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ?4.6 and???19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure.DiscussionThe combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date.Trial registrationNederlands (Dutch) Trial Register: NTR3851 (12-02-2013), EudraCT: 2012-004160-22 (17-02-2013), ABR-41259.058.13 (12-02-2013).

Project description:Abundant evidence suggests an association between subclinical hypothyroidism (SCH) and type 2 diabetes mellitus (T2DM), but small sample sizes and inconclusive data in the literature complicate this assertion.We measured the prevalence of SCH in T2DM population, and investigated whether T2DM increase the risk of SCH and whether SCH was associated with diabetic complications.We conducted a meta-analysis using PubMed, EMBASE, Web of Science, Wan Fang, CNKI and VIP databases for literature search. We obtained studies published between January 1, 1980 to December 1, 2014. The studies were selected to evaluate the prevalence of SCH in T2DM subjects, compare the prevalence of SCH in T2DM subjects with those non-diabetics, and investigate whether diabetic complications were more prevalent in SCH than those who were euthyroid. Fixed and random effects meta-analysis models were used, and the outcome was presented as a pooled prevalence with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI.Through literature search, 36 articles met the inclusion criteria and these articles contained a total of 61 studies. Funnel plots and Egger's tests showed no publication bias in our studies, except for the pooled prevalence of SCH in T2DM (P = 0.08) and OR for SCH in T2DM (P = 0.04). Trim and fill method was used to correct the results and five potential missing data were replaced respectively. The adjusted pooled prevalence of SCH in T2DM patients was 10.2%, meanwhile, T2DM was associated with a 1.93-fold increase in risk of SCH (95% CI: 1.66, 2.24). Furthermore, SCH might affect the development of diabetic complications with an overall OR of 1.74 (95% CI: 1.34, 2.28) for diabetic nephropathy, 1.42 (95% CI: 1.21, 1.67) for diabetic retinopathy, 1.85 (95% CI: 1.35, 2.54) for peripheral arterial disease, and 1.87 (95% CI: 1.06, 3.28) for diabetic peripheral neuropathy.T2DM patients are more likely to have SCH when compared with healthy population and SCH may be associated with increased diabetic complications. It is necessary to screen thyroid function in patients with T2DM, and appropriate individualized treatments in addition to thyroid function test should be given to T2DM patients with SCH as well.

Project description:ObjectiveStudies have shown a high incidence of subclinical hypothyroidism in pregnancy, but the adverse pregnancy outcomes caused by it are not clear. Therefore, we conducted a systematic review and meta-analysis to evaluate the relationship between subclinical hypothyroidism in pregnancy and hypertensive disorders of pregnancy(HDP) to guide clinical practice.MethodWe searched the MEDLINE (PubMed), Cochrane Central, EMBASE, Web of Science, and SCOPUS databases and screened all studies evaluating the relationship between subclinical hypothyroidism in pregnancy and hypertensive disorders of pregnancy. Two researchers independently evaluated the quality of all eligible original studies using the Newcastle-Ottawa Scale (NOS). We also performed a meta-analysis using STATA15.1. Sensitivity analyses were also performed by examining the effects of individual studies as well as using different effect models and detecting any publication bias using the harbord test.ResultsTwenty-two studies were included in the final meta-analysis. Our results indicated that pregnant women with subclinical hypothyroidism had an increased risk of HDP (OR = 1.54(95% CI: 1.21-1.96) I²=67.1%), compared with euthyroidism. Subclinical hypothyroidism in pregnancy was not associated with hypertensive disorders of pregnancy at TSH diagnostic cut-off of less than 3.0 mIU/L (P = 0.077). Curiously, the risk of HDP increases when the TSH diagnostic cut-off value is higher or lower than 4 mIU/L. Although only 9 studies were above the threshold, the risk of developing HDP was still 1.69 times, which was highest in all subgroup analyses. This is consistent with the newly recommended diagnostic cut-off value of 4 mIU/L for TSH by the ATA. Our results consider that the risk of hypertensive disorder complicating pregnancy is increased regardless of the diagnosis of subclinical hypothyroidism at any stage of pregnancy. Unfortunately, there is insufficient evidence to support that patients can benefit from treatment with levothyroxine.ConclusionThe results of this meta-analysis indicate that subclinical hypothyroidism in pregnancy is associated with an increased risk of developing HDP, and this association exists regardless of the gestational period. However, the available evidence cannot support these patients receiving thyroxine intervention can benefit from it, so routine screening is only recommended for pregnant women with risk factors for hypothyroidism. Further research is needed to validate more scientific and rigorous clinical studies to clarify the relationship between subclinical hypothyroidism and HDP to improve patient prognosis.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42021286405).

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Subclinical hypothyroidism and cognitive function in people over 60 years: a systematic review and meta-analysis.

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Subclinical hypothyroidism and cognitive function in people over 60 years: a systematic review and meta-analysis.

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