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Cell Metabolism Jun 2017Decreased growth hormone (GH) and thyroid hormone (TH) signaling are associated with longevity and metabolic fitness. The mechanisms underlying these benefits are poorly...
Decreased growth hormone (GH) and thyroid hormone (TH) signaling are associated with longevity and metabolic fitness. The mechanisms underlying these benefits are poorly understood, but may overlap with those of dietary restriction (DR), which imparts similar benefits. Recently we discovered that hydrogen sulfide (HS) is increased upon DR and plays an essential role in mediating DR benefits across evolutionary boundaries. Here we found increased hepatic HS production in long-lived mouse strains of reduced GH and/or TH action, and in a cell-autonomous manner upon serum withdrawal in vitro. Negative regulation of hepatic HS production by GH and TH was additive and occurred via distinct mechanisms, namely direct transcriptional repression of the HS-producing enzyme cystathionine γ-lyase (CGL) by TH, and substrate-level control of HS production by GH. Mice lacking CGL failed to downregulate systemic T metabolism and circulating IGF-1, revealing an essential role for HS in the regulation of key longevity-associated hormones.
Topics: Animals; Cystathionine gamma-Lyase; Dextrothyroxine; Female; Growth Hormone; Hydrogen Sulfide; Hypothalamo-Hypophyseal System; Insulin-Like Growth Factor I; Liver; Mice; Mice, Knockout
PubMed: 28591635
DOI: 10.1016/j.cmet.2017.05.003 -
The Journal of Clinical Endocrinology... Nov 2016Perturbations in thyroid function are common in older individuals but their significance in the very old is not fully understood.
CONTEXT
Perturbations in thyroid function are common in older individuals but their significance in the very old is not fully understood.
OBJECTIVE
This study sought to determine whether thyroid hormone status and variation of thyroid hormones within the reference range correlated with mortality and disability in a cohort of 85-year-olds.
DESIGN
A cohort of 85-year-old individuals were assessed in their own homes (community or institutional care) for health status and thyroid function, and followed for mortality and disability for up to 9 years.
SETTING AND PARTICIPANTS
Six hundred and forty-three 85-year-olds registered with participating general practices in Newcastle and North Tyneside, United Kingdom.
MAIN OUTCOMES
All-cause mortality, cardiovascular mortality, and disability according to thyroid disease status and baseline thyroid hormone parameters (serum TSH, FT, FT, and rT). Models were adjusted for age, sex, education, body mass index, smoking, and disease count.
RESULTS
After adjustment for age and sex, all-cause mortality was associated with baseline serum rT and FT (both P < .001), but not FT or TSH. After additional adjustment for potential confounders, only rT remained significantly associated with mortality (P = .001). Baseline serum TSH and rT predicted future disability trajectories in men and women, respectively.
CONCLUSIONS
Our study is reassuring that individuals age 85 y with both subclinical hypothyroidism and subclinical hyperthyroidism do not have a significantly worse survival over 9 years than their euthyroid peers. However, thyroid function tests did predict disability, with higher serum TSH levels predicting better outcomes. These data strengthen the argument for routine use of age-specific thyroid function reference ranges.
Topics: Aged, 80 and over; Cardiovascular Diseases; Dextrothyroxine; Disabled Persons; England; Female; Humans; Longitudinal Studies; Male; Mortality; Reference Values; Thyroid Diseases; Thyroid Function Tests; Thyrotropin; Triiodothyronine; Triiodothyronine, Reverse
PubMed: 27552542
DOI: 10.1210/jc.2016-1935 -
Endocrinology May 2021The association between thyroid function and dyslipidemia has been well documented in observational studies. However, observational studies are prone to confounding,...
The association between thyroid function and dyslipidemia has been well documented in observational studies. However, observational studies are prone to confounding, making it difficult to conduct causal inference. We performed a 2-sample bidirectional Mendelian randomization (MR) using summary statistics from large-scale genome-wide association studies of thyroid stimulating hormone (TSH), free T4 (FT4), and blood lipids. We chose the inverse variance-weighted (IVW) method for the main analysis, and consolidated results through various sensitivity analyses involving 6 different MR methods under different model specifications. We further conducted genetic correlation analysis and colocalization analysis to deeply reflect the causality. The IVW method showed per 1 SD increase in normal TSH was significantly associated with a 0.048 SD increase in total cholesterol (TC; P < 0.001) and a 0.032 SD increase in low-density lipoprotein cholesterol (LDL; P = 0.021). A 1 SD increase in normal FT4 was significantly associated with a 0.056 SD decrease in TC (P = 0.014) and a 0.072 SD decrease in LDL (P = 0.009). Neither TSH nor FT4 showed causal associations with high-density lipoprotein cholesterol and triglycerides. No significant causal effect of blood lipids on normal TSH or FT4 can be detected. All results were largely consistent when using several alternative MR methods, and were reconfirmed by both genetic correlation analysis and colocalization analysis. Our study suggested that, even within reference range, higher TSH or lower FT4 are causally associated with increased TC and LDL, whereas no reverse causal association can be found.
Topics: Cholesterol, LDL; Cohort Studies; Dextrothyroxine; Dyslipidemias; Genome-Wide Association Study; Humans; Lipids; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Triglycerides
PubMed: 33587120
DOI: 10.1210/endocr/bqab037 -
The Journal of Clinical Endocrinology... Nov 2016The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several... (Meta-Analysis)
Meta-Analysis
CONTEXT
The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously.
DESIGN AND SETTING
We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T, and stroke outcomes were included, and we collected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L.
RESULTS
We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age- and sex-adjusted pooled hazard ratio for TSH was 0.78 (95% confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95% CI 0.62-1.09) for fatal stroke. For the free T analyses, the hazard ratio was 1.08 (95% CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95% CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes.
CONCLUSION
Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dextrothyroxine; Female; Follow-Up Studies; Humans; Male; Middle Aged; Reference Values; Risk; Stroke; Thyrotropin; Young Adult
PubMed: 27603906
DOI: 10.1210/jc.2016-2255 -
Journal of Endocrinological... Sep 2014The aim of the presented study was to evaluate the prevalence of isolated hyperthyrotropinemia (IH) in obese children and the relation between anthropometric and...
PURPOSE
The aim of the presented study was to evaluate the prevalence of isolated hyperthyrotropinemia (IH) in obese children and the relation between anthropometric and metabolic parameters.
METHODS
Hospital records of the children, who presented to the Pediatric Endocrinology outpatient clinic of our institution with obesity, and age and gender-matched healthy children, who had undergone thyroid function test for any reason were retrospectively reviewed.
RESULTS
The prevalence of IH was significantly higher in the obese group than in the controls (9.2 and 3.8 %, respectively). Body mass index-standard deviation score (BMI-SDS), thyroid-stimulating hormone (TSH), lipid parameters were significantly different in the obese group than in the control group. A positive correlation between TSH and BMI-SDS and negative correlation between TSH and free T4 (fT4) levels were found in obese subjects. Stepwise multiple linear regression analysis confirmed that BMI-SDS, fT4 and triglyceride levels were the strongest independent variables correlated with TSH level in obese subjects (r (2) = 0.046, p = 0.001).
CONCLUSIONS
IH prevalence is higher in obese children as compared to healthy children and the increase in TSH level correlates negatively with serum fT4 and positively with BMI-SDS and triglyceride levels in obese children.
Topics: Adolescent; Body Mass Index; Child; Dextrothyroxine; Female; Humans; Male; Pediatric Obesity; Retrospective Studies; Thyroid Function Tests; Thyrotropin; Triglycerides
PubMed: 24920280
DOI: 10.1007/s40618-014-0100-y -
The Journal of Clinical Endocrinology... Nov 2016Although thyroid dysfunction in early pregnancy may have adverse effects on pregnancy outcome and offspring, few prospective studies have evaluated these effects.
CONTEXT
Although thyroid dysfunction in early pregnancy may have adverse effects on pregnancy outcome and offspring, few prospective studies have evaluated these effects.
OBJECTIVE
Our aim was to evaluate the correlations between different thyroid hormone levels in early pregnancy and the incidence of gestational diabetes mellitus (GDM).
SETTING AND PARTICIPANTS
The study comprised 27 513 mothers who provided early pregnancy serum samples for analyses of thyroid function. GDM was diagnosed using a 2 hours, 75-g oral glucose tolerance test, and the mothers were grouped and compared according to the results.
MAIN OUTCOME MEASURES
We focused on GDM during the index pregnancy.
RESULTS
The incidence of GDM in pregnant women tended to increase with age (5.83%, 10.18%, 14.95%, and 22.40%; P < .0001). The incidence of GDM increased with increasing prepregnancy body mass index (P < .0001). Pregnant women with a family history of diabetes had a much higher incidence of GDM than those without a family history of diabetes (21.09% vs 12.92%; P < .0001). The level of free T (FT) in early pregnancy in GDM women was lower than that in non GDM women (P < .0001). With increasing early pregnancy FT, the rate of incident GDM was decreasing (P < .0001).
CONCLUSIONS
Low thyroid hormone levels in early pregnancy are a risk factor for GDM incidence.
Topics: Adult; China; Dextrothyroxine; Diabetes, Gestational; Female; Humans; Pregnancy; Pregnancy Trimester, First; Risk; Young Adult
PubMed: 27583471
DOI: 10.1210/jc.2016-1506