@article {6795, title = {Subclinical thyroid dysfunction and fracture risk: a meta-analysis.}, journal = {JAMA}, volume = {313}, year = {2015}, month = {2015 May 26}, pages = {2055-65}, abstract = {

IMPORTANCE: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking.

OBJECTIVE: To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures.

DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures.

DATA EXTRACTION: Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH >=4.50-19.99 mIU/L) with normal thyroxine concentrations.

MAIN OUTCOME AND MEASURES: The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes.

RESULTS: Among 70,298 participants, 4092 (5.8\%) had subclinical hypothyroidism and 2219 (3.2\%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6\%; 12 studies), any fracture in 2528 participants (9.0\%; 8 studies), nonspine fracture in 2018 participants (8.4\%; 8 studies), and spine fracture in 296 participants (1.3\%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95\% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95\% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95\% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95\% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95\% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95\% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95\% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95\% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95\% CI, 1.19-1.93) for hip fracture, 1.42 (95\% CI, 1.16-1.74) for any fracture, and 1.74 (95\% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk.

CONCLUSIONS AND RELEVANCE: Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Female, Fractures, Bone, Hip Fractures, Humans, Hyperthyroidism, Hypothyroidism, Male, Middle Aged, Risk Factors, Spinal Fractures, Thyrotropin, Young Adult}, issn = {1538-3598}, doi = {10.1001/jama.2015.5161}, author = {Blum, Manuel R and Bauer, Douglas C and Collet, Tinh-Hai and Fink, Howard A and Cappola, Anne R and da Costa, Bruno R and Wirth, Christina D and Peeters, Robin P and Asvold, Bj{\o}rn O and den Elzen, Wendy P J and Luben, Robert N and Imaizumi, Misa and Bremner, Alexandra P and Gogakos, Apostolos and Eastell, Richard and Kearney, Patricia M and Strotmeyer, Elsa S and Wallace, Erin R and Hoff, Mari and Ceresini, Graziano and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Stott, David J and Westendorp, Rudi G J and Khaw, Kay-Tee and Langhammer, Arnuf and Ferrucci, Luigi and Gussekloo, Jacobijn and Williams, Graham R and Walsh, John P and J{\"u}ni, Peter and Aujesky, Drahomir and Rodondi, Nicolas} } @article {7550, title = {Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.}, journal = {Circulation}, volume = {136}, year = {2017}, month = {2017 Nov 28}, pages = {2100-2116}, abstract = {

BACKGROUND: Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.

METHODS: We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.

RESULTS: Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5\%) had subclinical hypothyroidism and 2574 individuals (8.6\%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95\% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend <=0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.

CONCLUSIONS: In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

}, keywords = {Adult, Aged, Aged, 80 and over, Asymptomatic Diseases, Atrial Fibrillation, Biomarkers, Chi-Square Distribution, Female, Humans, Hypothyroidism, Incidence, Male, Middle Aged, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine, Time Factors, Young Adult}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.117.028753}, author = {Baumgartner, Christine and da Costa, Bruno R and Collet, Tinh-Hai and Feller, Martin and Floriani, Carmen and Bauer, Douglas C and Cappola, Anne R and Heckbert, Susan R and Ceresini, Graziano and Gussekloo, Jacobijn and den Elzen, Wendy P J and Peeters, Robin P and Luben, Robert and V{\"o}lzke, Henry and D{\"o}rr, Marcus and Walsh, John P and Bremner, Alexandra and Iacoviello, Massimo and Macfarlane, Peter and Heeringa, Jan and Stott, David J and Westendorp, Rudi G J and Khaw, Kay-Tee and Magnani, Jared W and Aujesky, Drahomir and Rodondi, Nicolas} }