@article {6798, title = {Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts.}, journal = {JAMA Intern Med}, volume = {175}, year = {2015}, month = {2015 Jun}, pages = {1037-47}, abstract = {

IMPORTANCE: Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD).

OBJECTIVE: To assess the association between differences in thyroid function within the reference range and CHD risk.

DESIGN, SETTING, AND PARTICIPANTS: Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline.

EXPOSURES: Thyroid function as expressed by serum thyrotropin levels at baseline.

MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status.

RESULTS: Among 55,412 individuals, 1813 people (3.3\%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5\%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95\% CI, 0.90-1.04) for CHD mortality and 1.00 (95\% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95\% CI, 0.74-1.20]) and CHD events (0.97 [95\% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results.

CONCLUSIONS AND RELEVANCE: Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

}, keywords = {Cohort Studies, Coronary Disease, Humans, Hypothyroidism, Thyrotropin}, issn = {2168-6114}, doi = {10.1001/jamainternmed.2015.0930}, author = {Asvold, Bj{\o}rn O and Vatten, Lars J and Bj{\o}ro, Trine and Bauer, Douglas C and Bremner, Alexandra and Cappola, Anne R and Ceresini, Graziano and den Elzen, Wendy P J and Ferrucci, Luigi and Franco, Oscar H and Franklyn, Jayne A and Gussekloo, Jacobijn and Iervasi, Giorgio and Imaizumi, Misa and Kearney, Patricia M and Khaw, Kay-Tee and Maciel, Rui M B and Newman, Anne B and Peeters, Robin P and Psaty, Bruce M and Razvi, Salman and Sgarbi, Jos{\'e} A and Stott, David J and Trompet, Stella and Vanderpump, Mark P J and V{\"o}lzke, Henry and Walsh, John P and Westendorp, Rudi G J and Rodondi, Nicolas} } @article {7805, title = {Low thyroid function is not associated with an accelerated deterioration in renal function.}, journal = {Nephrol Dial Transplant}, year = {2018}, month = {2018 Apr 18}, abstract = {

Background: Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups.

Methods: Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models.

Results: A total of 72~856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95\% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66~542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329~713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function.

Conclusions: Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

}, issn = {1460-2385}, doi = {10.1093/ndt/gfy071}, author = {Meuwese, Christiaan L and van Diepen, Merel and Cappola, Anne R and Sarnak, Mark J and Shlipak, Michael G and Bauer, Douglas C and Fried, Linda P and Iacoviello, Massimo and Vaes, Bert and Degryse, Jean and Khaw, Kay-Tee and Luben, Robert N and Asvold, Bj{\o}rn O and Bj{\o}ro, Trine and Vatten, Lars J and de Craen, Anton J M and Trompet, Stella and Iervasi, Giorgio and Molinaro, Sabrina and Ceresini, Graziano and Ferrucci, Luigi and Dullaart, Robin P F and Bakker, Stephan J L and Jukema, J Wouter and Kearney, Patricia M and Stott, David J and Peeters, Robin P and Franco, Oscar H and V{\"o}lzke, Henry and Walsh, John P and Bremner, Alexandra and Sgarbi, Jos{\'e} A and Maciel, Rui M B and Imaizumi, Misa and Ohishi, Waka and Dekker, Friedo W and Rodondi, Nicolas and Gussekloo, Jacobijn and den Elzen, Wendy P J} }