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J Clin Endocrinol Metab. 2017 Aug 1;102(8):2853-2861. doi: 10.1210/jc.2017-00410.

Defining Optimal Health Range for Thyroid Function Based on the Risk of Cardiovascular Disease.

Author information

Academic Center for Thyroid Diseases, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
Department of Epidemiology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
Department of Biostatistics, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
Service of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne, CH-1015 Lausanne, Switzerland.
Institute for Community Medicine, Clinical-Epidemiological Research/SHIP, University Medicine, Greifswald and German Centre of Cardiovascular Research, Partner Site, 17489 Greifswald, Germany.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115.
Department of General Internal Medicine, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.
Institute of Primary Health Care (BIHAM), University of Bern, 3010 Bern, Switzerland.
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.



Reference ranges of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are defined by their distribution in apparently healthy populations (2.5th and 97.5th percentiles), irrespective of disease risk, and are used as cutoffs for defining and clinically managing thyroid dysfunction.


To provide proof of concept in defining optimal health ranges of thyroid function based on cardiovascular disease (CVD) mortality risk.

Design and Participants:

In all, 9233 participants from the Rotterdam Study (mean age, 65.0 years) were followed up (median, 8.8 years) from baseline to date of death or end of follow-up period (2012), whichever came first (689 cases of CVD mortality).

Main Outcomes:

We calculated 10-year absolute risks of CVD mortality (defined according to the SCORE project) using a Fine and Gray competing risk model per percentiles of TSH and FT4, modeled nonlinearly and with sex and age adjustments.


Overall, FT4 level >90th percentile was associated with a predicted 10-year CVD mortality risk >7.5% (P = 0.005). In men, FT4 level >97th percentile was associated with a risk of 10.8% (P < 0.001). In participants aged ≥65 years, absolute risk estimates were <10.0% below the 30th percentile (∼14.5 pmol/L or 1.10 ng/dL) and ≥15.0% above the 97th percentile of FT4 (∼22 pmol/L or 1.70 ng/dL).


We describe absolute 10-year CVD mortality risks according to thyroid function (TSH and FT4) and suggest that optimal health ranges for thyroid function can be defined according to disease risk and are possibly sex and age dependent. These results need to be replicated with sufficient samples and representative populations.

[Indexed for MEDLINE]

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