Defining optimal health range for thyroid function based on the risk of cardiovascular disease.

Chaker, L; Korevaar, T I M; Rizopoulos, D; Collet, T-H; Völzke, H; Hofman, A; Rodondi, Nicolas; Cappola, A R; Peeters, R P; Franco, O H (2017). Defining optimal health range for thyroid function based on the risk of cardiovascular disease. Journal of clinical endocrinology and metabolism, 102(8), pp. 2853-2861. Endocrine Society 10.1210/jc.2017-00410

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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 used as cut-offs for defining and clinically managing thyroid dysfunction.


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

Design and Participants

9,233 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 (2012), which ever came first (689 cases of CVD mortality).

Main Outcomes

We calculated 10-year absolute risks of CVD mortality (defined according to SCORE project) using a Fine and Grey competing risk model per percentile of TSH and FT4, modelled non-linearly and sex- and age-adjusted.


Overall, FT4 > 90th percentile was associated with a predicted 10-year CVD mortality risk >7.5% (p =0.005). In men, FT4 > 97th percentile was associated with a risk of 10.8% (p<0.001). In participants ≥ 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 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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine
04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)

UniBE Contributor:

Rodondi, Nicolas


600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services




Endocrine Society




Doris Kopp Heim

Date Deposited:

23 May 2017 15:52

Last Modified:

24 Oct 2019 11:40

Publisher DOI:


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