ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This large systematic review and individual participant data (IPD) meta-analysis investigated the association between serum TSH and FT4 concentrations and the risk of cardiovascular disease (CVD) events (coronary heart disease, stroke, and heart failure) and all-cause mortality. It included data from 134,346 participants, with a median age of 59 years (range 18-106) and a median follow-up of 11.5 years. The results indicate a J-shaped association between FT4 levels and CVD risk, with the lowest risk observed in the 20th to 40th percentiles of FT4 (13.5–14.8 pmol/L). Higher FT4 levels, particularly above the 85th percentile in women and the 75th percentile in men aged 70 and older, were associated with a more than 5% increase in the 10-year CVD risk. For TSH, the lowest risk was observed in the 60-80th percentiles (1.9–2.9 mIU/L), with both lower and higher TSH levels correlating with increased all-cause mortality.

In a comment in the same October issue of Lancet Diabetes Endocrinol, Elizabeth Pearce stated that “Xu and colleagues provide compelling evidence for working toward a more risk focused approach to defining normal thyroid function” [1]. Although the study by Xu et al certainly had strengths, it also had several limitations, and “adequately powered, long-term trials will be needed to establish age-specific and sex-specific thyroid function test reference ranges based on risk” [1]. An important question for pediatric endocrinologists is what these results mean for thyroid hormone treatment of children. In the treatment of children with severe primary congenital hypothyroidism, relatively high serum FT4 concentrations are often needed to normalize TSH [2].

References: 1. Elizabeth N Pearce. Is it time to re-assess the development of thyroid function reference ranges? Lancet Diabetes Endocrinol. 2023 Oct;11(10):711-712. doi: 10.1016/S2213-8587(23)00257-7. Epub 2023 Sep 8. PMID: 376962742. van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, Cassio A, Heinrichs C, Beauloye V, Pohlenz J, Rodien P, Coutant R, Szinnai G, Murray P, Bartés B, Luton D, Salerno M, de Sanctis L, Vigone M, Krude H, Persani L, Polak M. Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. Thyroid. 2021 Mar;31(3):387-419. doi: 10.1089/thy.2020.0333. PMID: 33272083