ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab. 2020;105:dgaa415. doi: 10.1210/clinem/dgaa415.

The optimal cut-off for neonatal screening has long been a matter of debate. The optimal balance between optimal detection of cases and increase of false positive patients is difficult to define. Also, in the most recent guidelines for congenital hypothyroidism (see previous paper in this chapter 3.7), no precise cut-off was recommended, as screening approaches differ considerably [1].

West et al. addressed this open question by a retrospective study. They analysed the long-term neurodevelopmental outcome of 96 healthy individuals who passed routine neonatal screening according to the 15 mU/l TSH cut-off. They had a neonatal screening TSH of 8–14 mU/l. At age 6–12 years, these individuals and 76 siblings were investigated by Wechsler Intelligence Scale for Children. The study was powered to detect differences of 5 IQ points or more between cases and siblings.

Lower mid-childhood IQ showed a mild correlation with increasing TSH levels <15 mU/l. However, if IQ was compared between cases and siblings, no difference was detected over the whole TSH-range of 8–14 mU/l. The authors conclude that there was no clinically relevant long-term negative effect when screening cut-off is 15 mU/l. They argue against lowering the neonatal screening cut-off to below 15 mU/l.

This study is of importance in a field where long-term data are scarce. The study was well designed and limitations discussed in detail. As also discussed by the authors, it is noteworthy that 80% (53/67) of cases with available siblings included had a TSH of 8–11 mU/l, while only 20% (13/67) of cases with siblings had a TSH value between 12–14 mU/l rendering the data more robust in the lower range of TSH values below ≤11 mU/l, where 12-14 case-sibling pairs could be compared for each additional unit of TSH. Nevertheless, these data add information on a TSH range, where also previous studies included only few cases. [2]. Ultimately, only prospective studies of treated versus untreated patients will provide robust evidence for the optimal TSH screening cut-off.

Reference: 1. 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. 2021:387–419. doi: 10.1089/thy.2020.0333.2. Trumpff C, De Schepper J, Vanderfaeillie J, Vercruysse N, Van Oyen H, Moreno-Reyes R, Tafforeau J, Vandevijvere S. Neonatal thyroid-stimulating hormone concentration and psychomotor development at preschool age. Arch Dis Child. 2016 Dec;101(12):1100–1106. doi: 10.1136/archdischild-2015-310006.