ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Thyroid. 2019;29:480–492.

The thyroid axis is particularly responsive to critical illness. Adaptation processes of the thyroid axis to critical illness and prolonged fasting are well described as non-thyroidal illness syndrome. Non-thyroidal illness is mainly explained by two mechanisms: 1) peripheral inactivation of T4 to rT3 by decreased type-1 deiodinase (DIO1) and increased type-3 deiodinase (DIO3) and 2) if critical illness persists, by central suppression of TSH secretion and resulting decrease of T4.

The current publication was a preplanned secondary analysis of a randomized controlled multicenter study of early versus late parenteral nutritional in infants and children admitted to a pediatric ICU [1]. In this secondary analysis, the authors examined the effect of nutrition on thyroid hormone metabolism during critical illness, including 402 infants and 580 children. First, the authors investigated the prognostic value of non-thyroidal illness at ICU admission.

In multivariable analyses, including thyroid parameters (TSH, T4, T3, rT3 and T3/rT3 ratio) and baseline risk factors (risk of malnutrition, severity of illness by standardized scores), T4 was negatively associated with 90-day mortality and acquisition of new infection during ICU. Second, late parenteral nutrition (starting day 8 after admission) compared to early parenteral nutrition (starting within 24 hours after admission) had beneficial effects on the parameters of peripheral T4 inactivation (fT3 and T3/rT3 ratio) but adverse effects on the parameters of central thyroid regulation (TSH, T4) partly neutralizing the protective effect of late parenteral nutrition.

These data provide new insights into the pathophysiology of non-thyroidal illness and nutrition. As an outlook, the authors suggest to evaluate the effect of TRH to treat the central component of non-thyroidal illness in a randomized controlled study based on their current results and previous data in adults [2].

References: 1. Fivez T, Kerklaan D, Mesotten D, Verbruggen S, Wouters PJ, Vanhorebeek I, Debaveye Y, Vlasselaers D, Desmt L, Caesaer MP, Garcia Guerra G, Hanot J, Joffe A, Tibboel D, Joosten K, van den Berghe G. Early versus late parenteral nutrition in critically ill children. N Engl J Med 2016;374:1111–1122.

2. Van den Berghe G, Wouters P, Weekers F, Mohan S, Baxter RC, Veldhuis JD, Bowers CY, Bouillon R. Reactivation of pituitary hormone release and metabolic improvement by infusion of growth-hormone-releasing peptide and thyrotropin-releasing hormone in patients with protracted critical illness. J Clin Endocrinol Metab 1999;84:1311–1323.