Endocrine Abstracts

Background: Thyroid stimulating hormone (TSH) and free T4 (fT4) were requested on a neonate, on Day 1 after birth. fT4 was flagged as below range, TSH was insufficient for analysis. Day 5-8 newborn bloodspot screening flagged a high TSH, hypothyroidism was confirmed, and thyroxine treatment commenced. Internal investigation into the incident, and the potential impact on the baby of delayed onset of treatment, raised the question of the relevance of our reference intervals (RI) in neonates. Agreed action was to implement evidence-based paediatric RI for TSH, fT4 and free T3 (fT3). Following implementation of Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) RI’s, referrals to paediatric endocrinology services from primary care for investigation of hypothyroidism, on the basis of a low fT4, soared. Hence, we sought to establish our own lower limit of normal (LLN) for our RI for fT4.

Methods: Paediatric primary care TSH and fT4 results, between ages 1-18yr (368), were assessed between Jan-2020 and May-2022. Only fT4 results with TSH within the RI were included (201). Kolmogorov-Smirnov test showed non-normal fT4 distribution (skewness 0.8; kurtosis 1.09). LLN was calculated using bootstrapped (N+1)p quantiles.

Results: Introduction of the CALIPER fT4 range for our method and instrument (11.4 – 17.6 pmol/l) involved a dramatic shift in LLN from our adult range (9.0 – 19.1 pmol/l). In a population of Norfolk children, the calculated LLN was substantially lower, providing the range 9.3 – 17.6 pmol/l. Implementation of this new LLN for fT4 resulted in a dramatic reduction of inappropriate referrals for hypothyroidism from primary care from healthy children.

Conclusions: CALIPER RI are an invaluable resource for laboratory medicine, but care must be taken in implementing these without due consideration of the applicability to your local population, and the potential impact on secondary care services.