A-076 Re-evaluating the pediatric free thyroxine reference interval: The impact of clinical collaboration

Background Re-evaluation of verified reference intervals (RI) can present challenges with the implementation of upgraded instrumentation from the same vendor. College of American Pathologists requires reevaluation in two instances, when there are notable analytical methodology changes or when the patient population has changed. On the other hand, ISO15189 recommends a more periodic review. While the laboratory is aware of method differences, patient population changes may be less apparent in the absence of a regularly defined review. In such cases, providers may be first to alert the laboratory when a RI may no longer be appropriate. Here, we describe one instance where clinician concern about a shift in free thyroxine (FT4) results and increasing hypothyroidism referrals led to re-evaluation and modification of FT4 RIs in our pediatric population. Methods All pediatric FT4 orders (1-18 years old) with “routine child health examination” ICD-10 codes between new instrumentation go-live in July 2021 and November 2024 (n=890) were retrieved. This data was used to reevaluate a new central 95% RI using a nonparametric analysis (CLSI:C28) in EP Evaluator® (Data Innovations LLC, Colchester, VT). Comparisons between the old, verified RI (CALIPER, 0.80-1.37 ng/dL) and new RI were performed to determine differences in abnormal values. Chart review of patients with abnormally low results within the old RI was also performed to assess the rates of repeat FT4 ordering, send-out testing for FT4 by equilibrium dialysis, and referrals to pediatric endocrinology for low FT4 results. Results A total of 97 pediatric patients (10.9%) had FT4 values below the old RI while only 9 patients (1.0%) had values above this interval. Of the 97 patients with low FT4 results, repeat in-house FT4 testing was performed on 34 patients (35.1%) with additional send-out FT4 equilibrium dialysis testing performed on 13 patients (13.4%). 15 patients (15.5%) were referred to pediatric endocrinology with 2 patients resulting in a new diagnosis of hypothyroidism only. Notably, patients with a lower initial FT4 value were more likely to receive follow-up testing (0.735 ± 0.028 vs. 0.759 ± 0.046 ng/dL; p=0.008). Using the entire wellness pediatric dataset and methods above, the new RI was modified (0.72-1.21 ng/dL; Fig.1). Compared to the old RI, 21 patients (2.4%; net negative, n=76) would have had abnormally decreased FT4 under the new RI with 19 patients (2.1%; net positive, n=10) having abnormally increased FT4. Repeat FT4 testing and Endocrinology referrals were more likely in patients who were still abnormal under this new RI. Most importantly, the 2 patients with new hypothyroidism diagnoses were still abnormally low under the new RI. Conclusion While RI re-evaluation is standard when test methodology changes, understanding when population changes necessitate RI review may be more difficult for the laboratory to appreciate. As such, clinicians may often be the first indicator of when a RI is no longer valid for their patients. Implementation of regular RI review per international standards may better catch when a RI is no longer clinically valid and requires updating.