Thyroid-Stimulating Hormone Immunoassay Interference Presenting as Treatment-Refractory Hypothyroidism: A Case Report

Measurement of thyroid-stimulating hormone (TSH) is fundamental for the diagnosis and therapeutic monitoring of hypothyroidism. Elevated TSH levels, with or without abnormalities in free thyroxine, typically indicate thyroid dysfunction and inform levothyroxine dose adjustments. Although suboptimal TSH control is most commonly attributed to poor medication adherence or improper administration, immunoassay-based TSH measurements are susceptible to analytical interference from sources such as biotin supplementation, heterophile antibodies, and macro-TSH complexes. These interferences may yield misleading biochemical results, potentially resulting in misdiagnosis, unnecessary investigations, and inappropriate escalation of therapy. We describe a case of a 53-year-old woman with persistently elevated TSH despite progressive levothyroxine dose escalation to 2.5 μg/kg/day, initially considered treatment-refractory hypothyroidism. Further evaluation ultimately identified TSH assay interference. This case highlights the importance of considering analytical artifacts when clinical and biochemical findings are discordant.