Most thyroid function tests (TFTs) are readily interpretable with thyroid stimulating hormone (TSH) and free T4 +/- free T3 results conforming to well recognised patterns. Occasionally, TFTs may be discordant with the clinical presentation. Biotin is a well-recognised cause of interference in some assays, where patients may be falsely attributed as having hyperthyroidism.
In addition, TFTs may be discordant with elevated free T4 +/- free T3 and non-suppressed TSH, which if not correctly interpreted may lead to inappropriate interventions and patient harm. The differential diagnosis includes biological causes such as TSH secreting pituitary adenoma and thyroid hormone resistance, where early resort to thyroid hormone receptor genotyping can often give a prompt diagnosis and avoid protracted other investigation.
In the first instance, however analytical artefacts should be excluded including heterophilic antibody interference which can be investigated by checking results on an alternative platform and using antibody blocking strategies. Albumin variants (familial dysalbuminaemic hyperthyroxinaemia [FDH]) and also pre-albumin variants can be investigated by mass spectrometry +/- genotyping. Macro-TSH is another cause of discordant TFTs, potentially confounding interpretation.
Close liaison between clinicians and the laboratory is essential for an optimal investigative approach, to avoid potentially inappropriate intervention and to ensure optimal patient outcomes.