Approach to the patient with raised thyroid hormones and non-suppressed TSH.

Measurement of free thyroid hormones (TH) and thyrotropin (TSH) using automated immunoassays is central to the diagnosis of thyroid dysfunction. Using illustrative cases, we describe a diagnostic approach to discordant thyroid function tests, focusing on entities causing elevated free thyroxine (FT4) and/or free triiodothyronine (FT3) measurements with non-suppressed TSH levels. Different types of analytical interference (e.g. abnormal thyroid hormone binding proteins, antibodies to iodothyronines or TSH, heterophile antibodies, biotin) or disorders (e.g. Resistance to Thyroid Hormone β or α, monocarboxylate transporter 8 or selenoprotein deficiency, TSH-secreting pituitary tumour) that can cause this biochemical pattern will be considered. We show that a structured approach, combining clinical assessment with additional laboratory investigations to exclude assay artefact, followed by genetic testing or specialised imaging, can establish a correct diagnosis, potentially preventing unnecessary investigation or inappropriate therapy.