Commentary on Normal Thyroid-Stimulating Hormone and Elevated Free Thyroxine in a Patient Presenting with Self-Reported Heart Palpitations

Extract

This diagnostic algorithm describes the investigation of thyroid-stimulating hormone (TSH) in the normal range with an elevated free thyroxine (fT4) and mildly elevated triiodothyronine. A microadenoma of the pituitary was found but excluded as a relevant cause of this presentation as there were no corroborating biochemical features (TSH-omas tend to be invasive macroadenomas). Equilibrium dialysis confirmed the elevated fT4 and analytical interference for TSH measurement was excluded, leaving the suggested diagnosis of resistance to thyroid hormone (RTH) syndrome. RTH syndrome was further confirmed by the targeted sequencing of the THRB gene that identified a heterozygous pathogenic variant on exons 9/10. The “killer” confirmatory information would be if there was a family history, as this condition can be autosomal dominant and may only be retrospectively diagnosed in first-degree relatives; family screening is cost-effective, although the clinical spectrum can vary even among carriers of the same mutation within the same family (1). This variability in clinical manifestations led to the terms “generalized RTH,” applied to those in an euthyroid state, and “pituitary RTH,” with symptoms of thyroid excess. However, this classification is not clinically helpful.