Suspected Resistance to Exogenous Thyroxine in an Elderly Man: Case Review and Comparison with SORSHOT

Resistance to exogenous thyroxine (RETH) has recently been proposed as a condition characterized by persistent hyperthyrotropinemia despite levothyroxine (LT4) replacement therapy. However, cases involving elderly patients have rarely been reported. We describe an elderly male patient with suspected RETH and discuss his clinical characteristics in comparison with syndrome of residual symptoms of hypothyroidism on T4 (SORSHOT). A 79-year-old man with primary hypothyroidism secondary to cervical irradiation presented with persistent elevation of thyroid-stimulating hormone (TSH) despite LT4 replacement monotherapy. Increasing the LT4 dose improved biochemical hypothyroidism but repeatedly induced chest discomfort and general fatigue, thereby limiting adequate dose escalation. Comparative analysis using 8,183 paired TSH and free thyroxine (FT4) measurements demonstrated disproportionately elevated TSH levels relative to FT4 concentrations. Macro-TSH was excluded using polyethylene glycol precipitation and gel filtration chromatography. Genetic analyses of THRB and TSHR revealed no pathogenic variants. Because persistent hyperthyrotropinemia remained unexplained and the clinical course was compatible with previously reported features of RETH, liothyronine (LT3) was added to LT4 therapy. After LT3 administration, TSH decreased to near the upper limit of the reference range without worsening subjective symptoms. We previously reported a similar elderly patient with suspected RETH. The clinical characteristics of RETH and its similarities and differences with SORSHOT are discussed, particularly from the perspective of impaired T4-to-T3 conversion and decreased thyroid volume.