Resistance to Thyroid Hormone Beta or Thyroid-Stimulating Hormone (TSH)-Secreting Pituitary Adenoma: A Diagnostic Dilemma With a THRB Variant of Uncertain Significance

Elevated thyroid hormone concentrations with nonsuppressed thyroid-stimulating hormone (TSH) present a challenging diagnostic problem.Resistance to thyroid hormone beta (RTHβ), analytical interference, and a TSH-secreting pituitary adenoma (TSHoma) are important considerations.We describe a woman with persistent elevation of free thyroxine (FT4) and nonsuppressed or elevated TSH for more than five years, autoimmune thyroiditis, a heterozygous THRB c.284G>C (p.Gly95Ala) variant classified as a variant of uncertain significance (VUS), and a 4.9 × 4.4 mm pituitary microadenoma.Human anti-mouse antibody testing was negative, and subsequent free alpha-subunit measurement was within the reference range.The biochemical phenotype was compatible with RTHβ, but the VUS could not establish a molecular diagnosis, while the pituitary lesion could not be assumed to be causal.This case highlights the risk of diagnostic anchoring when genomic and imaging abnormalities coexist and emphasizes integrating longitudinal biochemistry, assay evaluation, molecular classification, and pituitary assessment before diagnosing RTHβ or TSHoma.