SAT-394 - Resistance to Thyroid Hormone β Presenting as Discordant Thyroid Function Tests: A Diagnostic Challenge

Background:
Resistance to thyroid hormone (RTH) is a rare autosomal dominant disorder characterized by reduced tissue responsiveness to thyroid hormone, typically presenting with elevated free T4 and T3 levels with non-suppressed TSH. Misdiagnosis as hyperthyroidism can lead to inappropriate treatment.

Case Presentation:
A 41-year-old woman with a history of iron deficiency anemia presented with fatigue and abnormal thyroid function tests. Laboratory evaluation revealed persistently elevated free T4 (2.06–2.38 ng/dL) with non-suppressed TSH (2.9–5.48 µIU/mL) and high-normal T3 levels. She denied exogenous thyroid hormone use. Thyroid antibodies were negative. Ultrasound showed multinodular goiter.

Given discordant thyroid function tests, assay interference and central causes were evaluated. Equilibrium dialysis confirmed elevated free T4 (2.6 ng/dL), supporting a true biochemical abnormality. Pituitary workup, including normal alpha-subunit levels, made TSH-secreting adenoma unlikely. Genetic testing revealed a heterozygous THRB gene variant (c.1147C>T; p.Arg383Cys), classified as a variant of uncertain significance.

Based on clinical, biochemical, and genetic findings, a diagnosis of RTHβ was made. The patient was managed conservatively with monitoring and planned family screening.

Discussion:
RTHβ should be considered in patients with elevated thyroid hormones and non-suppressed TSH after excluding assay interference and exogenous hormone use. This case highlights the diagnostic value of equilibrium dialysis in confirming true hormone elevation and demonstrates that genetic variants, even of uncertain significance, can support diagnosis when interpreted in clinical context.

Conclusion:
A systematic approach is essential in evaluating discordant thyroid function tests. Early use of equilibrium dialysis and consideration of RTHβ can prevent misdiagnosis and inappropriate treatment. Genetic testing plays a key role in confirming diagnosis and guiding family evaluation.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*