Resistance to Thyroid Hormone Beta and Coexisting Thyroid Disease: Diagnostic and Therapeutic Challenges Illustrated by Two Cases.

Resistance to thyroid hormone (RTH) is a rare clinical syndrome characterized by reduced tissue responsiveness to thyroid hormone (TH), typically presenting with elevated TH levels without suppression of thyrotropin (TSH). In most cases, RTH is caused by mutations in the TH receptor beta (THRB) gene. While treatment is generally unnecessary due to preserved endogenous compensation, this physiological balance may be disrupted in the presence of compromised thyroidal reserve. We report two unrelated female patients with genetically confirmed RTH and coexisting thyroid disease. The first, an 18-year-old with Hashimoto's thyroiditis, required unusually high doses of levothyroxine to maintain TSH within the normal range and was later diagnosed with RTHβ. The second, a 54-year-old with known RTH, developed tachyarrhythmia and amiodarone-induced hypothyroidism, complicating TH replacement. In both cases, the coexistence of RTH and acquired thyroid disease obscured the clinical picture and posed significant therapeutic challenges. These cases illustrate how superimposed thyroid pathology can destabilize the typically compensated state of RTH, underscoring the importance of maintaining a high index of suspicion in patients with persistent, unexplained thyroid function abnormalities. Early recognition, personalized management, and lifelong follow-up are essential to ensure optimal outcomes and avoid unnecessary interventions.