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

## TL;DR

This paper discusses two cases where resistance to thyroid hormone interacts with other thyroid diseases, complicating diagnosis and treatment.

## Contribution

The paper highlights the diagnostic and therapeutic challenges when resistance to thyroid hormone coexists with other thyroid conditions.

## Key findings

- Two patients with RTH and coexisting thyroid disease required complex management due to disrupted physiological compensation.
- Coexisting thyroid conditions can obscure the clinical presentation of RTH, leading to therapeutic challenges.
- Early recognition and personalized management are crucial for optimal outcomes in such cases.

## Abstract

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.