Elevated free thyroxine and non-suppressed thyrotropin.

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• Thyroid hormone resistance is a rare disorder affecting hormone action.
• Characterized by elevated thyroid hormone levels with normal or elevated TSH.
• Diagnosis can be challenging due to overlapping symptoms with hyperthyroidism.

Observation:

• A young man presented with a 10-year history of elevated free thyroxine (fT4) and non-suppressed thyroid-stimulating hormone (TSH).
• Initial evaluations suggested intermittent hyperthyroidism, but persistent laboratory findings were inconsistent.
• Physical examination revealed a smooth, firm, non-tender goiter.

Findings:

• Laboratory interference was ruled out through serial dilution and alternate assay testing.
• Tests including normal α-subunit, sex hormone binding globulin, partially suppressed TSH by triiodothyronine (T3), and TSH response to thyrotropin-releasing hormone (TRH) supported resistance to thyroid hormone syndrome.
• Genetic sequencing identified a heterozygous R320L mutation in the thyroid hormone receptor-β gene, confirming the diagnosis by demonstrating reduced T3 affinity and corepressor dissociation.

Implications:

• This case highlights the importance of considering rare genetic disorders in persistent thyroid dysfunction.
• Genetic confirmation is crucial for accurate diagnosis of resistance to thyroid hormone syndrome.
• Understanding the molecular basis of mutations aids in comprehending thyroid hormone signaling pathways.