Introduction: Resistance to thyroid hormone (TH) can be caused by a failure of TH to enter the cell, or by a lack of action of intracellular TH.
Cases: Patient A, a 60-year-old man, presented with an elevated TSH (15.8 mU/l (reference range: 0.44.3 mU/l)), an elevated FT4 (29.5 pmol/l (1125 pmol/l)), and a normal T3. Reverse T3 (rT3), the inactive metabolite of T4, was clearly elevated (0.82 nmol/l (0.140.34 nmol/l)). His medical history revealed a partial thyroidectomy because of hyperthyroidism. After disease recurrence, he was treated with radioactive iodine in 2001. At presentation, he used 75 μg of thyroxine daily. Additional evaluation showed no signs of TH dysfunction, and other hormonal axes functioned normally. The differential diagnosis consisted of resistance to TH, a TSH producing tumor, or an altered TH transporter or metabolizing enzyme. We identified a novel mutation in TRβ (Leu456Phe), which was not found in his family members. The effect of the Leu456Phe mutation is currently being tested.
Patient B, a 33-year-old man, presented with an elevated FT4 (42.1 pmol/l), an elevated T3 (3.16 nmol/l (1.42.5 nmol/l)), and an elevated rT3 (0.72 nmol/l). Nevertheless, he had a non-suppressed TSH (3.31 mU/l) and no symptoms of hyperthyroidism. Additional laboratory testing showed normal function of other hormonal axes, and a normal TRH-test. His mother and aunt had elevated levels of FT4 and a non-suppressed TSH as well, and one of them had an increased metabolic rate. Genetic testing revealed a mutation in TRβ (Glu462Lys) in all three subjects. This mutation was previously described in three unrelated families, resulting in a similar phenotype.
Conclusion: We identified two different mutations in TRβ, resulting in TH resistance in four subjects. High levels of TH, a normal or slightly elevated TSH, and usually mild symptoms are suggestive for the diagnosis.
03 - 07 May 2008
European Society of Endocrinology