Differential diagnosis between autoimmune thyrotoxicosis and thyroid hormone resistance syndrome: clinical case report

We report a case of 50-year-old woman with thyroid hormone resistance syndrome. For 20 years this patient have been treated for autoimmune thyrotoxicosis: she underwent thyroid surgery and then was on thyroid-blocking therapy. Repeated laboratory tests demonstrated elevated serum thyroid hormones concentrations and elevated TSH concentration. Inappropriate TSH secretion became the reason for conducting further investigations. In those cases, the diagnostic approach is complicated and cases may be referred as a syndrome of thyroid hormones resistance or as a pituitary mass. Results of magnetic resonance imaging as well as results of octreotide test did not confirm TSH-producing pituitary adenoma. Lack of consistent thyrotoxicosis symptoms and normal level of biochemical markers that reflect peripheral tissue response to excessive thyroid hormones action were regarded as an evidence for thyroid hormones resistance syndrome. In cases of thyroid hormone resistance syndrome, there is no reduction in thyroid hormones after octreotide administration and we could observe it in our patient. Thereby clinical data and laboratory tests supported the diagnosis of thyroid hormone resistance syndrome. To establish definitive diagnosis and to verify genetic cause of the disease we performed direct sequencing of the THRB gene exons 910.

The Mutant Thyroid Hormone Receptor Beta R320P Causes Syndrome of Resistance to Thyroid Hormone

A 31-year-old Japanese male patient with a history of atrial fibrillation showed elevated serum levels of free thyroxine and triiodothyronine and a normal level of thyrotropin. The same abnormal hormone pattern was also found in his son. These data indicated that the index patient and the son have thyroid hormone resistance syndrome. Exon sequencing using DNA from these two patients revealed that both patients harbored a heterozygous mutation in the THRB gene: G1244C in exon 9, which results in R320P substitution. Therefore, thyroid hormone resistance syndrome caused by THRB mutation (RTHβ) was diagnosed. The mutation of the 320th arginine to proline has not been found to date. In conclusion, herein, we have described the first case of RTHβ that is associated with R320P mutation.