Clinical and genetic characteristics of a large monocentric series of patients affected by thyroid hormone (Th) resistance and suggestions for differential diagnosis in patients without mutation of Th receptor β

Summary Objective The syndrome of resistance to thyroid hormone ( RTH ) is caused by a mutation of TH receptor β ( TR β) in 80% of cases. Patients without mutation (non‐ TR ‐ RTH ) may have a biochemical pattern that is difficult to differentiate from that of pituitary TSH ‐secreting adenoma ( TSH oma). Herein, we report a large monocentric series of RTH focusing on patients with non‐ TR ‐ RTH , to evaluate possible clinical or biochemical parameters able to distinguish them from TSH oma. Design and patients We retrospectively reviewed the data of 99 consecutive patients with inappropriate TSH secretion ( IST ) syndrome referred to our Department between 1983 and 2011, identifying 68 patients with RTH and 31 patients with TSH omas. Measurements Patient records were reviewed for the main clinical, biochemical and imaging characteristics. Results Of our 68 patients with RTH , 16 (23·5%) did not show a TR β mutation and did not have affected family members. Of these 16 patients, three developed a TSH oma, during follow‐up. To distinguish non‐ TR ‐ RTH from TSH oma, we identified appropriate cut‐off values for the main biochemical parameters that demonstrated the greatest sensitivity and specificity (T3 suppression test, α‐subunit/ TSH molar ratio, α‐subunit assay and TRH test) and we calculated the probability for each patient to develop a TSH oma. Conclusions The application of the identified cut‐offs could become a very useful tool in the challenging differential diagnosis between sporadic non‐ TR ‐ RTH and TSH oma. It would then be possible to select the patients at higher risk of developing a TSH oma and therefore needing a closer follow‐up.