title: 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.
abstract: OBJECTIVE
  The syndrome of resistance to thyroid hormone (RTH) is caused by a mutation of TH receptor β (TRβ) 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 (TSHoma). 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 TSHoma.
  
  
  METHODS
  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 TSHomas.
  
  
  METHODS
  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 TRβ mutation and did not have affected family members. Of these 16 patients, three developed a TSHoma, during follow-up. To distinguish non-TR-RTH from TSHoma, 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 TSHoma.
  
  
  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 TSHoma. It would then be possible to select the patients at higher risk of developing a TSHoma and therefore needing a closer follow-up.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Macchia
authors.forename: Martina
authors.initials: M
authors.lastname: Lombardi
authors.forename: Valentina
authors.initials: V
authors.lastname: Raffaelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Piaggi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Macchia
authors.forename: Ilaria
authors.initials: I
authors.lastname: Scattina
authors.forename: Enio
authors.initials: E
authors.lastname: Martino
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit / Q000097:blood*; D006801:Humans; D006964:Hyperpituitarism / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood* / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*; D055815:Young Adult
chemical_list: D015292:Glycoprotein Hormones, alpha Subunit; D012738:Sex Hormone-Binding Globulin; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013974:Thyroxine