Since the introduction of 3rd generation TSH assay methods, TRH testing remains essential only in a few limited areas. However, for these same authors, the application of ultrasensitive tests in conjunction with the TRH test has not yet been fully evaluated as some authors note. The thyroid cell has a potent and active deiodase in the normal subject explaining the strong correlation between T4 and TSH. An inter-individual variability of the activity of this deiodase enzyme is very conceivable considering the genetic polymorphism. We prospectively studied and determined in a homogeneous population of patients with treated peripheral hypothyroidism, a real overdose by an abolished response of the immunoradiometric TSH of first generation, to TRH and specify the optimal doses of levothyroxine (LT4) in this thyroid hormone replacement therapy