Variable thyrotropin response to thyrotropin-releasing hormone after small decreases in plasma free thyroid hormone concentrations in patients with nonthyroidal diseases

Although a normal serum thyrotropin (TSH) concentration is generally considered to be the most important finding to support the clinical impression of euthyroidism in patients with nonthyroidal diseases and decreased serum triiodothyronine (T₃), the regulation of TSH secretion in sick patients has not been studied previously. Accordingly, we studied the regulation of TSH secretion in 23 patients with nonthyroidal diseases; 15 of the patients had decreased serum T₃. TSH regulation was studied by measuring the TSH response to injected thyrotropin-releasing hormone (TRH) before and after effecting a small decrease in serum thyroxine (T₄) and/or T₃ concentrations by iodide treatment, 262 mg daily for 10 d. Iodide treatment significantly decreased (> 10%) the free T₄ index (FT₄-I) and/or free T₃ index FT₃-I) in all patients. FT₄-I values were correlated (0.611, P < 0.001), with free T₄ concentration determined by equilibrium dialysis. Despite decreased FT₄-I and/or FT₃-I after iodide treatment in all patients, the TSH response to TRH after iodide treatment was augmented in only 8 of 15 patients who had decreased serum T₃ (group 1) and in only 5 of 8 patients who had a normal serum T₃. Mean base-line TSH concentration was increased significantly (P < 0.05) from 0.9 ± to 1.5 ± 0.3 μU/ml in group 1 only. Comparison of the mean TSH response to TRH showed that there was no significant difference between groups 1 and 2. Moreover, no significant difference in thyroidal parameters was observed between patients who had augmented TSH response to TRH after iodides and those who had either similar or decreased TSH response irrespective of the initial serum T₃. These studies show that an augmented TSH response to TRH in response to a small reduction in serum T₄ and T₃ concentration occurred in only 57% of the entire group of patients with nonthyroidal diseases and that the presence or absence of a normal TSH response to this stimulus did not seem to be related to the base-line serum T₃ concentration. Because an increase in serum TSH in response to decreased serum T₄ and T₃ did not occur in about one-half of patients with nonthyroidal diseases, normal serum TSH may not be a reliable index of the euthyroid state in these patients.