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.
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