Variable thyrotropin response to thyrotropin-releasing hormone after small decreases in plasma thyroid hormone concentrations in patients of advanced age

It was recently reported that TSH regulation was abnormal in 50% of patients hospitalized for nonthyroidal diseases because the TSH response to TRH was not augmented following an iodide-induced small decrease in serum T₄ and T₃ concentrations. Since the mean age of that group was 65.0 years, we considered the possibility that some of the findings of that study were due to the advanced age of the patients in addition to the presence of nonthyroidal illness. Accordingly, some aspects of TSH regulation in 24 outpatients of advanced age followed for routine health maintenance have now been studied; eight young adults (28-49 years of age) were studied as controls. Six patients were between 60 and 69 years of age, nine were between 70 and 79 years of age, and nine were between 80 and 89 years of age. TSH regulation was studied by measuring the TSH response to injected thyrotropin-releasing hormone (TRH) before and after a small decrease in plasma thyroid hormone concentrations had been produced by a 10-day treatment course with iodides (262 mg/d). Iodide treatment resulted in a 10% or greater decrease in serum T₄, FT₄, or T₃ levels in 20 of the 24 patients. A significant decrease in the mean plasma T₄ level from 7.6 ± 0.5 μg/dL to 6.7 ± 0.4 μg/dL (P < 0.01) was noted; however, the decrease in the mean plasma T₃ level from 116 ± 5 ng/dL to 110 ± 4 ng/dL was significant only at the P < 0.1 > 0.05 level. No major difference in the mean T₄, FT₄, or T₃ levels or the integrated TSH response to TRH were observed between the men (13) and women (11) in the different age groups except in the 70-79-year-old group, in which the integrated TSH response of the men was decreased. Iodide treatment did not affect basal plasma TSH levels but the mean integrated TSH response to TRH was increased from 801 ± 123 μU·min to 996 ± 135 μU·min (P < 0.025). In contrast to this modest increase, a mean 137% increase in the integrated TSH response to TRH was noted in the control subjects (28-49 years old), who exhibited a similar decrease in serum T₄ and T₃ levels after iodide treatment. Whereas the TSH response to TRH after iodide treatment was augmented in all of the younger control subjects, only 9 of the 20 aged patients who responded to iodide treatment had normal TSH responsiveness. There was no significant age or sex difference between the TSH responders and nonresponders. Similarly, there was no significant difference between the mean plasma T₄, FT₄, and TSH levels between these groups; the mean plasma T₃ level in the TSH responsive group, 103 ± 4 ng/dL, wss significantly lower than that of the TSH nonresponders, 128 ± 7 ng/dL. Because the anticipated increase in plasma TSH in response to a small decrease in T₄, FT₄, or T₃ occurred in less than one-half of patients of advanced age, a normal plasma TSH level may not be a reliable index of the euthyroid state in aged patients.