Pituitary-Thyroid Hormone Economy in Healthy Aging Men: Basal Indices of Thyroid Function and Thyrotropin Responses to Constant Infusions of Thyrotropin Releasing Hormone*

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Abstract
In order to assess the effects of aging, as distinct from those of thyroid disease or extrathyroidal illness, on certain indices of thyroid function, we studied 74 healthy, ambulatory men recruited from the Baltimore Longitudinal Study on Aging. We determined basal serum values of T4, T3. rT3, thyroxinebinding globulin (TBG), and T3 resin uptake (T3RU) and calculated the free T4 index (FT4I=T4 × T3RU/100), free T3 index (FT3I = T3 × T3RU/100), and T4/TBG ratio for each subject. We used an ultrasensitive RIA to measure variations in basal concentrations of TSH within the normal range. We then infused TRH at a constant rate (0.4 αg/min iv) for 240 min into 63 of the same men; serum samples, collected at 15-min intervals during the infusion, were analyzed for TSH by routine RIA. Subjects were divided into 3 groups according to age; A (n = 26, mean age = 39.4), B (n = 23, mean age = 60.0), and C (n = 25, mean age = 79.6). Analysis of variance with Duncan’s multiple range test and regression analysis were used to evaluate data. There was no significant (P > 0.05) variation with age of basal serum values of T4, TBG, or T3RU. Comparison of groups A and C showed significant decreases of mean values of serum T3 (−11%, P < 0.05), FT3I(-13%, P = 0.02), FT4I (−11%, P < 0.01), and T4/TBG ratio (−12%, P < 0.01) and an increase in serum TSH (+ 38%, P< 0.05). For these variables, the mean values for group B were intermediate between, but not significantly different from, those of A and C. Regression analysis showed significant correlations of age with T3, FT3I, FT4I, T4/ TBG, and TSH at P levels similar to those obtained by Duncan’s test. No elderly individual exhibited a baseline elevation of TSH (>7 µU/ml) or depression of T4 (< µg/dl), suggesting that primary hypothyroidism was not present in our old group. The basal TSH concentration did not correlate significantly with any index of thyroid function except with FT3I in group C (r = −0.43, P < 0.05). In all age groups the TSH responses to TRH exhibited a biphasic pattern with early and late peaks. The magnitudes and timing of early and late peaks, peak increments, fractional responses, and integrated areas under the response curves were similar among age groups. We conclude that a small but significant decrease in serum T3 concentrations is a concomitant of normal aging in men. A slight increase in serum hormone binding rendered the decrease of FT3I more prominent than that of total T3. The increased protein binding also combined with modest decrements in total T4 to produce significantly reduced FT4I. The absence of augmented TSH responses to TRH infusion, despite a small but significant increase in basal TSH concentration, may indicate that there is an age-related diminution in function of pituitary thyrotropes.

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