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The serum thyroglobulin (Tg), T3, and T4 responses to graded endogenous TSH stimulation were examined in 30 normal subjects for up to 96 h after TRH administration. Increasing TSH rises were elicited by TRH administration as follows: 1) 500 micrograms iv as a single bolus in 10 subjects [mean peak serum TSH, 14.3 +/- 1.8 (SE) microU/ml]; 2) 1000 micrograms infused iv in 2 h in 10 subjects (mean peak TSH, 25.5 +/- 2.6 microU/ml); 3) 40 mg orally in 10 subjects (mean peak TSH, 27.5 +/- 3.0 microU/ml, with a delayed and more prolonged rise). Nine subjects received saline and were used as controls. A significant serum T3 and T4 rise followed the TSH increase in all subjects, and the mean peak value was always reached 4 h after TRH. In contrast, a significant serum Tg increase occurred only in 3, 6, and 9 subjects after 500 micrograms, 1000 micrograms, and 40 mg TRH, respectively. In addition, the time of the Tg peak and its duration was extremely variable but it was always delayed in respect to serum T3 and T4 peaks, occurring 6 to 72 h after TRH administration. No correlation was found between serum Tg and T3 or T4 increases after TRH in any of the three groups. These studies indicate that a significant Tg release in man usually occurs only after intense and prolonged TSH stimulation of the thyroid. In addition, the Tg increase is delayed in respect to the thyroid hormone increase and it is not correlated with them.
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