Response to thyrotropin releasing hormone: An objective criterion for the adequacy of thyrotropin suppression therapy

Most serum thyrotropin (TSH) assays do not adequately discriminate between normal values and absent TSH. We therefore evaluated the TSH response to thyrotropin releasing hormone (TRH) as a criterion for the adequacy of TSH suppression therapy. Twenty-six outpatients with various thyroid disorders (cancer, 10; nodules, 9; miscellaneous, 4; hypothyroidism after¹³¹I therapy for Graves' disease, 3) were studied. Using the frequent sampling technique (samples every 20 min) in two normal volunteers and one untreated patient who was TRH-responsive, we first confirmed the observation that TSH secretion occurred episodically throughout the 24-h period. In contrast, serum TSH was undetectable (<0.6 μU/ml) throughout the 24-h period in 5 patients on TSH suppression therapy who were TRH-unresponsive and one who had a minimal response to TRH. Thus, TRH-unresponsive patients did not secrete measurable amounts of TSH throughout the 24-h period. To suppress TSH secretion, all patients were treated with L-thyroxine (T₄) at doses which resulted in undetectable TSH values in random plasma samples. TRH tests were carried out only when random TSH concentrations were <0.6 μU/ml. Seven of the twenty-six patients (27%) including two with thyroid cancer were TRH-responsive indicating a potential for TSH secretion. In these seven, the T₄ dose was adjusted until they were TRH-unresponsive. The mean change in T₄ dose of these 7 patients was 20 ± 10 (SD) /μg/day and this resulted in a mean increase of 1.5 ± 1.1 μg/dl for T₄ and 20 ± 20 ng/dl for T₃. For all patients, the mean T4 dose required for TSH suppression was 172 ± 53 μg/ day or 2.6 ± 0.8 μg per day per kg body weight. Twenty-three of 26 patients required between 100-200 μg/day and the remaining 3, 250-300 μg/ day. The T4 dose required to suppress TSH resulted in normal serum concentrations of T₄) 9.1 ± 2.0 μg/dl, and T₃, 136.7 ± 33.6 ng/dl. These T₄ doses did not produce a rapid heart rate, either awake or asleep, arrhythmias, or electrocardiographic abnormalities as assessed by 24-h Holter monitor tracings in 11 patients. Our results thus show that the T₄ dose which results in an unresponsive TRH test ensures that serum TSH will remain undetectable (<0.6 μ, U/ml) throughout the 24-h period. An unresponsive TRH test, therefore, appears to be a very useful and reliable index of TSH suppression.