Response to Thyrotropin Releasing Hormone: An Objective Criterion for the Adequacy of Thyrotropin Suppression Therapy

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Abstract
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 after 131I 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 (4) at doses which resulted in undetectable TSH values in random plasma samples. TRH tests were carried out only when random TSH concentrations were 4 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 /xg 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 /μU/ml) throughout the 24-h period. An unresponsive TRH test, therefore, appears to be a very useful and reliable index of TSH suppression.

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