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

D. P. Hoffman, M. I. Surks, J. H. Oppenheimer, E. D. Weitzman

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39 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)892-901
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number5
StatePublished - May 1977

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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