Multiphasic thyrotropin responses to thyroid hormone administration in man.

The magnitude and temporal pattern of serum TSH suppression after single or multiple doses of thyroid hormone (T3, T4, or triiodothyroacetic acid) were studied using third and fourth generation TSH assays (sensitivities, 0.01 and 0.001 mU/L, respectively). A constant T3 dose (263 micrograms i.v.) administered at a uniform clock time (1200 h) produced identical serum TSH suppression patterns, (percent of control TSH vs. hours) in euthyroid and hypothyroid subjects. The percent log TSH vs. log time plot revealed three temporally distinct linear suppression phases: phase 1, a rapid TSH suppression, onset 1 h and lasting for 10-20 h; phase 2, slower suppression, onset between 10 and 20 h and lasting for 6-8 weeks; and phase 3, an invariable low TSH level (< 0.01 mU/L) with chronic T3 suppression (100 micrograms four times a day). TSH escaped maximal suppression at a similar serum T3 level in both euthyroid and hypothyroid subjects (2.9 +/- 0.2 vs. 3.5 +/- 0.5 nmol/L, respectively; P > 0.9), despite different basal serum T3 values (2.0 +/- 0.1 vs. 0.6 +/- 0.1 nmol/L, respectively; P < 0.01). Two milligrams of triiodothyroacetic acid or 2 mg T4 given iv at 1200 h produced TSH suppression patterns similar to T3. The phase 1 suppression varied with the clock time of T3 administration, (steeper responses were seen at 2400 vs. 1200 h), whereas phase 2 responses were unaltered. This study shows that thyroid hormone suppression of TSH is a complex, biphasic, nonlinear process, which is reproducible and independent of thyroid status or the thyroid hormone analog used. It is hypothesized that phase 1 reflects inhibition of release of preformed hormone, whereas phase 2 likely reflects inhibition of de novo synthesis and/or thyrotroph storage of TSH. In contrast, phase 3 secretion seems to represent basal constitutive TSH release, which may have relevance to the role of thyroid hormone-suppressive therapy in the treatment of patients with benign or neoplastic thyroid disease.

Thyrotropin (TSH)-releasing hormone stimulation test responses employing third and fourth generation TSH assays.

TRH stimulation tests (n = 1109) were performed on 1061 ambulatory and 43 hospitalized patients with varying thyroid status, using a TSH immunochemiluminometric assay with third and fourth generation sensitivity characteristics (functional sensitivity, 0.01 and 0.001 mU/L, respectively). TRH test results were analyzed as both absolute (stimulated minus basal TSH) and fold (stimulated/basal TSH) responses. The absolute TRH response varied 8-fold across the physiological TSH range, whereas the mean fold response remained almost constant (mean +/- SEM, 8.5 +/- 0.2). The fold response became progressively attenuated as basal TSH values declined below physiological levels, becoming essentially absent in clinically thyrotoxic patients with markedly depressed basal serum TSH levels (0.007 +/- 0.002 mU/L). Progressive attenuation also occurred at hypothyroid TSH levels; a markedly impaired fold response (2.5 +/- 0.4) was characteristic of primary hypothyroid patients with basal TSH values greater than 50 mU/L. In untreated central hypothyroid patients with near-normal basal TSH levels, the TRH fold response was impaired (1.7 +/- 0.2), whereas in T4-replaced central hypothyroid patients, fold responses were near normal (5.6 +/- 1.2). Neither nonthyroidal illness, age, or sex appeared to influence the pattern of fold TRH response in the populations evaluated. When using third and fourth generation TSH methodology, the TRH-stimulated TSH fold response is more diagnostically useful than the absolute TRH response. However, if patients have an intact hypothalamic-pituitary axis, there appears to be no diagnostic advantage gained by TRH testing over an accurately measured basal TSH value.