BIOACTIVITY OF THYROTROPIN (TSH) IN PATIENTS WITH CENTRAL HYPOTHYROIDISM - COMPARISON BETWEEN IN-VIVO 3,5,3'-TRIIODOTHYRONINE RESPONSE TO TSH AND IN-VITRO BIOACTIVITY OF TSH

To investigate the cause(s) of central hypothyroidism with normal or e levated TSH concentrations, we evaluated the bioactivity of serum TSH as well as pituitary and thyroid function. Seven hypothyroid patients had documented deficiencies of anterior pituitary hormones other than TSH. Basal TSH concentrations ranged from 2.2-14.8 mu U/mL. Six patien ts had low T-4 and free T-4 concentrations; the remaining patient had a low free T-4 and a low normal T-4 level with an elevated TSH concent ration of 14.4 mu U/mL. The mean increment in TSH 30, 60, and 90 min a fter TRH administration (mean Delta TSH) in these patients was 13.5 +/ - 9.1 mu U/mL (mean +/- SD), which was not significantly different fro m the value in controls (9.2 +/- 3.5 mu U/mL). However, the ratio of t he T-3 increment at 120 min (Delta T-3) to mean Delta TSH (Delta T-3/m ean Delta TSH) in patients was 53.9 +/- 29.3 ng/mu U, significantly lo wer than the control value of 239.5 +/- 97.5 ng/mu U (P < 0.01), sugge sting that the thyroid response to endogenous TSH was blunted. The ser um T-4 concentration correlated with the mean Delta TSH in these patie nts (r = 0.78; P < 0.05), suggesting that hypothyroidism is dependent on conserved pituitary function. The mean bioactivity to immunoreactiv ity ratio of basal TSH in patients was 0.97 +/- 0.27 and was not signi ficantly different from the normal value of 1.05 +/- 0.22. One of the two patients with high basal TSH (>10 mu U/mL) had a ratio of 0.59, wh ich is just below the mean +/- SD of normal subjects (0.61), suggestin g that most patients had normal TSH bioactivity in vitro. Our findings suggest that in vivo bioactivity of TSH is decreased because of a pit uitary disorder, but in vitro bioactivity of TSH is variable in patien ts with central hypothyroidism.