Effect of prolonged oral administration of TRH on plasma levels of thyrotrophin and prolactin in normal individuals and in patients with primary hypothyroidism.

Forty mg TRH/day was given orally for 3 weeks to 10 euthyroid women and 10 women with primary hypothyroidism on low replacement doses of thyroxine. Once weekly oral TRH was replaced by an iv TRH-test (0.4 mg) with measurement of serum concentration of TSH, prolactin (PRL), thyroxine (T4), triiodothyronine (T3) and cholesterol. In the normal group, mean serum T4 concentration increased after one week and remained elevated. Serum TSH concentration showed a slight tendency to decline. Maximal rise in TSH concentration after iv TRH (deltaTSH) fell from a mean of 4.0 ng/ml to 1.4 ng/ml within one week and stayed low. T3, cholesterol, PRL and deltaprl were normal and unchanged throughout. In the hypothyroid group T4, T3, cholesterol, PRL and deltaPRL were not influenced by the TRH administration. In 2 patients (with the highest serum T4 concentrations) serum TSH concentration was normal and resistant to iv TRH. Of the 8 patients with elevated TSH, basal level and deltaTSH did not change in 2 (with subnormal T4 levels and the highest TSH levels). In the other 6 (with intermediate T4 levels) basal TSH fell from a mean of 10.1 ng/ml to 4.2 ng/ml, and deltaTSH from 10.0 ng/ml to 3.3 ng/ml after three weeks. It is concluded that in addition to feed-back effect of thyroid hormones, the pituitary response to long-term administration of TRH is determined by other factors. Among these may be reduced pituitary TRH receptor capacity and the activity of the TSH producing cells.