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These studies were undertaken to clarify the physiological role of thyrotropin releasing hormone (TRH) in regulation of the hypothalamic pituitary thyroid axis. Synthetic TRH was administered both acutely as a single intravenous dose of 500 micrograms (TRH IV) and chronically (TRH p.o.), in the form of repetitive oral doses (10 mg b.i.d. for 4 days) to 21 normal, 26 hypothyroid, and 14 hyperthyroid subjects. Serial determinations were made of the serum levels of thyrotropin (TSH), triiodothyronine (T3) and thyroxine (T4) after TRH IV nd TRH p.o. and changes in thyroidal untake of redioiodine thyroxine were assessed after TRH p.o. In normal subjects, serum TSH and T3 rose in response to TRH IV but there was no significant change in the serum T4 levels. The peak levels of serum TSH (TSH PL) ranged from 7.0 to 30.0 microunits per ml and serum T3 levels (T3 PL) from 126.2 to 197.4 ng/dl. After the first TRH p.o. dose, serum TSH levels rose (TSH PL: 7.0 approximately 34.0 microunits per ml) but the TSH increment decreased in response to subsequent doses of TRH . Nevertheless, both the mean serum T3 and T4 levels increased progressively in response to TRH p.o. reaching their peak levels on the 4th day (Mean T3 PL: 185.1 +/- 4.0 ng/dl with a range of 152.8 to 216.8; Mean T4 PL:11.7 +/- 0.8 micrograms/dl with a range of 8.4 to 13.4). The mean 24-hour131I uptake also increased by 19.9 +/- 1.2% D over baseline with a range 9.1 to 30.7. After intramuscular TSH, the mean increment in a 24-hour 131I uptake was 13.2 +/- 1.0% D with a range of 5.6 to 20.8%. In all 26 patients with hypothyroidism, serum T3 and T4 failed to increase in response to TRH IV. Based on the TSH PL after TRH IV and the criteria of Pittman, the patients could be provisionally divided into primary hypothyroidism (13 patients whose TSH PL ranged from 52.5 to 500 microunits per ml), secondary or pituitary hypothyroidism (8 patients whose TSH PL varied from undetectable to 4.1 microuints/ml) and tertiary or hypothalamic hypothyroidism (5 patients whose TSH PL was from 8.8 to 30.4 microunits/ml)...

The Hypothalamic-Pituitary Thyroid Axis : Studies on the Regulatory Role of Thyrotropin Releasing Hormone (TRH)