EFFECTS OF SYNTHETIC PYROGLUTAMYL-HISTIDYL-PROLINE-AMIDE ON SERUM LEVELS OF THYROTROPHIN, CORTISOL, GROWTH HORMONE, INSULIN AND PBI IN NORMAL SUBJECTS AND PATIENTS WITH PITUITARY AND THYROID DISORDERS

Abstract

Effects of single rapid iv injections of synthetic pyroglutamyl-histidyl-proline amide (TRH) in doses of 100 and 200 μg in nine normal subjects and patients with pituitary and thyroid disorders were evaluated by clinical observation and serial measurements of serum levels of human thyrotrophin (HTSH), cortisol, growth hormone (STH), insulin and PBI. An onset of fatigue was observed in about half of the patients six to eight hours after the injection of TRH and lasted several hours. A rise in serum HTSH was detectable within 10 min after the administration of 100 μg of TRH in all normal subjects, reaching a maximum in 15 min in seven of these nine individuals and at 30 and 120 min in two subjects; and then gradually decreased over the next two hours, when the mean level was still above the baseline. Three of nine time courses of serum HTSH showed two peaks, a first at 5 to 15 min and a second at 30 to 120 min. Increases in serum PBI were measurable within 120 min after TRH. Multiple effects of TRH on HTSH, cortisol and STH levels in serum were found in six of nine normal subjects. The percentage increases were frequently larger for STH than for HTSH levels and the effect was heterogeneous on the time courses of these two hormones. An increase in serum HTSH occurred in four untreated patients with acromegaly, and a slow and prolonged response in two of three patients with primary hypothyroidism after 200 μg of TRH. One woman with Sheehan's syndrome showed no rise in serum HTSH at 100 μg of TRH but a moderate rise at 200 μg of TRH. Another patient with an operated chromophobe adenoma and panhypopituitarism responded normally to 100 μg of TRH. Clinical studies involving the use of various synthetic derivatives of TRH are needed to evaluate the clinical response of the tripeptide.