COMBINED PYRIDOSTIGMINE THYROTROPIN-RELEASING-HORMONE TEST FOR THE EVALUATION OF HYPOTHALAMIC SOMATOSTATINERGIC ACTIVITY IN HEALTHY NORMAL MEN

Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear grow th hormone (GH) release in man by suppression of hypothalamic somatost atin (SRIH). Somatostatin suppresses thyrotrophin (TSH) release in rat s and men. Earlier studies showed that the thryotrophin-releasing horm one (TRH)-induced TSH response was not altered by 60-120 mg of PST. We studied whether a larger dose (180 mg) of PST can increase the TSH re sponse to TRH. Six healthy young men were studied with the following s ix tests: (Test 1) 200 mu g of TRH iv; (Test 2) 180 mg of PST po; (Tes t 3) three different doses of PST (60, 120, 180 mg)+ TRH; (Test 4) 100 mu g of octreotide (SMS) iv; (Test 5) SMS + TRH; (Test 6) PST + SMS TRH. A large dose of PST (180 mg) significantly augmented GH, TSH and prolactin responses to TRH, while smaller doses of PST (60 and 120 mg ) did not significantly increase the responses of GH and TSK. While th e increased TRH-induced prolactin response by PST was not suppressed b y SMS, the increased responses of GH and TSH were suppressed remarkabl y by SMS. Most of the subjects noticed a mild to moderate abdominal pa in, nausea and muscular fasciculation after the administration of a la rge dose of PST administration. These data suggest that suppression of hypothalamic SRIH secretion by 180 mg of PST can augment the TSH resp onse to TRH. However, the considerable side effects should be minimize d before clinical application of the combined PST-TRH test.