INFLUENCE OF HYPERTHYROIDISM ON GROWTH-HORMONE SECRETION

OBJECTIVE Hyperthyroidism is associated with altered GH secretion. Whe ther this is due to changes of somatotroph responsiveness or reflects an alteration in negative feedback signals at the hypothalamic level i s unknown. We therefore performed a series of studies to shed some lig ht onto this issue. DESIGN Study 1: GHRH (1 mug/kg b.w.) was injected i.v. in 38 hyperthyroid patients and in 30 normal subjects; in 11 of t he patients the GHRH test was repeated following methimazole-induced r emission of hyperthyroidism. Study 2: hGH (2 U i.v.) or saline were ad ministered 3 hours prior to GHRH; six hyperthyroid patients and six no rmal subjects were studied. Study 3: ten normal subjects and ten hyper thyroid patients were given 75 g oral glucose or water 30 minutes befo re GHRH. Study 4: 11 normal subjects and eight hyperthyroid patients w ere studied. TRH or vehicle were dissolved in 250 ml of saline solutio n and infused at a rate of 400 mug/h for 150 minutes. Thirty minutes a fter the beginning of the infusions, L-arginine (30 g infused over 45 min i.v.) was administered. PATIENTS Hyperthyroid patients were compar ed to normal subjects. MEASUREMENTS Growth hormone was measured by RIA at 15-minute intervals. RESULTS GH responses to GHRH were subnormal i n hyperthyroid patients. Following antithyroid drug treatment with met himazole, GH responses to GHRH increased in these patients in comparis on to pretreatment values. Serum IGF-I levels, which were elevated bef ore treatment, decreased after methimazole administration. Exogenous G H administration induced a clear decrease of GH responses to GHRH in b oth control and hyperthyroid subjects. On the other hand, oral glucose load decreased the GH responses to GHRH in normal but not in hyperthy roid subjects. TRH administration did not modify the GH responses to a rginine in either normal subjects or hyperthyroid patients. CONCLUSION S Hyperthyroidism is associated with increased serum IGF-I levels and marked alterations in the neuroregulation of GH secretion. These chang es involve decreased GH responsiveness to GHRH at the pituitary level and, at the hypothalamic level, a lack of suppressive effect of an ora l glucose load. The normal inhibitory effect of exogenous GH administr ation but not of an oral glucose load in hyperthyroid patients suggest s that these two feedback signals act through different mechanisms. Th e lack of effect of a TRH infusion on GH responses to L-arginine in no rmal and hyperthyroid patients makes an inhibitory role for TRH in GH secretion unlikely, at least in Caucasian subjects.