ACIPIMOX POTENTIATES GROWTH-HORMONE RESPONSE TO GROWTH HORMONE-RELEASING HORMONE BY DECREASING SERUM-FREE FATTY-ACID LEVELS IN HYPERTHYROIDISM

Hyperthyroidism is associated with an impairment of growth hormone (GH ) responses to secretagogues. The aim of this study was to evaluate th e effect of acipimox, an antilipolytic agent able to decrease free fat ty acids (FFA), on GH response to OH-releasing hormone (GHRH) in hyper thyroid and normal control subjects. We studied six men with hyperthyr oidism; seven normal men served as control subjects. Each subject unde rwent treatment with (1) 2 tablets of placebo orally or (2) 500 mg aci pimox orally, 120 minutes before intravenous (IV) injection of 1 mu g/ kg GHRH-(1-29)WH2. GH response to GHRH in hyperthyroid patients was ma rkedly reduced; the mean peak GH response (9.6 +/- 1.0 mu g/L) and the area under the GH response curve (12.9 +/- 1.3 mu g/L x 2 h) were low er than those of control subjects (25.7 +/- 1.8 mu g/L, P <.05; 28.7 /- 2.1 mu g/L x 2 h, P <.05). Hyperthyroid patients had higher baselin e levels of plasma FFA than control subjects (998.0 +/- 38.9 v 498.0 /- 36.0 mu Eq/L, P<.01). Acipimox decreased FFA levels in both hyperth yroid and control subjects; the lowest FFA levels of hyperthyroid subj ects induced by acipimox were similar to those of control subjects. Af ter acipimox pretreatment, GH responses to GHRH increased significantl y (P <.05); the mean peak plasma GH level (25.9 +/- 4.6 mu g/L) was si milar to the peak GH levels of control subjects during the GHRH test, and the area under the GH response curve (41.1 +/- 6.7 mu g/L x 2 h) w as even higher than that of control subjects with the GHRH test. Howev er, the enhanced GH responses of hyperthyroid patients were still lowe r that those of control subjects during the acipimox plus GHRH test. W e demonstrated that the decreased FFA levels induced by acipimox poten tiate somatotrope responsiveness, likely acting at the pituitary level . Our results indicate that high FFA levels are responsible for impair ed GH responses to GHRH in hyperthyroidism. Copyright (C) 1995 by W.B. Saunders Company