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 the effect of acipimox, an antilipolytic agent able to decrease free fatty acids (FFA), on GH response to GH-releasing hormone (GHRH) in hyperthyroid and normal control subjects. We studied six men with hyperthyroidism; seven normal men served as control subjects. Each subject underwent treatment with (1) 2 tablets of placebo orally or (2) 500 mg acipimox orally, 120 minutes before intravenous (IV) injection of 1 μg/kg GHRH-(1-29)NH₂. GH response to GHRH in hyperthyroid patients was markedly reduced; the mean peak GH response (9.6 ± 1.0 μg/L) and the area under the GH response curve (12.9 ± 1.3 μg/L × 2 h) were lower than those of control subjects (25.7 ± 1.8 μg/L, P < .05; 28.7 ± 2.1 μg/L × 2 h, P < .05). Hyperthyroid patients had higher baseline levels of plasma FFA than control subjects (998.0 ± 38.9 v 498.0 ± 36.0 μEq/L, P < .01). Acipimox decreased FFA levels in both hyperthyroid and control subjects; the lowest FFA levels of hyperthyroid subjects induced by acipimox were similar to those of control subjects. After acipimox pretreatment, GH responses to GHRH increased significantly (P < .05); the mean peak plasma GH level (25.9 ± 4.6 μg/L) was similar to the peak GH levels of control subjects during the GHRH test, and the area under the GH response curve (41.1 ± 6.7 μg/L × 2 h) was even higher than that of control subjects with the GHRH test. However, the enhanced GH responses of hyperthyroid patients were still lower that those of control subjects during the acipimox plus GHRH test. We demonstrated that the decreased FFA levels induced by acipimox potentiate somatotrope responsiveness, likely acting at the pituitary level. Our results indicate that high FFA levels are responsible for impaired GH responses to GHRH in hyperthyroidism.