Acipimox, a nicotinic acid analog, stimulates growth hormone secretion in short healthy prepubertal children

Recent studies in adult volunteers have demonstrated that the free fatty acid reduction induced by acipimox, a nicotinic acid analog, stimulated GH secretion per se and enhanced in an additive manner the GH secretion elicited by such different stimuli as pyridostigmine, GHRH and GHRP-6. In order to evaluate whether acipimox administration stimulates GH secretion in prepubertal children, we administered a single oral dose of acipimox (100 mg for children weighing <30 kg and 200 mg for those >30 kg) to 14 healthy prepubertal children with a mean age of 8.2 +/- 1.9 years, a mean bone age of 6.2 +/- 3.0 years, growing along the 5-10th percentiles, and with normal thyroid function and IGF-I levels. Acipimox administration elicited a sustained increase in GH from a mean baseline level of 0.6 +/- 0.4 to 6.7 +/- 2.4 microg/l at the end of the test (p<0.05), with a mean GH peak of 10.5 +/- 3.5 microg/l. GH release was delayed so that peak GH levels were achieved 180 minutes after acipimox administration. In order to determine whether acipimox was capable of enhancing the GH secretion elicited by levodopa (L-Dopa), we administered either oral L-Dopa (250 mg for children weighing <30 kg and 500 mg for those >30 kg) or oral acipimox plus L-Dopa to the same children on different days. GH concentrations increased in a similar fashion following either of these tests (from a baseline level of 1.2 +/- 0.4 and 0.7 +/- 0.4 microg/l to 8.4 +/- 2.7 and 9.3 +/- 2.9 microg/l at the end of the test (p<0.001), with peak GH concentrations of 13.1 +/- 4.1 and 11.8 +/- 3.3 microg/l after L-Dopa or acipimox plus L-Dopa, respectively). Although the peak GH concentrations obtained after the combined administration of acipimox plus L-Dopa were similar to those obtained after either acipimox or L-Dopa administration, a larger number of our patients reached a GH cut-off point of >7 microg/l following combined therapy than with either stimulus alone (13/14 patients with combined therapy and 10/14 with acipimox alone). No side effects other than mild facial flushing were noted after acipimox administration. These results indicate that: 1) following the administration of a single oral dose of acipimox, significant GH secretion was elicited in healthy short prepubertal children; 2) the combined administration of acipimox plus L-Dopa did not, however, enhance the GH secretion of this group of children; 3) acipimox was well tolerated with minimal side effects; and 4) further studies in both GH sufficient and GH deficient children are necessary to evaluate acipimox's usefulness in assessing GH reserve.