The insulin-like growth factor-I generation test: peripheral responsiveness to growth hormone is not decreased with ageing

OBJECTIVE: Ageing is accompanied by a reduction in GH secretion, and a decrease in circulating IGF-I. Few data are available on whether the responsiveness of IGF-I to GH stimulation changes with age. SUBJECTS AND METHODS: Therefore we carried out multiple IGF-I generation tests in 26 healthy volunteers (16 male) of normal body mass index (BMI); nine aged 20-40 years, six aged 41-60 years, and 11 aged > 61 years. Each subject received three single doses of GH: 0.8, 2.0 and 21 IU in random order at least 4 weeks apart. Serum samples were taken 0, 18, 24, 48, 72 and 120 h following each dose of GH. RESULTS: Basal serum levels of IGF-I (P < 0.0001) and IGFBP-3 (P < 0.01) declined with age, but serum acid-labile subunit (ALS) levels did not (P = 0.2). Peak IGF-I levels (P < 0.01 for 0.8 IU and P < 0.05 for the 2 IU dose) and area under curve (AUC) IGF-I (P < 0.01 for the 0.8 IU and 2.0 IU doses of GH and P < 0.05 for the 21 IU dose) after GH administration continued to demonstrate a significant trend towards lower values with increasing age. However, the increment in IGF-I, IGFBP-3 and ALS in response to GH did not decline with age. Indeed, the increment in IGF-I after 2 IU of GH, judged by the increase from basal to peak levels, increased with advancing age (P = 0.05), and a positive relationship was seen between the increment in the area under the IGF-I curve following the 21 IU dose of GH and age (P < 0.02). CONCLUSION: These data illustrate that although activity of the GH/IGF-I axis declines with age, peripheral responsiveness to GH is not attenuated. This suggests that a decrease in GH responsiveness does not contribute to the age-related fall in circulating GH-dependent peptides. Thus, for those embarking on trials of GH therapy or GH secretagogues in the elderly, the capacity to generate IGF-I will not limit potential efficacy. Furthermore, the dose of GH replacement required for patients with organic GH deficiency is likely to be lower in the elderly compared with young adults.