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.


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).


CONCLUSIONS
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.
Lissett
Catherine A
CA
Department of Endocrinology, Christie Hospital, Manchester, UK.
Shalet
Stephen M
SM
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D019540:Area Under Curve; D015992:Body Mass Index; D005260:Female; D013006:Growth Hormone; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D018709:Statistics, Nonparametric
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone