The ratio between serum levels of insulin‐like growth factor (IGF)‐I and the IGF binding proteins (IGFBP‐1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients

OBJECTIVE: Several in-vitro studies have suggested that the biological actions of IGF-I can be modified by the presence of specific IGF binding proteins. In man, the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term changes in the IGF-I/IGFBP-3 ratio have been described following GH administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated in active acromegaly due to excessive GH secretion. However, the individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously. METHODS AND MATERIALS: We studied this ratio in 198 healthy adults and in 56 acromegalic patients, grouped according to their serum GH levels (group I GH 10 mIU/l). In all subjects a single blood sample was drawn for IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and GH measurements by specific RIAs. In 38 of the patients a 24-hour urinary collection was performed for GH determination. RESULTS: In healthy adults serum levels of IGF-I and IGFBP-3 decreased with increasing age (r = -0.52 and r = -0.34, respectively, P < 0.0001). In addition, the molar IGF-I/IGFBP-3 ratio declined with increasing age (r = -0.44, P = 0.0001). In patients with acromegaly and high serum GH levels (group III), circulating IGF-I was increased 7.97 standard deviations (SDS) and IGFBP-3 was increased 4.20 SDS (P < 0.0001). Serum levels of IGF-II were normal in all three groups (588 +/- 240 micrograms/l) whereas IGFBP-1 and IGFBP-2 levels were low and IGFBP-2 levels decreased significantly with increasing serum GH levels (P < 0.0001). The molar IGF-I/IGFBP-3 ratio in the acromegalic patients was significantly higher than in the controls (P < 0.0001) and correlated significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with serum GH levels (r = 0.73, P < 0.0001). CONCLUSION: We demonstrated a decreasing molar IGF-I/IGFBP-3 ratio with increasing age in healthy adults and an increased ratio between serum IGF-I and IGFBP-3 levels in acromegalic patients. As IGF-II is normal and IGFBP-1 and IGFBP-2 are inversely correlated to the serum GH levels in the acromegalic patients, we speculate that the molar ratio between IGF-I and IGFBP-3 reflects free (biologically active) IGF-I and is dependent on GH levels.