The diagnostic approach to
acromegaly and GH deficiency frequently includes measurement of several components of the
insulin-like growth factor (IGF) system.
IGF-I levels are reported to be good predictors of active and cured
acromegaly, but are commonly found within the normal age-adjusted range in adult GH-deficient (GHD) patients. Circulating concentrations of IGF-binding protein-3 (IGFBP-3),
acid-labile subunit (ALS), and free
IGF-I reflect the GH secretory status, but their diagnostic accuracy is still debated. In this study serum levels of total and free
IGF-I,
IGFBP-3, ALS, and IGFBP-3-IGF-I and IGFBP-3-ALS complexes were determined in patients previously diagnosed with active (n = 67) or inactive (n = 16)
acromegaly and adult GHD (n = 34) and compared with results obtained in 58 healthy controls. In healthy subjects,
IGF-I,
IGFBP-3, ALS, and both
IGFBP-3 complexes declined with age; a correlation was found between
IGF-I and
IGFBP-3 (r = 0.59; P < 0.001), ALS (r = 0.67; P < 0.001), and free
IGF-I (r = 0.40; P < 0.05). Active acromegalic patients showed a significant increase in all parameters tested.
IGF-I concentrations were above +2 SD in 100% of patients, whereas slightly lower sensitivities were shown for
IGFBP-3 (85%), ALS (88%), and free
IGF-I (94%). In this group,
IGF-I exhibited a slightly higher correlation with
IGFBP-3 (r = 0.83; P < 0.001) than with ALS levels (r = 0.78; P < 0.001). In cured acromegalic patients, we observed the normalization of all parameters but free
IGF-I levels. Adult GHD patients showed a significant reduction of all
hormones. Unlike active acromegalic patients, all parameters had only a modest sensitivity in GHD; suppression below -2 SD was observed in 41% of GHD patients for
IGF-I, 47% for
IGFBP-3, 32% for ALS, and 35% for free
IGF-I measurements. Previous
radiotherapy and GH peak response below 3 microg/L were associated with significantly lower
IGF-I,
IGFBP-3, and ALS levels.
IGF-I levels were significantly correlated to ALS (r = 0.68; P < 0.001) and
IGFBP-3 (r = 0.64; P < 0.001) as well as with free
IGF-I (r = 0.67; P < 0.001) levels. By multiple regression analysis, the number of
anterior pituitary hormones impaired was the most predictive
indicator of
IGF-I,
IGFBP-3, and free
IGF-I levels in GHD patients; conversely, the GH peak response better anticipated ALS concentrations. The pattern of
IGFBP-3 complexes paralleled previous hormonal findings. In active acromegalic patients, IGFBP-3-IGF-I levels were 5.4-fold higher than in controls and were above +2 SD in 95% of patients, whereas IGFBP-3-ALS levels were elevated in 15% of cases. On the other hand, both
IGFBP-3 complexes were able to predict GHD in only a minority of cases. Taken together, these data support the diagnostic role of
IGF-I in
acromegaly and suggest that free
IGF-I and the IGFBP-3-IGF-I complex can assist diagnostic strategies in this condition. All markers are of limited predictive value in adult GHD, as hormonal values are commonly found within the normal limits. In these patients, low
IGFBP-3 and
IGF-I concentrations can add further clinical information on the residual GH activity.