Usefulness of different biochemical markers of the insulin-like growth factor (IGF) family in diagnosing growth hormone excess and deficiency in adults

The diagnostic approach to acromegaly and GH deficiency frequently includes measurement of several components of the insulinlike growth factor (IGF) s ystem. 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-bindin g protein-3 (IGFBP-3), acid-labile subunit (ALS), and free IGF-I reflect th e GH secretory status, but their diagnostic accuracy is still debated. In t his study serum levels of total and free IGF-I, IGFBP-3, ALS, and IGFBP-3-I GF-I and IGFBP-3-ALS complexes were determined in patients previously diagn osed 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 declin ed 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 so 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 correlat ion 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 a ctive acromegalic patients, all parameters had only a modest sensitivity in GHD; suppression below -2 Sn was observed in 41% of GHD patients for IGF-I , 47% for IGFBP-3, 32% for ALS, and 35% for free IGF-I measurements. Previo us radiotherapy and GH peak response below 3 mug/L were associated with sig nificantly lower IGF-I, IGFBP-3, and ALS levels. IGF-I levels were signific antly correlated to ALS (r = 0.68; P < 0.001) and IGFBP-3 (r = 0.64; P <les s than> 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 imp aired was the most predictive indicator of IGF-I, IGFBP-3, and free IGF-I l evels 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 l evels were elevated in 15% of cases: On the other hand, both IGFBP-3 comple xes were able to predict GHD; in only a minority of cases. Taken together, these data support the diagnostic role of IGF-I in acromega ly and suggest that free IGF-I and the IGFBP-3-IGF-I complex can assist dia gnostic strategies in this condition. All markers are of limited predictive value in adult GHD, as hormonal values are commonly found within the norma l limits. In these patients, low IGFBP-3 and IGF-I concentrations can add f urther clinical information on the residual GH activity.