High levels of 150-kDa insulin-like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomant-induced serum IGF-I normalization.

Abstract Objective : To assess the effect of pegvisomant-induced serum insulin-like growth factor 1 (IGF-1) normalization on IGF binding proteins 1, 2, 3 (IGFBP-1, IGFBP-2 and IGFBP-3), total, non-bound (45 kDa) and 150-kDa ternary complex-associated IGFBP-3, and in vivo IGFBP-3 proteolysis in patients with active acromegaly. Design : The above parameters were measured in 16 patients (median age 57 (range 27–78)) with active acromegaly (serum IGF-I at least 30% above the upper limit of an age-related reference range after washout) in a paired manner on samples obtained after washout and the first occurrence of serum IGF-I normalization during pegvisomant therapy (median dose 15 mg/day (10–40 mg)). Results : Total IGFBP-3 and 150-kDa ternary complex-associated IGFBP-3 were significantly elevated in patients at baseline compared to controls ((mean ± SEM) 4345 ± 194 vs. 3456 ± 159 μg/L, P P P P P P =0.86; 30 ± 3.5 to 30 ± 3.9%, P =0.75, respectively). Conclusions : GH receptor blockade in patients with acromegaly lowers IGF-I and 150-kDa IGFBP-3 ternary complex formation. 50 kDa ternary complex formation (not in vivo IGFBP-3 proteolysis) is GH dependent and measurement of 150-kDa ternary complex-associated IGFBP-3 may provide useful information regarding treatment efficacy in patients with acromegaly.