INSULIN-LIKE GROWTH-FACTOR (IGF)-I AND (IGF)-II AND IGF BINDING-PROTEIN (IGFBP)-1, (IGFBP)-2 AND (IGFBP)-3 IN SERUM FROM PATIENTS WITH CUSHINGS-SYNDROME

In the present study of twenty-two patients with Cushing's syndrome, s erum insulin-like growth factor (IGF)-I concentrations were normal to high with an increased mean IGF-I concentration, 40% above that of hea lthy subjects of the same age (p<0.001). Serum IGF-II concentrations w ere normal. The morning serum IGF binding protein (IGFBP)-I concentrat ions were within the range of healthy controls. IGFBP-1 was inversely correlated to the IGF-I concentration (p<0.001) and to the 24 h urinar y cortisol excretion (p<0.005) with a combined R squared value of 0.58 . In contrast to IGFBP-1, serum IGFBP-2 and IGFBP-3 concentrations wer e elevated by 1.89 +/- 1.78 SD and 0.92 +/- 0.78 SD (mean +/- 2 SD), r espectively. Although increased, the serum IGFBP-2 concentration was i nversely correlated to the IGF-I concentration (r = -0.67. p<0.001). I mmunoreactive IGFBP-3 was increased in proportion to IGF-I and the mol ar ratio IGFBP-3!: IGF-I! + IGF-II! was close to unity (1.04 +/- 0. 14), as that of healthy subjects. In serum from patients with Cushing' s syndrome, with increased immunoreactive IGFBP-3, there was a corresp onding increase in intact glycosylated 40-43 kDa IGFBP-3 as determined by Western ligand blotting. Neutral size chromatography of serum from patients with Cushing's syndrome showed that IGF-I and IGFBP-3 immuno reactivity were predominantly found at the elution volume of the terna ry 150 kDa IGF-I/IGFBP-3/acid labile subunit complex and a similar pat tern was displayed by normal serum. We conclude that the catabolism an d impairment of growth in patients with Cushing's syndrome cannot be a ttributed to the suppression of the GH-endocrine IGF-I axis. Furthermo re, our findings suggest that the previously reported increased IGF in hibitory activity, of low molecular weight, in Cushing's serum could n ot be attributed to IGFBP-3, IGFBP-3 fragments or IGFBP-1. The possibl e role of IGFBP-2 or other IGFBPs in blocking the effects of IGFs has to be further evaluated.