IGFBP1 and Cushing syndrome due to macronodular adrenal hyperplasia: However, when IGFBP-1 levels are chronically lowered during prolonged intra-portal hyperinsulinemia (e.g., obesity, Cushing’s syndrome and glucocorticoid therapy), the “accelerator” effect of IGFBP-1 is at play to increase serum free IGF-I (35, 40).