INS and Cushing syndrome due to macronodular adrenal hyperplasia: In subjects with Cushing syndrome as the endogenous hypercortisolemia exacerbates, the relative insulinopenia becomes more paramount, suggesting that relative insulinopenia is caused by cortisol-mediated direct or indirect “toxic” effects on the pancreatic β-cells, which suppresses endogenous insulin secretion [21,22].