Consistent with this, chronic sustained hyperinsulinemia can amplify the growth-promoting effects of insulin in patients with severe monogenic IR syndromes, most often due to mutation of the INSR gene, in which acanthosis nigricans, organomegaly, pseudo-acromegaloid soft tissue overgrowth, ovarian tumors, and colonic polyposis are the direct consequence of excessive circulating insulin [51,52,53]. This evidence concerns the gene INSR and hyperinsulinism.