Cancer in GH excess and GH deficit.

The relationship between GH excess and cancer is a controversial matter. Until 2016, most studies in patients with acromegaly found links with colon and thyroid neoplasms. However, recent studies found increased cancer risks in gastric, breast, and urinary tract cancer also. Concordantly, clinical situations where GH and IGF-I deficit exist, are indeed associated with diminished malignancy incidence. In line with these observations, gain-of-function mutations of various enzymes belonging to the GH and IGF-I signaling pathways have been associated to increased carcinogenesis; similarly, loss-of-function mutations of other enzymes that usually work as tumor repressors are also associated to augmented cancer risk. In a study performed in Ecuador it was demonstrated that subjects in the Ecuadorian cohort with Laron syndrome (ELS), who have a mutant GH receptor and greatly diminished GH and IGF-I signaling, display diminished incidence of cancer. Along with absent action of GH and IGF-I, ELS individuals also have low serum insulin levels and decreased insulin resistance. Furthermore, hyperglycemia and hyperinsulinemia are indispensable for fast cell mitosis, including that of those cells present in benign and malignant neoplasms. Notably, and despite their obesity, subjects in the ELS display normoglycemia and hypo-insulinemia, along with diminished incidence of malignancies. We believe that the dual low-IGF-I/low insulin serum levels is responsible for the cancer protection, especially considering that the insulin/INSR signaling is a central site for energy generation in the form of ATP and GDP, which are indispensable for all and every GH/IGF-I physiologic as well as pathologic events.