Challenges and controversies in the surgical management of uremic hyperparathyroidism: A systematic review.

BACKGROUND: Prevalence of uremic hyperparathyroidism (uHPT), secondary and tertiary, continues to rise. Historically, surgery was the only durable treatment for these conditions, but with the development of pharmacologic options, the treatment landscape has shifted predominantly towards medical management. Presently, there is a paucity of clear guidelines for surgical indications in the treatment of uHPT. In this review, we will discuss the risks and benefits associated with surgical management of uHPT and will evaluate recent evidence and controversies surrounding indications for parathyroidectomy (PTX) in uHPT. DATA SOURCES: A systematic review of the literature was performed, in accordance with PRISMA guidelines, resulting in the evaluation of 69 articles. CONCLUSIONS: Significant controversy still exists regarding indications and timing of surgical management of uHPT. Although the benefits of PTX in the uHPT patient population have been established, there is a significant need for well-designed randomized clinical trials to further clarify existing guidelines and optimize treatment approaches.

Effects of oxidative stress on intestinal type I insulin-like growth factor receptor expression.

INTRODUCTION: Oxidative stress activates multiple signaling transduction pathways, including the phosphatidylinositol 3-kinase (PI3-K), in an injured intestine as occurs in necrotizing enterocolitis (NEC). We have previously shown that hydrogen peroxide (H2O2)-induced PI3-K activation is significantly enhanced with exogenous insulin-like growth factor (IGF)-1 in intestinal epithelial cells. However, the effects of oxidative stress on IGF receptor type I (IGF-IR) activation and expression in the neonatal intestine during NEC are unknown. MATERIAL AND METHODS: Intestinal sections from neonates undergoing bowel resections (control = 3, NEC = 20) were analyzed for IGF-IR expression. NEC was induced in newborn mouse pups using hypoxia and hyperosmolar feeds, and distal small bowel segments were analyzed for IGF-IR expression (control = 3, NEC = 7). H2O2 was used to induce oxidative stress in rat (RIE-1) and fetal human (FHs74 Int) intestinal epithelial cells. Phosphorylation of IGF-IR, Akt, a downstream effector of PI3-K, and IGF-IR levels were determined by Western blotting. Flow cytometry, immunofluorescence, immunohistochemistry, IGF-IR tyrosine phosphorylation array, cell death enzyme-linked immunosorbent assay, and Western blotting were used to determine the IGF-IR expression. RESULTS: An increased IGF-IR expression was noted in intestinal sections from NEC as well as murine model of NEC. H2O2 treatment rapidly activated IGF-IR and increased the expression in RIE-1 and FHs74 Int cells. Inhibition of IGF-IR resulted in significant RIE-1 cell apoptosis during oxidative stress. IGF-IR tyrosine phosphorylation array showed the recruitment of several key SH2 domain-containing proteins and oncogenes to the IGF-IR tyrosine kinase domain in H2O2-treated RIE-1 cells. CONCLUSION: IGF-IR-mediated activation of intracellular signaling may play a critical role during oxidative stress-induced apoptosis in NEC.