Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: Since the release of the 2022 Second International Workshop Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines, updates and advances are now available in the cause, complications, and treatment of adult chronic hypoparathyroidism (hypoPTH). This review aims to highlight these new findings and implications to patient care.

Recent findings: Postsurgical hypoparathyroidism remains the most common cause, immune-related hypoparathyroidism from checkpoint inhibitors is an emerging autoimmune cause. In a large retrospective cohort study of thyroidectomies, incident fracture was lower, particularly in the vertebra, in the hypoPTH cohort, compared with postthyroidectomy control group. Hypercalciuria increases risk for renal calculi in hypoPTH independent of disease duration and treatment dose. Quality of life is impaired in hypoPTH patients on conventional therapy, improvement was noted post-PTH replacement. TranCon PTH phase 3 RCT reported eucalcemia with reduced renal calcium excretion, normalization of bone turn-over markers, stable BMD and improved quality of life.

Summary: HypoPTH is a chronic disease associated with significant morbidity and poor Quality of Life. Awareness of treatment targets and follow-up investigations can alleviate patient anxiety regarding over-treatment and under-treatment. Progress in long-acting PTH replacement strategies might provide accessible, feasible alternatives to conventional therapy in brittle hypoPTH patients.

Purpose of review: Disturbances in mineral and bone metabolism occurring in osteoporosis and chronic kidney disease-associated osteoporosis place patients at high risk of fracture making these conditions a major public health concern. Due to the limited use of bone histomorphometry in clinical practice, the gold standard for assessing bone turnover, extensive efforts have been made to identify bone turnover markers (BTMs) as noninvasive surrogates. Since the identification of certain commonly used markers several decades ago, considerable experience has been acquired regarding their clinical utility in such bone disorders.

Recent findings: Mounting evidence suggested that BTMs represent a simple, low-risk, rapid and convenient way to obtain data on the skeletal health and that they may be useful in guiding therapeutic choices and monitoring the response to treatment.

Summary: BTMs could provide clinicians with useful information, independent from, and often complementary to bone mineral density (BMD) measurements. They have proven valuable for monitoring the effectiveness of osteoporosis therapy, as well as promising for discriminating low and high turnover states. Improved performance is observed when BTMs are combined, which may be useful for selecting treatments for chronic kidney disease-bone mineral disorders (CKD-MBD).

Purpose of review: Fibroblast growth factor 23 (FGF23) is a hormone to reduce blood phosphate concentration. Excessive actions of FGF23 induce FGF23-related hypophosphatemic disorders, such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). We will summarize recent advances in the diagnosis and treatment of FGF23-related hypophosphatemic disorders.

Recent findings: The measurement of blood FGF23 is useful to make a diagnosis of FGF23-related hypophosphatemic disorders. It was reported that many patients with FGF23-related hypophosphatemic disorders, especially TIO, were misdiagnosed, therefore, it is necessary to enhance the awareness of these diseases. A novel method to inhibit excessive actions of FGF23 by a human monoclonal antibody for FGF23, burosumab, has been approved in several countries. In more long-term observation than clinical trials, burosumab has also been shown to improve biochemical abnormalities and symptoms of rickets/osteomalacia. Following these advances, several registries and consensus recommendations on FGF23-related hypophosphatemic disorders, especially XLH, have been established in each country or region.

Summary: Further long-term effects of burosumab and the precise mechanism of FGF23 overproduction in patients with FGF23-related hypophosphatemic disorders need to be clarified in the future studies.

Purpose of review: Potassium-competitive acid blockers (PCABs) represent a new class of compounds for the treatment of acid-related disorders. Recent FDA approval of the PCAB vonoprazan for erosive esophagitis has started an important new approach to acid-related disorders.

Recent findings: Compared to conventional proton pump inhibitors (PPIs), PCABs provide more rapid, potent, and sustained suppression of gastric acid with faster and more durable symptom relief. Studies have demonstrated the efficacy of PCABs for erosive esophagitis, nonerosive reflux disease, and peptic ulcer disease including H. pylori. However, the PCAB vonoprazan was only approved in the US as part of combination therapy for eradication of H. pylori. Clinical trials have now demonstrated noninferiority of vonoprazan to lansoprazole for treatment of erosive esophagitis, particularly noting superiority of vonoprazan in patients with severe esophagitis resulting in FDA approval of vonoprazan for treatment of erosive esophagitis. Emerging data suggests a possible utility of vonoprazan for PPI-resistant gastroesophageal reflux disease (GERD) and on-demand therapy for nonerosive reflux disease. Vonoprazan is generally well tolerated but long-term safety data is not well established.

Summary: The PCAB vonoprazan is a newly FDA approved treatment option for erosive esophagitis. Its possible role in PPI-resistant GERD and nonerosive reflux disease warrants further investigation.

Purpose of review: Metabolic and bariatric surgery (MBS) and endoscopic bariatric therapies (EBT) are being increasingly utilized for the management of obesity. They work through multiple mechanisms, including restriction, malabsorption, and changes in the gastrointestinal hormonal and motility.

Recent findings: Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) cause decrease in leptin, increase in GLP-1 and PYY, and variable changes in ghrelin (generally thought to decrease). RYGB and LSG lead to rapid gastric emptying, increase in small bowel motility, and possible decrease in colonic motility. Endoscopic sleeve gastroplasty (ESG) causes decrease in leptin and increase in GLP-1, ghrelin, and PYY; and delayed gastric motility.

Summary: Understanding mechanisms of action for MBS and EBT is critical for optimal care of patients and will help in further refinement of these interventions.

Purpose of review: Various gut hormones interact with the brain through delicate communication, thereby influencing appetite and subsequent changes in body weight. This review summarizes the effects of gut hormones on appetite, with a focus on recent research.

Recent findings: Ghrelin is known as an orexigenic hormone, whereas glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), postprandial peptide YY (PYY), and oxyntomodulin (OXM) are known as anorexigenic hormones. Recent human studies have revealed that gut hormones act differently in various systems, including adipose tissue, beyond appetite and energy intake, and even involve in high-order thinking. Environmental factors including meal schedule, food contents and quality, type of exercise, and sleep deprivation also play a role in the influence of gut hormone on appetite, weight change, and obesity. Recently published studies have shown that retatrutide, a triple-agonist of GLP-1, GIP, and glucagon receptor, and orforglipron, a GLP-1 receptor partial agonist, are effective in weight loss and improving various metabolic parameters associated with obesity.

Summary: Various gut hormones influence appetite, and several drugs targeting these receptors have been reported to exert positive effects on weight loss in humans. Given that diverse dietary and environmental factors affect the actions of gut hormones and appetite, there is a need for integrated and largescale long-term studies in this field.