Expert review of endocrinology & metabolism
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Expert Rev Endocrinol Metab · Nov 2020
ReviewTirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes.
The glucagon-like peptide-1 (GLP-1) receptor agonists (RA) have increasingly gained prominence in the treatment of type 2 diabetes (T2D) based on their glycemic benefits and favorable body weight and cardiorenal effects. Despite this, continued development of therapeutics with superior efficacy is important to help address persistent challenges in the attainment of metabolic goals in many patients with T2D. ⋯ Based on data from Phase 2 trials, tirzepatide has the potential to be the most efficacious therapy in T2D with respect to both glucose and body weight control. Data from the ongoing Phase 3 clinical trial program should start to become available in late 2020 and will determine the future course of this promising therapeutic agent.
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Expert Rev Endocrinol Metab · Nov 2019
ReviewHypophysitis induced by immune checkpoint inhibitors: a 10-year assessment.
Introduction: Hypophysitis caused by immune checkpoint inhibitors (ICIs) has risen to the medical attention during the past decade. ICIs are monoclonal antibodies that block the interaction between molecules that normally inhibit the function of effector T cells, ultimately increasing their ability to destroy cancer cells but also causing immune-related adverse events, such as hypophysitis. Ipilimumab, a CTLA-4 blocker, was the first ICI approved from the Food and Drug Administration for advanced melanoma patients in 2011. ⋯ Its pathogenesis remains unknown, although the expression of CTLA-4 and PD-1 on pituitary cells could play a role. The diagnosis is mainly clinical since there are no specific serological markers and MRI findings are subtle. The treatment is based on long-term hormone replacement and does not typically require discontinuation of immunotherapy.
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Diabetic neuropathies are common and their prevalence is rising with the growth in the global prevalence of type 2 diabetes. Several patterns of neuropathy have now been described, with diabetic sensorimotor polyneuropathy (DPN) being the most common. ⋯ Currently, the only available treatments for DPN are optimal glucose control and pain management, whereas interventions, beyond optimizing hyperglycemic control, to address the underlying polyneuropathy are not available. Here we review current treatment options and new literature relating to DPN, with an emphasis on novel and emerging treatments.
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Expert Rev Endocrinol Metab · May 2014
Evaluating the potential utility of kisspeptin to treat reproductive disorders.
The kisspeptins, encoded by the KISS1 gene, are a group of newly discovered peptides, which have been found to play an important regulatory role in human reproduction. Loss of function mutations of kisspeptin or the kisspeptin receptor have been shown to cause pubertal failure; whereas activating mutations cause precocious puberty. Central and peripheral administration of kisspeptin to mammals stimulates gonadotrophin secretion via gonadotrophin releasing hormone (GnRH) stimulation. ⋯ Metabolic state, stress, and other neuropeptides such as neurokinin B (NKB) are associated with changes in kisspeptin's stimulatory action. The conclusions from kisspeptin studies so far have led to the consideration of potential therapeutic applications, which will be discussed. Increasing our understanding of kisspeptin may aid our knowledge and management of infertility, contraception and hormone sensitive conditions.
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Expert Rev Endocrinol Metab · Nov 2012
Research and development in the molecular genetics of pituitary adenomas and related tumors.
Interview by Rona Williamson Constantine A Stratakis received his MD and Doctor of Medical Sciences degrees from the University of Athens (Greece) in 1989 and 1994, respectively; he did predoctoral work at the Unit of Endocrinology, Department of Experimental Pharmacology of the same University and at Hospital Cochin (Paris, France), before joining the Developmental Endocrinology Branch of the then National Institute of Child Health & Human Development (NICHD) at the NIH (MD, USA). He continued his postgraduate medical education at Georgetown University Medical School (DC, USA), where he finished a residency in Pediatrics and two fellowships, in Pediatric Endocrinology, followed by Medical Genetics and Clinical Dysmorphology (in a joint program with the then newly founded National Center for Genomic Research, now NHGRI). Dr Stratakis is Board-certified in Pediatrics, Pediatric Endocrinology and Medical Genetics; after a brief stint as faculty at Georgetown University Department of Pediatrics and the Fairfax Children's Hospital, he joined the Developmental Endocrinology Branch, NICHD, NIH as a Unit Chief in 1996; he continued there as a Senior Investigator and Chief of the Section on Genetics & Endocrinology. ⋯ Dr Stratakis has been the recipient of the 1999 Pharmacia-Endocrine Society Award for Excellence in Published Clinical Research, three NIH Merit Awards and other honors, and has been named Visiting Professor in academic centers around the world. He was awarded the 2009 Ernst Oppenheimer Award of the Endocrine Society. Dr Stratakis has been the Scientific Director of the Eunice Kennedy Shriver National Institute of Child Health & Human Development since 2011.