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doi: 10.1586/17446651.2013.846213pmid: 30736134
Eliglustat tartrate is a highly specific inhibitor of glucosylceramide synthase, developed for the treatment glucosylceramide-based glycosphingolipidoses. Eliglustat is in late clinical development for Gaucher disease type 1. Phase II and III clinical trials have demonstrated clinical efficacy for eliglustat as a stand-alone agent for newly diagnosed patients that are naïve to prior therapy and for patients who have been previously treated with enzyme replacement therapy. Importantly, the reported toxicity of eliglustat has been limited. Eliglustat will be submitted for the US FDA and EMA review in late 2013. Several structurally unrelated glucosylceramide synthase inhibitors have been identified and are in various stages of development, some of which cross the blood–brain barrier. Targeting glucosylceramide synthesis is also a promising approach for the treatment of type 2 diabetes mellitus, autosomal dominant polycystic kidney disease and certain cancers.
doi: 10.1586/17446651.2013.856137pmid: 30736135
English language case–control studies reporting on the association of thyroid cancer occurrence with smoking and alcohol drinking are summarized. Two independent researchers performed study selection and data extraction. Random effects model was applied and external adjustment was performed to control for important confounders. Twenty reports published between 1987 and 2007 were included in quantitative synthesis. For smoking, mean association was inverse (odds ratio [OR]: 0.785; 95% CI: 0.701–0.879) remaining after adjustment for alcohol drinking; heterogeneity was moderate. For alcohol drinking, mean association was inverse (OR: 0.795; 95% CI: 0.660–0.958) (remaining after adjustment for smoking, OR: 0.832; 95% CI: 0.688–1.007); heterogeneity was large becoming moderate after adjustment. Data from case–control studies identified showed inverse mean association between thyroid cancer occurrence and ever-smoking or ever-drinking alcohol.
doi: 10.1586/17446651.2013.853447pmid: 30736136
With the widespread use of imaging techniques, incidental discovery of clinically unsuspected pituitary adenomas is increasing in frequency and will increase further. The Endocrine Society Task Force on Pituitary Incidentalomas has developed practice guidelines which reflect the best available evidence combined with the opinions of experts in pituitary diseases. For incidental macroadenomas, evidence supporting comprehensive evaluation (for hyperfunction, hypopituitarism and anatomy) and management (whether surgical or careful follow-up) is strong. By contrast, evidence supporting approaches to microadenomas without clinical suggestion of hormonal hypersecretion are relatively weak and practice varies. Developing more evidence will require approaches other than randomized controlled trials, such as comparative effectiveness studies. Incidentalomas represent part of a larger societal issue, that being overdiagnosis and its consequences.
doi: 10.1586/17446651.2013.853449pmid: 30736137
Prader–Willi syndrome (PWS) is a complex genetic disorder characterized by muscular hypotonia, hypogonadism, short stature, hyperphagia, obesity, cognitive disabilities and behavioral problems. Body composition is abnormal and growth hormone (GH) secretion is insufficient with more body fat than lean body mass. In children with PWS treatment with GH improves height, head size, body composition and psychomotor functioning. In adults with PWS treatment with GH improves body composition, physical activity and quality of life. However, restricted diet and regular physical exercise are cornerstone treatments in PWS also during GH treatment. GH treatment should be considered in PWS patients with a genetically confirmed diagnosis. Cognitive disabilities and scoliosis are not contraindications to GH treatment. Adverse effects to GH treatment in PWS are few, but glucose metabolism and changes in respiration must be monitored carefully, especially in individuals with predispositions. GH treatment should be continued as long as benefits outweigh the risks.
doi: 10.1586/17446651.2013.840237pmid: 30736138
Thyroid diseases affect up to 5% of all pregnancies. Adverse pregnancy and neonatal outcomes are increased by maternal thyroid disease and adequate treatment is thought to reduce these risks. Hypothyroidism is commonly treated with levothyroxine, with pregnancy increasing levothyroxine requirements in most women treated for hypothyroidism. Hyperthyroidism is often treated with antithyroid drugs in pregnancy. However, they are not completely safe to use during pregnancy as methimazole increases risk of neonatal malformations and propylthiouracil increases risk of maternal hepatotoxicity. Propylthiouracil is recommended to be used during the first trimester and switch to methimazole is recommended thereafter to reduce risk of hepatotoxicity. The treatment goal for hypothyroidism and hyperthyroidism is to achieve euthyroidism quickly and maintain it throughout pregnancy. Autoimmune thyroiditis and isolated maternal hypothyroxinemia do not currently warrant treatment during pregnancy, unless hypothyroidism ensues. Treatment of thyroid nodules and differentiated thyroid cancer can generally be safely postponed until after delivery.
Elsheikh, Elzafir; Henry, Linda L; Younossi, Zobair M
doi: 10.1586/17446651.2013.846212pmid: 30736139
Nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH) are the most common causes of chronic liver disease in industrialized countries. NAFLD has also been strongly associated with type II diabetes and cardiovascular diseases. This study was a multipurposed review, which included discussion of recent studies investigating the cellular and genetic basis of these diseases, the pathogenesis of NAFLD and the current treatment and management of nonalcoholic steatohepatitis. Currently, maintaining a healthy weight through dietary changes and exercise, the use of insulin-modulating pharmacologic agents for diabetes control and the use of lipid-lowering, anti-oxidants have been the most widely recommended treatments. Inclusion of pathogenic mechanisms in treatment design will allow future therapies to target-specific pathways involved in NAFLD pathogenesis.
Panidis, Dimitrios; Tziomalos, Konstantinos; Papadakis, Efstathios
doi: 10.1586/17446651.2013.853451pmid: 30736140
Polycystic ovary syndrome (PCOS) is frequently characterized by abdominal obesity and insulin resistance, which also represent the hallmarks of the metabolic syndrome (MetS). It is well established that MetS is associated with increased risk for both Type 2 diabetes mellitus and cardiovascular disease (CVD) and accumulating data suggest that PCOS is also a risk factor for Type 2 diabetes mellitus and CVD. Accordingly, the association of PCOS with MetS has major health care implications given also the high prevalence of both disorders. We aimed to critically analyze the major studies that compared the prevalence of MetS between women with PCOS and controls, to discuss the anthropometric, endocrine and metabolic characteristics of PCOS, which are implicated in the pathogenesis of Mets in women with PCOS and to comment on the implications and management of MetS in this population. We thus summarize the evidence regarding the prevalence of MetS in PCOS and discuss the primary determinants driving this association. Current evidence shows that MetS is frequently observed in women with PCOS, but this appears to be mainly due to the more pronounced abdominal obesity in these women and not due to PCOS per se. Lifestyle changes are the treatment of choice for MetS in women with PCOS, whereas pharmacotherapy should be individualized.
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