Endocrine Diseases

These NCCN Guidelines Insights highlight the important updates/changes specific to the management of metastatic breast cancer in the 2012 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer. These changes/updates include the issue of retesting of biomarkers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) on recurrent disease, new information regarding first-line combination endocrine therapy for metastatic disease, a new section on monitoring of patients with metastatic disease, and new information on endocrine therapy combined with an mTOR inhibitor as a subsequent therapeutic option.

Observational data indicate that newer vitamin D compounds such as paricalcitol can suppress serum intact parathyroid hormone (iPTH) and reduce proteinuria in patients with CKD. To systematically evaluate the efficacy and safety of paricalcitol for CKD, we conducted a meta-analysis of the published randomized controlled trials (RCTs).|MEDLINE, Embase, the Cochrane Library, and article reference lists were searched for RCTs that compared paricalcitol with placebo in the treatment of patients with stage 2-5 CKD. The quality of the studies was evaluated using the Jadad method. The results are summarized as risk ratios (RRs) for dichotomous outcomes or mean differences for continuous outcomes.|Nine studies (832 patients) were included. Compared with placebo, paricalcitol suppressed serum iPTH (RR, 6.37; 95% confidence interval [95% CI], 4.64-8.74; P<0.001) and reduced proteinuria (RR, 1.68; 95% CI, 1.25-2.25; P<0.001). Compared with the control group, the RR for hypercalcemia associated

Moderate differences in efficacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could affect treatment choices. We sought any such differences.|We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plus-anthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44,000); one anthracycline-based regimen versus another (n=7000) or versus cyclophosphamide, methotrexate, and fluorouracil (CMF; n=18,000); and polychemotherapy versus no chemotherapy (n=32,000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported.|In trials adding four separate cycles of a taxane to a fixed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 086, SE 004, two-sided significance [2p]

Although endometrial adenocarcinoma is a common gynaecological cancer, a comparatively small proportion of patients present with, or develop, recurrent or advanced disease. However, for those women whose disease does progress or recur the prognosis is poor and the best treatment is yet to be identified. Co-morbidity, including obesity and cardiac disease, and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents.|To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma.|Systematic searches of MEDLINE, EMBASE, CENTRAL and the Cochrane Gynaecological Cancer specialist trials register were conducted to identify all eligible randomised controlled trials (RCTs).Databases were searched from 1966 to January 2012. Literature searches were supplemented with searches of relevant trials registers and conference proceedings.|RCTs

22025785 2011 10 25 2012 02 16 2012 11 02 1935-5548 34 11 Nov Diabetes Care 2477-85 10.2337/dc11-1723 University of Southern California Keck School of Medicine, Los Angeles, California, USA. Peters Anne A Laffel Lori L American Diabetes Association

Graves' Disease (GD) is a common and complex disorder, with a strong hereditary component. IL-17F is a potent cytokine and a potential contributor to the etiology of various human autoimmune diseases. In the present study, we focused on the relationship between polymorphisms in the IL-17F gene and GD susceptibility through a case-control association study in two independent Chinese cohorts.|Our pilot study was performed on a cohort from Shanghai, which included 757 GD patients and 741 healthy controls. Our replication cohort was from Xiamen, consisting of 434 GD patients and 420 healthy controls. We selected four tag SNPs (rs763780, rs2397084, rs9463772 and rs761167) within the IL-17F gene to conduct a genotyping analysis.|In the Shanghai cohort, the rs9463772 polymorphism showed a significant association with GD and Graves' Disease-associated Ophthalmopathy (GO) patients (P(allele)=710(-5) and 7.410(-3) for GD and GO patients, respectively). The rs763780 polymorphism was found to

Drug-induced valvular heart disease (DIVHD) was first described in the 1960s. Initially, associations with ergot derivatives used for migraine prevention, or with anorectic drugs, were described. Drugs used for the treatment of Parkinson's disease and endocrine diseases, like hyperprolactinemia, may also induce VHD. More recently, the use of 3,4-methylendioxymetamphetamine (MDMA, 'Ecstasy') and benfluorexhave been found to be associated with DIVHD. Although some of these drugs were withdrawn from the market, several cases of patients requiring valve surgery even years after the cessation of therapy have been reported. DIVHD is not infrequent, may be severe, and has been described in association with several drugs. Even after drug cessation, long-term implications of this type of VHD may persist. The present review underlines the need for a careful evaluation of the associated clinical and echocardiographic risk factors to allow early recognition so as not to delay appropriate

The heart hypertrophies in response to developmental signals as well as increased workload. Although adult-onset hypertrophy can ultimately lead to disease, cardiac hypertrophy is not necessarily maladaptive and can even be beneficial. Progress has been made in our understanding of the structural and molecular characteristics of physiological cardiac hypertrophy, as well as of the endocrine effectors and associated signalling pathways that regulate it. Physiological hypertrophy is initiated by finite signals, which include growth hormones (such as thyroid hormone, insulin, insulin-like growth factor 1 and vascular endothelial growth factor) and mechanical forces that converge on a limited number of intracellular signalling pathways (such as PI3K, AKT, AMP-activated protein kinase and mTOR) to affect gene transcription, protein translation and metabolism. Harnessing adaptive signalling mediators to reinvigorate the diseased heart could have important medical ramifications.

Therapies directed at endocrine receptors and human epidermal growth factor receptor 2 are important treatment options for patients with breast cancer; however, drug resistance and subsequent disease progression in patients with advanced disease is inevitable. The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and proliferation implicated in the cellular processes that lead to the uncontrolled growth of cancer cells. Hence, overactivation of the mTOR pathway may also represent a key process in the development of resistance to these therapies, and interrupting this signaling cascade may alleviate resistance and help restore drug sensitivity. A number of agents that target the mTOR pathway have shown potent antitumorigenic effects in vitro, and several agents have also shown promise in treating patients with breast cancer. Everolimus and temsirolimus are the most clinically advanced agents in this class, with recent data from the BOLERO-2 study indicating

Subclinical hypothyroidism (SH) is quite common in children and adolescents. The natural history of this condition and the potential effects of replacement therapy need to be known to properly manage SH. The aim of this review is to analyze: i) the spontaneous evolution of SH, in terms of the rate of reversion to euthyroidism, the persistence of SH, or the progression to over hypothyroidism; and ii) the effects of replacement therapy, with respect to auxological data, thyroid volume, and neuropsychological functions.|We systematically searched PubMed, Cochrane, and EMBASE (1990-2012) and identified 39 potentially relevant articles of which only 15 articles were suitable to be included.|SH in children is a remitting process with a low risk of evolution toward overt hypothyroidism. Most of the subjects reverted to euthyroidism or remained SH, with a rate of evolution toward overt hypothyroidism ranging between 0 and 28.8%, being 50% in only one study (nine articles). The initial

Reviews the evidence for and against hundreds of preventive health services, recommending tests, and counseling interventions when evidence exists that it is effective.

Primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk: an Endocrine Society clinical practice guideline.

NGC is the National Guideline Clearinghouse.