BACKGROUND The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P =0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. CONCLUSIONS In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.)

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UBCLINICAL OR "MILD" THYROID disease is a common disorder, particularly in middle-aged and elderly individuals. 1 Greater sensitivity of assays and more frequent assessment of serum thyroidstimulating hormone (TSH) levels have resulted in more patients requiring interpretation of abnormal thyroid function test results. However, controversy surrounds the definition, clinical importance, and necessity for prompt diagnosis and treatment of subclinical thyroid disease. Previous review articles 2-6 and position statements 7,8 differ in their conclusions and recommendations, often a consequence of difficulties in interpreting inadequate and conflicting data. In the midst of this uncertainty, clinicians still desire expert guidance for the diagnosis and management of subclinical thyroid disease.

Extra-adrenal pheochromocytomas may arise in any portion of the paraganglion system, although they most commonly occur below the diaphragm. The most common site of occurrence of extra-adrenal pheochromocytoma is the superior para-aortic region between the diaphragm and lower renal poles. Although the traditional teaching has been that 10% of all pheochromocytomas are at extra-adrenal sites, this may be an underestimation. Extra-adrenal pheochromocytomas probably represent at least 15% of adult and 30% of childhood pheochromocytomas. They may be malignant in up to 40% of the cases, although conflicting data add to the uncertainty of this point. Patients with tumors arising at extra-adrenal sites commonly present with headache, palpitations, sweating and hypertension. The diagnosis is most often confirmed by demonstrating increased catecholamine production, usually by measurement of urinary catecholamines and/or their metabolites. CT scanning is presently the imaging procedure of choice for localization. The roles of MRI and 131I-MIBG scintigraphy in the localization process are still being determined. Thorough preoperative pharmacological preparation, attentive intraoperative monitoring and aggressive surgical therapy all have an important role in achieving the safest and most successful outcome. Complete surgical excision is the treatment of choice for primary extra-adrenal pheochromocytoma as well as recurrent or metastatic disease. When residual tumor cannot be resected, medical therapy for symptomatic relief is preferred, since radiotherapy and chemotherapy have limited effectiveness. Extra-adrenal pheochromocytomas are more likely to recur and to metastasize than their adrenal counterparts, making lifelong followup with annual determinations of catecholamine production essential.

The American Thyroid Association recommends that adults be screened for thyroid dysfunction by measurement of the serum thyrotropin concentration, beginning at age 35 years and every 5 years thereafter. The indication for screening is particularly compelling in women, but it can also be justified in men as a relatively cost-effective measure in the context of the periodic health examination. Individuals with symptoms and signs potentially attributable to thyroid dysfunction and those with risk factors for its development may require more frequent serum thyrotropin testing.