Objective: Cushing's disease (CD) is a rare endocrine disorder characterized by excess secretion of ACTH due to a pituitary adenoma. Current treatment options are limited and may pose additional risks. A literature review was conducted to assess the holistic burden of CD. Design: Studies published in English were evaluated to address questions regarding the epidemiology of CD, time to diagnosis, health-related quality of life (HRQoL), treatment outcomes, mortality, prevalence of comorbidities at diagnosis, and reversibility of comorbidities following the treatment. Methods: A two-stage literature search was performed in Medline, EMBASE, and Science Citation Index, using keywords related to the epidemiology, treatment, and outcomes of CD: i) articles published from 2000 to 2012 were identified and ii) an additional hand search (all years) was conducted on the basis of bibliography of identified articles. Results: At the time of diagnosis, 58-85% of patients have hypertension, 32-41% are obese, 20-47% have diabetes mellitus, 50-81% have major depression, 31-50% have osteoporosis, and 38-71% have dyslipidemia. Remission rates following transsphenoidal surgery (TSS) are high when performed by expert pituitary surgeons (rates of 65-90%), but the potential for relapse remains (rates of 5-36%). Although some complications can be partially reversed, time to reversal can take years. The HRQoL of patients with CD also remains severely compromised after remission. Conclusions: These findings highlight the significant burden associated with CD. As current treatment options may not fully reverse the burden of chronic hypercortisolism, there is a need for both improved diagnostic tools to reduce the time to diagnosis and effective therapy, particularly a targeted medical therapy.

Although acromegaly is a rare disease, the clinical, economic and health-related quality of life (HRQoL) burden is considerable due to the broad spectrum of comorbidities as well as the need for lifelong management. We performed a comprehensive literature review of the past 12 years (1998–2010) to determine the benefit of disease control (defined as a growth hormone [GH] concentration <2.5 μg/l and insulin-like growth factor [IGF]-1 normal for age) on clinical, HRQoL, and economic outcomes. Increased GH and IGF-1 levels and low frequency of somatostatin analogue use directly predicted increased mortality risk. Clinical outcome measures that may improve with disease control include joint articular cartilage thickness, vertebral fractures, left ventricular function, exercise capacity and endurance, lipid profile, and obstructive apnea events. Some evidence suggests an association between controlled disease and improved HRQoL. Total direct treatment costs were higher for patients with uncontrolled compared to controlled disease. Costs incurred for management of comorbidities, and indirect cost could further add to treatment costs. Optimizing disease control in patients with acromegaly appears to improve outcomes. Future studies need to evaluate clinical outcomes, as well as HRQoL and comprehensive economic outcomes achieved with controlled disease.

BackgroundA network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the relative efficacy and safety of dolutegravir (DTG) versus third agents currently recommended by guidelines, including ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r), raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1–infected patients.MethodsA systematic review of published literature was conducted to identify phase 3/4 randomized controlled clinical trials (up to August 2013) including at least one third agent of interest in combination with a backbone nucleoside reverse transcriptase inhibitor (NRTI) regimen. Bayesian fixed-effect network meta-analysis models adjusting for the type of nucleoside reverse transcriptase inhibitor backbone (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or abacavir/lamivudine [ABC/3TC]) were used to evaluate week 48 efficacy (HIV-RNA suppression to <50 copies/mL and change in CD4+ cells/µL) and safety (lipid changes, adverse events, and discontinuations due to adverse events) of DTG relative to all other treatments. Sensitivity analyses assessing the impact of NRTI treatment adjustment and random-effects models were performed.ResultsThirty-one studies including 17,000 patients were combined in the analysis. Adjusting for the effect of NRTI backbone, treatment with DTG resulted in significantly higher odds of virologic suppression (HIV RNA<50 copies/mL) and increase in CD4+ cells/µL versus ATV/r, DRV/r, EFV, LPV/r, and RPV. Dolutegravir had better or equivalent changes in total cholesterol, LDL, triglycerides, and lower odds of adverse events and discontinuation due to adverse events compared to all treatments. Random-effects and unadjusted models resulted in similar conclusions.ConclusionThree clinical trials of DTG have demonstrated comparable or superior efficacy and safety to DRV, RAL, and EFV in HIV-1–infected treatment-naive patients. This network meta-analysis suggests DTG is also favorable or comparable to other commonly used third agents (ATV/r, LPV/r, RPV, and EVG/c).