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Context: No long-term studies have compared centrally acting drugs for treating obesity. Objective: To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss. Design and Setting: A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution. Patients: A total of 174 obese premenopausal women. Intervention: Participants randomly received DEP 75 mg ( n =28), FEN 25 mg ( n =29), MZD 2 mg ( n =29), SIB 15 mg ( n =30), FXT 20 mg ( n =29) or PCB ( n =29) daily over 52 weeks. Diet and physical activity were encouraged. Main Outcome Measures: The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters. Results: Weight loss was greater than PCB (−3.1±4.3 kg) with DEP (−10.0±6.4 kg; P< 0.001), SIB (−9.5±5.9 kg; P< 0.001), FEN (−7.8±6.9 kg; P< 0.01) and MZD (−7.4±4.9 kg; P< 0.01) but not with FXT (−2.5±4.1 kg). Ten (33.3%) women lost⩾5% of their initial weight with PCB, compared with 20 (71.4%; P< 0.001) with DEP, 20 (69%; P< 0.02) with FEN, 21 (72.4%; P< 0.01) with MZD, 22 (73.3%; P< 0.001) with SIB and 10 (35.5%) with FXT. Each medically treated group experienced more adverse events compared with PCB ( P< 0.001). Compared with PCB, constipation was more prevalent with DEP, SIB and MZD ( P< 0.01); anxiety was more prevalent with DEP ( P= 0.01); and irritability occurred more frequently with DEP and FEN ( P= 0.02). Significant improvements in the depression and anxiety scores, binge-eating episodes and quality of life correlated with weight loss. CONCLUSION: The centrally acting drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss in obese premenopausal women, with a satisfactory benefit–risk profile.

Summary We did a cross-sectional analysis of chronic pulmonary obstructive disease (COPD) patients without chronic use of systemic glucocorticoids (CUG). Osteoporosis was found in 51% and bone mineral density (BMD) was correlated with severity of disease. Low levels of vitamin D were found in 94%. All COPD patients may benefit from vitamin D supplementation and screening for low BMD. Introduction Patients with chronic pulmonary obstructive disease have low bone mineral density, caused by chronic use of systemic glucocorticoids and hypovitaminosis D. However, patients without CUG may also have low BMD. Methods We performed a cross-sectional analysis in 49 patients (21 men, 28 postmenopausal women), with COPD without CUG, from Brazil (25° 25' S). Several markers of bone metabolism were measured, plus BMD. Osteoporosis risk factors and history of fractures were investigated. Respiratory function was assessed by venous gasometry, spirometry, and oximetry. BMD results were compared to those of 40 healthy non-smokers controls. Results COPD patients had lower BMD at all sites (p < 0.01). Osteoporosis was observed in 51%. BMD independently correlated with stage of disease (lumbar spine, R = 0.38, p = 0.01; total femur, R = 0.36, p = 0.01; femoral neck, R = 0.40, p < 0.01). Ninety-four percent had low levels of vitamin D (<30 ng/mL) and 67% had secondary hyperparathyroidism. Vitamin D was correlated with oxygen saturation (R = 0.36, p = 0.01), with lower levels in those with saturation <88% (p = 0.01). Conclusion Patients with COPD without CUG have increased risk for osteoporosis. Such patients have hypovitaminosis D, which is correlated with the severity of disease. Screening for low BMD and vitamin D supplementation may be warranted to all COPD patients.

Whether the preoperative use of somatostatin analogues (SA) improves surgical outcomes in acromegaly is still a matter of debate. Objective We conducted a systematic review of randomized, controlled trials that compared the short-term outcomes of preoperative use of SA (Pre-SA) with direct TSS (No-SA) for the treatment of newly diagnosed acromegaly. Methods Embase, Pubmed, Lilacs, and Central Cochrane were used as our data sources. The primary outcomes were no need for any adjuvant treatment 3 months after surgery, based on biochemical results (GH nadir after OGTT <1 μg/L and normal IGF-1 for age and gender), quality of life and mortality. The included trials were analyzed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results A total of 2.099 references were identified and two reviewers independently screened the titles and abstracts. From the 14 potentially eligible studies, four were included and ten were excluded due to lack of randomization or different outcomes. A pool of 261 patients was randomly assigned to Pre-SA or No-SA. Meta-analysis of IGF1 normalization showed a significant difference in favor of Pre-SA (RR 2.47; 95 % CI 1.66, 3.77). Adding a GH nadir on OGTT ≤1 μg/L, we found a RR of 2.15 (95 % CI 1.39, 3.33). Quality of evidence for no need of adjuvant postoperative treatment was moderate, but for improving quality of life was very low and for mortality was absent. Conclusion Pre-SA increases the chance of biochemical control of acromegaly 3 months after TSS in patients harboring GH-secreting pituitary macroadenomas.

ObjectiveTo evaluate the maternal–fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort.MethodsThe prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study,ResultsWe included 194 women with a mean age of 31 (17–45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases.ConclusionsOur findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed.

SummaryTo evaluate bone mineral density (BMD) and morphometric vertebral fractures (MVF) in chronic obstructive pulmonary disease (COPD) patients in comparison with two control groups. BMD was lower in the disease group (DG) and was associated with the worst disease severity and prognosis. The prevalence of MVF was high and greater in the DG than in the control groups.IntroductionChronic obstructive pulmonary disease (COPD) is associated with osteoporosis and vertebral fractures. It is still unclear whether the presence of fractures and changes in bone mineral density (BMD) are associated with disease severity and prognosis. The aim of this study was to evaluate BMD and morphometric vertebral fractures (MVF) in COPD patients in comparison with two control groups and to correlate these parameters with indices of COPD severity (VEF1 and GOLD) and prognosis (BODE).MethodsThis was a cross-sectional study in COPD patients (disease group, DG) who underwent BMD and vertebral fracture assessment (VFA). Two control groups were used: smokers without COPD (smoker group, SG) and healthy never-smoker individuals (never-smoker group, NSG).ResultsThe DG comprised 121 patients (65 women, mean age 67.9 ± 8.6 years). Altered BMD was observed in 88.4% of the patients in the DG, which was more prevalent when compared with the control groups (p < 0.001). The BMD values were lower in the DG than in the control groups (p < 0.05). BMD was associated with the worst disease severity and prognosis (p < 0.05). The prevalence of MVF was high (57.8%) and greater than that in the SG (23.8%) and the NSG (14.8%; p < 0.001). The prevalence of fractures was not associated with disease severity and prognosis.ConclusionsCOPD patients have a higher prevalence of MVF and low BMD, and the latter was associated with the severity and poor prognosis of the disease.

SummaryThis study evaluated the number of comorbidities between two normal values of 25OHD in outpatients during 1 year of 25OHD measurements. Five hundred twenty-nine outpatients were included, patients with 25OHD ≥ 20 and < 30 ng/mL had the higher number of comorbidities, suggesting that for this specific population, 25OHD ≥ 30 ng/mL would be more appropriate.Introduction This study evaluated the comorbidities between two values of 25OHD in outpatients of a tertiary hospital.MethodsThis is a cross-sectional study with measures of 25OHD in 1-year period, excluding 25OHD < 20 and > 50 ng/mL, clinical research participants, and liver disease and chronic renal failure patients. Patients were divided into two groups: group 1 (G1), 25OHD ≥ 20 and < 30 ng/mL; and group 2 (G2), 250HD ≥ 30 and ≤ 50 ng/mL. Medical records were reviewed for demographic, laboratory, and comorbidity data.ResultsFrom 529 outpatients included, 319 were in G1 (53.3 ± 15.8 years, 85% women), mean 25OHD 24.8 ± 2.8 ng/mL; and 210 outpatients in G2 (56.7 ± 16.0 years, 83% women), mean 25OHD was 36.8 ± 4.8 ng/mL. G1 had the higher number of comorbidities, including altered glycemia, dyslipidemia, hypothyroidism, urinary tract diseases, arthropathy, secondary hyperparathyroidism, anemia, and neurological and psychiatric disorders. Osteoporosis and hypothyroidism were more prevalent in G2. After binary logistic regression, the variables age (OR 0.988, CI 0.97–1.00, p = 0.048), osteoporosis (OR 0.54, CI 0.36–0.80, p = 0.003), dyslipidemia (OR 1.61, CI 1.10–2.39, p = 0.015), arthropathy (OR 2.60, CI 1.40–5.10, p = 0.003), anemia (OR 15.41, CI 3.09–280.08, p = 0.008), and neurological and psychiatric diseases (OR 3.78, CI 1.98–7.88, p = 0.001) maintained significance.ConclusionPatients with serum 25OHD ≥ 20 and < 30 ng/mL had higher prevalence of comorbidities compared to ≥ 30 ng/mL.

Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

Abstract Context Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. Objective To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs). Methods This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had IGF-I ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0× ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary score, and maintenance of mean 5-sample GH <1.0 ng/mL. Results The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0× ULN (odds ratio, 126.53; 95% CI, 13.73->999.99; P < .0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (± SE) change in IGF-I of 0.04 ± 0.09× ULN vs 0.83 ± 0.1× ULN (P < .0001); mean (± SE) change in Acromegaly Symptom Diary score of −0.6 ± 1.5 vs 4.6 ± 1.6 (P = .02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) vs 5/18 (27.8%) patients (odds ratio, 16.61; 95% CI, 2.86-181.36; P = .0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs. Conclusion Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.

Purpose: Biochemical tests are required for diagnosing GH-deficiency in children and adults, but controversies remain regarding diagnostic criteria and type of biochemical tests. The aim of the study is to map the clinical practices of GHD diagnosis in children and adults. Methods: The Growth Hormone Research Society members initiated a Delphi survey of the diagnosis of GHD in children and adults. Pediatric (n = 18) and adult (n = 25) endocrinologists from 14 countries participated and rated their extent of agreement with 61 statements using a Likert-type-scale (1–7). Consensus was predefined as ≥ 80% of panelists rating their agreement unidirectionally as either ≥ 5 (agreement) or ≤ 3 (disagreement). Results: The pediatric panel reached consensus on 17 of 29 (59%) statements on diagnosis in children, whereas the adult panel reached consensus on 28 of 32 (88%) statements on adult patients. There was general agreement to test for GHD in an appropriate clinical context and also on the timing of testing for GHD in both children and adults. A subnormal IGF-I level was considered diagnostic in both children and adults with panhypopituitarism. In children, there was consensus to recommend the arginine stimulation test and the glucagon test. The insulin tolerance test (ITT) was considered gold standard in adults and there was also consensus to recommend the macimorelin test. A stimulated GH cut-off < 5μg/l was consistent with severe GHD in children, whereas test-specific cut-offs were recommended in adults. Conclusion: Consensus on the GHD diagnosis was lower in pediatric practice, mainly with respect to choice and interpretation of GH stimulation tests.