Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity - data from the EU-AIR

CONTEXT AND OBJECTIVE: Treatment for adrenal insufficiency (AI) remains suboptimal. Despite glucocorticoid replacement, patients with AI have reduced life expectancy and quality of life. This study aimed to describe the spectrum of management of glucocorticoid replacement in patients with AI enrolled in the European Adrenal Insufficiency Registry (EU-AIR). DESIGN, SETTING AND PATIENTS: EU-AIR is a prospective, multinational, multicentre, observational study initiated in August 2012 to monitor the long-term safety of glucocorticoid replacement in routine clinical practice in Germany, the Netherlands, Sweden and the UK (ClinicalTrials.gov identifier: NCT01661387). This analysis included 1166 patients with primary and secondary AI (mean disease duration 16·1 ± 11·6 years) receiving long-term glucocorticoid replacement therapy. MAIN OUTCOME MEASURE: Glucocorticoid type, dose, frequency and treatment regimen were examined. RESULTS: Most patients (87·4%) were receiving hydrocortisone. The most common dose range, taken by 42·2% of patients, was 20 to <25 mg/day; however, 12·6% were receiving doses of ≥30 mg/day. Hydrocortisone was being taken once daily by 5·5%, twice daily by 48·7%, three times daily by 43·6% and four times daily by 2·1%. Patients with primary AI received higher replacement doses than those with secondary AI (23·4 ± 8·9 and 19·6 ± 5·9 mg/day, respectively). Twenty-five different regimens were being used to deliver a daily hydrocortisone dose of 20 mg. CONCLUSIONS: We have shown significant heterogeneity in the type, dose, frequency and timing of glucocorticoid replacement in real-world clinical practice. This reflects dose individualization based on patient symptoms and lifestyle in the absence of data supporting the optimal regimen

Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial

Aim:  The aim of this study was to evaluate the effect on body weight and safety of subcutaneously administered recombinant leptin in obese adults and to evaluate whether the timing of recombinant leptin administration influences efficacy. Methods:  A randomized, double-blind, placebo-controlled, multicentre study was designed, comprising of a 3-week dietary lead-in followed by a 12-week leptin or placebo treatment period. A total of 284 overweight and obese (body mass index 27–37.0 kg/m2) predominantly white (98%) women (66%) and men (34%) with a mean (±s.d.) 46.8 ± 10.4 years of age were randomized into three treatment groups with three matching placebo groups. Recombinant leptin was administered by subcutaneous injection [10 mg/morning, 10 mg/evening or 20 mg/day (10 mg twice daily)]. Patients were counselled at baseline to reduce dietary intake by 2100 kJ/day (500 kcal/day), and dietary advice was reinforced every 2–4 weeks. Results:  No statistically significant change in body weight occurred with recombinant leptin treatment compared with placebo treatment in any treatment group. No clinically significant adverse effects were observed with the exception of an increase in injection-site reactions in patients treated with recombinant leptin (83%) vs. placebo (36%). Conclusions:  Administration of recombinant leptin to an overweight and obese population, in addition to a mildly energy-restricted diet, was not efficacious in terms of weight loss at the doses and schedules studied. The hypothesis that nocturnal administration of recombinant leptin might have a specific effect on weight loss was not supported

Validity and reproducibility of ultrasonography for the measurement of intra-abdominal adipose tissue

OBJECTIVE: We studied the validity and reproducibility of a new abdominal ultrasound protocol for the assessment of intraabdominal adipose tissue. MEASUREMENTS: Intra-abdominal adipose tissue was assessed by CT MRI, anthropometry and ultrasonography on a single day. By ultrasonography the distance between peritoneum and lumbar spine was measured using a strict protocol, including the location of the measurements, pressure on the transducer and respiration. All measurements were repeated after 3 months. RESULTS: The study population consisted of 19 overweight patients with a body mass index (BMI) of 32.9 kg/m(2) (s.d. 3.7), intra-abdominal adipose tissue on CT 140.1 cm(2) (s.d. 55.9), and a mean ultrasound distance of 9.8 cm (s.d. 2.5). There was a strong association between the CT and ultrasonographic measures: Pearson correlation coefficient was 0.81 (P <0.001). The correlation between ultrasound and waist circumference was 0.74 (P <0.001), the correlation between CT and waist circumference was 0.57 (P = 0.01). Ultrasound appeared a good method to diagnose intra-abdominal obesity: the area under the ROC curve was 0.98. During the follow-up period of 3 months, the patients lost on average almost 3 kg of body weight. The correlation coefficient between changes in intra-abdominal adipose tissue assessed by CT and ultrasound was 0.74 (P <0.001). The correlation coefficient of the mean ultrasound distance assessed by two different sonographers at baseline was 0.94 (P <0.001), the mean difference 0.4 cm (s.d. 0.9), and the coefficient of variation 5.4%, indicating good reproducibility of the ultrasound measurements. CONCLUSIONS: The results of this validation study show that abdominal ultrasound, using a strict protocol, is a reliable and reproducible method to assess the amount of intra-abdominal adipose tissue and to diagnose intra-abdominal obesity