Multicenter Evaluation of a New, Fully Automated Androstenedione Electrochemiluminescence Immunoassay: Precision Analysis, Method Comparison, and Determination of Reference Ranges.

BACKGROUND: Androstenedione (ASD) levels can aid diagnosis of hyperandrogenism together with other clinical/laboratory findings. We evaluated performance of the new, automated Elecsys® ASD assay vs an ASD isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) reference measurement procedure and determined reference ranges. METHODS: Repeatability/intermediate precision were assessed using 3 control levels and 5 human serum pools (n = 75 each; Clinical and Laboratory Standards Institute EP05-A3). Method comparisons vs commercially available immunoassays [IMMULITE ASD (Siemens) and LIAISON ASD (DiaSorin)] and an ID-LC-MS/MS measurement procedure method were conducted using 421 serum samples; Passing-Bablok regression and Pearson's correlation coefficients were calculated. Reference ranges and distribution of values associated with polycystic ovary syndrome (PCOS) were determined in five clinical cohorts using samples from several sites/vendors. RESULTS: Repeatability/intermediate precision coefficients of variation across all sites were 2.01% to 3.91% and 2.43% to 4.30%, respectively (mean ASD: 7.80-34.7 nmol/L). The Elecsys ASD assay showed poor agreement with IMMULITE ASD (slope = 0.459; r = 0.856; n = 320), fair agreement with LIAISON ASD (slope = 0.625; r = 0.984; n = 327), and very good agreement with ID-LC-MS/MS (slope = 1.040; r = 0.996; n = 332). Reference ranges (2.5th-97.5th percentiles) were: children (≤8 years; n = 140), <0.525 to 1.81 nmol/L; males (≥18 years; n = 138), 0.979 to 5.32 nmol/L; and postmenopausal females (n = 140), 0.654 to 3.74 nmol/L. Reference range (5th-95th percentiles) for females with fertile cycle (≥18 years; n = 84) was 1.71 to 4.58 nmol/L. The distribution of values (2.5th-97.5th percentiles) in females with PCOS (n = 125) was 2.26 to 12.1 nmol/L. CONCLUSIONS: Elecsys ASD assay demonstrated excellent precision and very good agreement with ID-LC-MS/MS. Reference ranges were established to support results interpretation in routine practice.

High-Dose Vitamin D Supplementation is Necessary After Bariatric Surgery: A Prospective 2-Year Follow-up Study.

BACKGROUND: We assessed the need of vitamin D supplementation to achieve normal 25-hydroxyvitamin D (25[OH]D) levels after bariatric surgery and whether there were differences between laparoscopy sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: A total of 164 morbid obese patients undergoing bariatric surgery from January 2008 to June 2011 were followed for 2 years. Serum levels of 25(OH)D and intact parathyroid hormone (iPTH) were measured preoperatively and at 3, 6, 9, 12, 18, and 24 months after operation. All patients received 400 IU/day of 25(OH)D. Patients received additional supplementation with 16,000 IU of vitamin D3 (calcifediol) every 2 weeks if 25(OH)D serum levels were < 30 ng/mL (intervention group). RESULTS: Ninety-six (58.5 %) patients underwent LSG and 68 (41.5 %) LRYGB. A total of 106 (64.6 %) patients received calcifediol supplementation (62 in the LSG group and 44 in the LRYGB group). Normal 25(OH)D levels at 24 months were recorded in 69 % of patients in the intervention group and in 48.3 % in the non-intervention group. At 24 months, mean 25(OH)D levels in the non-intervention group were significantly lower among LRYGB patients than among LSG patients (P = 0.009). In the intervention group, normal 25(OH)D levels were achieved in 60 % of patients treated with LSG and in 22.2 % of those treated with LRYGB. Secondary hyperparathyroidism was presented in 49 (29.9 %) patients preoperatively but without significant differences in iPTH levels between the two surgical procedures. CONCLUSION: Patients undergoing bariatric surgery should receive high-dose vitamin D supplementation independently of the surgical technique.

Differences in neurohormonal activity partially explain the obesity paradox in patients with heart failure: The role of sympathetic activation.

BACKGROUND: Obese patients with chronic Heart Failure (HF) have better outcome than their lean counterparts, although little is known about the pathophysiology of this obesity paradox. Our aim was to evaluate the hypothesis that patients with chronic HF and obesity (defined as body mass index (BMI)≥30kg/m(2)), may have an attenuated neurohormonal activation in comparison with non-obese patients. METHODS AND RESULTS: The present study is the post-hoc analysis of a cohort of 742 chronic HF patients from a single-center study evaluating sympathetic activation by measuring baseline levels of norepinephrine (NE). Obesity was present in 33% of patients. Higher BMI and obesity were significantly associated with lower NE levels in multivariable linear regression models adjusted for covariates (p<0.001). Addition to NE in multivariate Cox proportional hazard models attenuated the prognostic impact of BMI in terms of outcomes. Finally, when we explored the prognosis impact of raised NE levels (>70th percentile) carrying out a separate analysis in obese and non-obese patients we found that in both groups NE remained a significant independent predictor of poorer outcomes, despite the lower NE levels in patients with chronic HF and obesity: all-cause mortality hazard ratio=2.37 (95% confidence interval, 1.14-4.94) and hazard ratio=1.59 (95% confidence interval, 1.05-2.4) in obese and non-obese respectively; and cardiovascular mortality hazard ratio=3.08 (95% confidence interval, 1.05-9.01) in obese patients and hazard ratio=2.08 (95% confidence interval, 1.42-3.05) in non-obese patients. CONCLUSION: Patients with chronic HF and obesity have significantly lower sympathetic activation. This finding may partially explain the obesity paradox described in chronic HF patients.

Bone health in a prospective cohort of postmenopausal women receiving aromatase inhibitors for early breast cancer.

OBJECTIVE: Baseline bone health in postmenopausal women is poorly characterized in prospective series of early breast cancer (EBC) patients candidates to aromatase inhibitor (AI) therapy. Our objective is to comprehensively evaluate bone health in a prospective clinical cohort of patients recruited prior to adjuvant AI therapy, with the aim of establishing potential AI impact on bone loss and fractures. METHODS: From January 2006 to April 2010, we consecutively included 343 women with EBC who were about to start adjuvant AI therapy. Participants were assessed at baseline (before AI initiation) and at 3 months, with annual assessments thereafter. Bone mineral density (BMD), spine X-ray, bone metabolism (vitamin D [25(OH)D], bone turnover markers [BTM]), arthralgia and quality of life are measured. RESULTS: Mean age was 61.9 years; 197 (57.4%) had been previously treated with tamoxifen; 145 (42.3%) were taking exemestane, 187 (54.5%) letrozole, and 11 (3.2%) anastrozole. Analysis of baseline data shows only 59 women (17.7%) had normal BMD; 200 (60.1%) had osteopenia and 74 (22.2%) had osteoporosis; 39 women (11.4%) had a prevalent fracture, 293 (89.1%) had 25(OH)D insufficiency (<30 ng/ml), and 61 (18.5%) severe deficiency (<10 ng/ml). Low 25(OH)D concentrations were associated with lower BMD and 233 (67.9%) participants had some degree of arthralgia. CONCLUSIONS: Low bone mass, prevalent fractures and vitamin D insufficiency were highly prevalent among candidates to adjuvant AI for EBC. Therefore, it is crucial to assess BMD, prevalent fractures and 25(OH)D concentrations before starting AI therapy and during follow-up.

[Bone mass loss after sleeve gastrectomy: a prospective comparative study with gastric bypass]. / Pérdida de masa ósea tras gastrectomía tubular: estudio prospectivo comparativo con el bypass gástrico.

INTRODUCTION: Bariatric surgery is the most effective option for the treatment of patients with a high risk of complications due to their obesity. However, it brings about a series of changes in calcium and vitamin D metabolism and an increase in resorption which lead to a loss of bone mass. AIM: The objective of this study is to compare sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) as regards loss of bone mass using bone densitometry and bone remodelling markers. PATIENTS AND METHODS: Fifteen women with morbid obesity were included, 8 by SG and 7 by RYGB, with a mean age of 47.8+/-9 and mean body mass index 43.3+/-3.4. Bone mass measurements were made on the lumbar spine, femur and distal radius, and the bone remodelling markers N-telopeptide (NTx) and bone alkaline phosphatase (BALP), as well as vitamin D levels before and 12 months after surgery. RESULTS: A significant bone mass loss was observed was observed with SG and RYGB, in the lumbar spine and hip, whilst no differences were observed in the radial. The percentage bone mass loss was less in the column and femur after SG than with RYGB, although it did not reach statistical significance, 4.6%+/-4.4 (mean+/-SD) and 6.3%+/-5.4 (mean+/-SD), respectively. At 12 months the Ntx increased for both types of surgery, and the BAP was only increased for SG. CONCLUSION: SG causes less, although not significant, bone mass loss compared to RYGB.