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Background Circadian rhythm is altered in individuals with obesity and insulin resistance, showing a smaller amplitude, less stability, and increased intradaily variation. Objective We compared reproducibility of circadian-rhythm parameters over time and under free-living vs. controlled conditions in participants with obesity and pre-diabetes after 2- and 3-year weight-loss maintenance during the 3-year PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study. Associations of obesity and insulin resistance with circadian-rhythm parameters were assessed. Subjects and methods Circadian-rhythm parameters were determined using continuous wrist-temperature measurements in free-living environments at year 2 (n = 24; age 56.8 +/- 10.3 y; body mass index (BMI) = 30 +/- 3.9 kg/m(2); homeostatic model assessment of insulin resistance (HOMA-IR) 2.4 +/- 1.1), at year 3 (n = 97; age 61.7 +/- 7.8; BMI = 29.7 +/- 3.9; HOMA-IR 2.9 +/- 2.1), and at year 3 in a controlled condition (n = 38; age 63.4 +/- 6.7; BMI = 28.7 +/- 3.9; HOMA-IR 3.8 +/- 1.4). Reproducibility was assessed by analyzing repeatability coefficients (CR), differences, and associations, over time as well as between conditions. Associations of BMI and HOMA-IR with circadian-rhythm parameters were assessed at y-3 in both conditions using factor analysis, followed by Pearson's correlations. Results Reproducibility of circadian-rhythm parameters over time in the free-living environments was high (CR 0.002-5.26; no significant differences; associated amplitudes r = 0.57; p < 0.01). In contrast, reproducibility between different conditions was low (CR 0.02-11.36; significant differences between most parameters (p < 0.05); yet associated amplitudes r = 0.59; p < 0.01). In the controlled vs. free-living condition circadian-rhythm was more stable; BMI and HOMA-IR were associated with the physiological amplitude-related parameters (r = -0.45; p < 0.01; r = -0.33; p < 0.05). In the free-living environment, BMI and behavioral circadian-rhythm parameters indicating circadian alignment, contributed most to the explained variation (47.1%), and were inversely associated (r = -0.22; p < 0.05), while HOMA-IR was inversely associated with stability-related circadian-rhythm parameters (r = -0.21; p < 0.05). Conclusions Circadian rhythm was highly reproducible over time in the free-living environments, yet different under different conditions, being more stable in the controlled condition. BMI may play a significant role in circadian alignment and vice versa in the free-living environment.

Introduction: Lipedema is an abnormal deposit of subcutaneous fat most often involving the lower limbs symmetrically. The physiopathology is poorly understood, but its peak of the almost exclusivel...

Objective Hair cortisol (HF) and cortisone (HE) measurements reflect tissular exposure to cortisol over months and are increased in overt Cushing’s syndrome (CS). No data is available in mild CS. We compared the diagnostic performance of HF and HE between patients with overt or mild CS. Design Single centre retrospective study. Methods HF&HE were measured by LC-MS/MS in 48 consecutive adult females with Cushing’s disease (CD), ectopic ACTH syndrome, secreting adenomas and carcinomas, and adrenal incidentalomas. All had impaired dexamethasone suppression tests. Overt CS (n = 25) was diagnosed in front of specific symptoms, a mean UFC (>1.5 ULN) and increased midnight serum cortisol or salivary cortisol. Mild CS (n = 23) was diagnosed in patients lacking specific symptoms and displaying at least one additional biological abnormality including mildly increased UFC (≤1.5 ULN), increased midnight serum cortisol or salivary cortisol and suppressed plasma ACTH in patients with adrenal tumours. In this study, 84 healthy subjects and obese patients served as controls. Results HF and HE showed roughly similar performance in overt CS (92 and 100% sensitivity, 91 and 99% specificity, respectively). HF and HE were lower in mild CS but higher than in controls (P < 0.01). HE was correlated with midnight serum cortisol (P < 0.02) and volume of adrenal incidentalomas (P < 0.04) but not with UFC. HF and HE had 59% and 68% sensitivity, and 79 and 94% specificity, respectively, for the diagnosis of mild CS. Contrary to UFC, both HF and HE were in the range of overt CS in 11/23 patients with mild CS. Patients with mild CS and increased HE required more antihypertensive treatments and showed worser lipid profiles than patients with normal HE. Conclusions HF and HE measurement performed better in overt than in mild CS but is a useful adjunct to diagnose mild CS and to identify adrenocortical incidentalomas responsible for excessive cortisol exposure.

Bone mineral density (BMD) declines in the initial years after bariatric surgery, but long-term skeletal effects are unclear and comparisons between sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are rare. An observational longitudinal study of obese patients undergoing SG or RYGB was performed. Whole-body (WB) BMD, along with BMD of the total hip (TH), femoral neck (FN), and lumbar spine (LS), was measured by dual-energy X-ray absorptiometry (DXA) before surgery and yearly thereafter for 4 years. Calciotropic hormones were also measured. Forty-seven patients undergoing RYGB surgery and 28 patients undergoing SG were included. Four years after RYGB, BMD declined by 2.8 ± 5.8% in LS, 8.6 ± 5% in FN, 10.9 ± 6.3% in TH, and 4.2 ± 6.2% in WB, relative to baseline. For SG, BMD declined by 8.1 ± 5.5% in FN, 7.7 ± 6% in TH, 2.0 ± 7.2% in LS, and 2.5 ± 6.4% in WB after 4 years, relative to baseline. Vitamin D levels increased with supplementation in both groups. Whereas parathyroid hormone levels increased slightly in the RYGB group, they decreased modestly in the SG group (P

Patients with obesity are known to exhibit gut microbiota dysbiosis and memory deficits. Bariatric surgery (BS) is currently the most efficient anti-obesity treatment and may improve both gut dysbiosis and cognition. However, no study has investigated association between changes of gut microbiota and cognitive function after BS. We prospectively evaluated 13 obese patients on anthropometric data, memory functions, and gut microbiota-mycobiota before and six months after BS. The Rey Auditory Verbal Learning Test (AVLT) and the symbol span (SS) of the Weschler Memory Scale were used to assess verbal and working memory, respectively. Fecal microbiota and mycobiota were longitudinally analyzed by 16S and ITS2 rRNA sequencing respectively. AVLT and SS scores were significantly improved after BS (AVLT scores: 9.7 ± 1.7 vs. 11.2 ± 1.9, p = 0.02, and SS scores: 9.7 ± 23.0 vs. 11.6 ± 2.9, p = 0.05). An increase in bacterial alpha-diversity, and Ruminococcaceae, Prevotella, Agaricus, Rhodotorula, Dipodascus, Malassezia, and Mucor were significantly associated with AVLT score improvement after BS, while an increase in Prevotella and a decrease in Clostridium, Akkermansia,&nbsp, Dipodascus and Candida were linked to SS scores improvement. We identified several changes in the microbial communities that differ according to the improvement of either the verbal or working memories, suggesting a complex gut-brain-axis that evolves after BS.

An unfavorable lipid profile and being overweight are known mediators in the development of cardiovascular disease (CVD) risk. The effect of diet, particularly high in protein, remains under discussion. Therefore, this study examines the effects of a high-protein (HP) diet on cardiometabolic health and vascular function (i.e., endothelial function, arterial stiffness, and retinal microvascular structure), and the possible association with plasma endocannabinoids and endocannabinoid-related compounds in overweight participants. Thirty-eight participants (64.5 ± 5.9 (mean ± SD) years, body mass index (BMI) 28.9 ± 4.0 kg/m2) were measured for 48 h in a respiration chamber after body-weight maintenance for approximately 34 months following weight reduction. Diets with either a HP (n = 20) or moderate protein (MP, n = 18) content (25%/45%/30% vs. 15%/55%/30% protein/carbohydrate/fat) were provided in energy balance. Validated markers for cardiometabolic health (i.e., office blood pressure (BP) and serum lipoprotein concentrations) and vascular function (i.e., brachial artery flow-mediated vasodilation, pulse wave analysis and velocity, and retinal microvascular calibers) were measured before and after those 48 h. Additionally, 24 h ambulatory BP, plasma anandamide (AEA), 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and pregnenolone (PREG) were analyzed throughout the day. Office and ambulatory BP, serum lipoprotein concentrations, and vascular function markers were not different between the groups. Only heart rate (HR) was higher in the HP group. HR was positively associated with OEA, while OEA and PEA were also positively associated with total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol concentrations. Vascular function markers were not associated with endocannabinoids (or endocannabinoid-related substances). In conclusion, the HP diet did not affect cardiometabolic health and vascular function in overweight participants after completing a weight-loss intervention. Furthermore, our data indicate a possible association between OEA and PEA with TC and LDL cholesterol.

Background: Weight loss has been associated with adaptations in energy expenditure. Identifying factors that counteract these adaptations are important for long-term weight loss and weight maintenance.Objective: The aim of this study was to investigate whether increased protein/carbohydrate ratio would reduce adaptive thermogenesis (AT) and the expected positive energy balance (EB) during weight maintenance after weight loss in participants with prediabetes in the postobese state.Methods: In 38 participants, the effects of 2 diets differing in protein/carbohydrate ratio on energy expenditure and respiratory quotient (RQ) were assessed during 48-h respiration chamber measurements ∼34 mo after weight loss. Participants consumed a high-protein (HP) diet (n = 20; 13 women/7 men; age: 64.0 ± 6.2 y; BMI: 28.9 ± 4.0 kg/m 2) with 25:45:30% or a moderate-protein (MP) diet (n = 18; 9 women/9 men; age: 65.1 ± 5.8 y; BMI: 29.0 ± 3.8 kg/m 2) with 15:55:30% of energy from protein:carbohydrate:fat. Predicted resting energy expenditure (REEp) was calculated based on fat-free mass and fat mass. AT was assessed by subtracting measured resting energy expenditure (REE) from REEp. The main outcomes included differences in components of energy expenditure, substrate oxidation, and AT between groups.Results: EB (MP = 0.2 ± 0.9 MJ/d; HP = -0.5 ± 0.9 MJ/d) and RQ (MP = 0.84 ± 0.02; HP = 0.82 ± 0.02) were reduced and REE (MP: 7.3 ± 0.2 MJ/d compared with HP: 7.8 ± 0.2 MJ/d) was increased in the HP group compared with the MP group (P < 0.05). REE was not different from REEp in the HP group, whereas REE was lower than REEp in the MP group (P < 0.05). Furthermore, EB was positively related to AT (rs = 0.74; P < 0.001) and RQ (rs = 0.47; P < 0.01) in the whole group of participants.Conclusions: In conclusion, an HP diet compared with an MP diet led to a negative EB and counteracted AT ∼34 mo after weight loss, in participants with prediabetes in the postobese state. These results indicate the relevance of compliance to an increased protein/carbohydrate ratio for long-term weight maintenance after weight loss. The trial was registered at clinicaltrials.gov as NCT01777893.

Favorable effects of a high-protein/moderate-carbohydrate (HP/MCHO) diet after weight loss on body weight management have been shown. To extend these findings, associations between perception of hunger and satiety with endocannabinoids, and with glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) were assessed. At approximately 34 months after weight loss, 22 female and 16 male participants (mean age 64.5 &plusmn, 5.9 years, body mass index (BMI) 28.9 &plusmn, 3.9 kg/m2) completed a 48 h respiration chamber study. Participants were fed in energy balance with a HP/MCHO diet with 25%:45%:30% or a moderate-protein/high-carbohydrate (MP/HCHO) diet with 15%:55%:30% of energy from protein:carbohydrate:fat. Endocannabinoids and related compounds, relevant postprandial hormones (GLP-1, PYY), hunger, satiety, and ad libitum food intake were assessed. HP/MCHO versus MP/HCHO reduced hunger perception. The lower decremental area under the curve (dAUC) for hunger in the HP/MCHO diet (&minus, 56.6% compared to MP, p &lt, 0.05) was associated with the higher AUC for 2-arachidonoylglycerol (2-AG) concentrations (p &lt, 0.05). Hunger was inversely associated with PYY in the HP/MCHO group (r = &minus, 0.7, p &lt, 0.01). Ad libitum food intake, homeostatic model assessment for insulin resistance (HOMA-IR) and incremental AUCs for gut peptides were not different between conditions. HP/MCHO versus MP/HCHO diet-induced reduction in hunger was present after 34 months weight maintenance in the post-obese state. HP/MCHO diet-induced decrease of hunger is suggested to interact with increased 2-AG and PYY concentrations.

Bariatric surgery is considered to be the most effective treatment of morbid obesity. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are the most popular procedures. We evaluated nutritional status, micro- and macronutrient intake, and oral hydration in patients before and regularly during 1 year after RYGBP and SG. All patients that had been through bariatric surgery with at least 1-year post-surgery were retrospectively included in the study. All participants were evaluated once during the 2 months before the surgery and at 1, 3, 6, and 12 months after surgery. Clinical and biological evaluations as well as dietary investigations were performed. Fifty-seven patients were included in this study (28 RYGBP and 29 SG). Patients in the RYGBP group had significantly higher body weight (132.3 ± 22 versus 122.2 ± 22.2 kg, p = 0.039) than patients in the SG group. Before surgery, total energy intake, oral hydration, and vitamin and mineral intakes were not different between the two groups. RYGBP and SG induced significant similar excess weight loss 1 year after surgery, 48.6 29.8% and 57.6 27.6% of body weight respectively. Energy intake significantly decreased 1 month after surgery and slightly increased from 1 to 12 months without reaching baseline intake levels. Macronutrient repartition did not change during follow-up. Oral hydration significantly decreased after RYGBP (− 58%) and showed a trend to be decreased after SG (− 49%). Sixty-five percent of patients still had vitamin D deficiency 1 year after surgery. Whatever the type of surgery, more than 20% had some vitamin deficiency 1 month after surgery. Calories intake decreases after bariatric surgery, whatever the type of procedure. In addition, the prevalence of vitamin deficiency is high after bariatric surgery. Lastly, oral hydration is importantly decreased after bariatric surgery, especially after RYGBP.

Dietary protein is effective for body-weight management, in that it promotes satiety, energy expenditure, and changes body-composition in favor of fat-free body mass. With respect to body-weight management, the effects of diets varying in protein differ according to energy balance. During energy restriction, sustaining protein intake at the level of requirement appears to be sufficient to aid body weight loss and fat loss. An additional increase of protein intake does not induce a larger loss of body weight, but can be effective to maintain a larger amount of fat-free mass. Protein induced satiety is likely a combined expression with direct and indirect effects of elevated plasma amino acid and anorexigenic hormone concentrations, increased diet-induced thermogenesis, and ketogenic state, all feed-back on the central nervous system. The decline in energy expenditure and sleeping metabolic rate as a result of body weight loss is less on a high-protein than on a medium-protein diet. In addition, higher rates of energy expenditure have been observed as acute responses to energy-balanced high-protein diets. In energy balance, high protein diets may be beneficial to prevent the development of a positive energy balance, whereas low-protein diets may facilitate this. High protein-low carbohydrate diets may be favorable for the control of intrahepatic triglyceride IHTG in healthy humans, likely as a result of combined effects involving changes in protein and carbohydrate intake. Body weight loss and subsequent weight maintenance usually shows favorable effects in relation to insulin sensitivity, although some risks may be present. Promotion of insulin sensitivity beyond its effect on body-weight loss and subsequent body-weight maintenance seems unlikely. In conclusion, higher-protein diets may reduce overweight and obesity, yet whether high-protein diets, beyond their effect on body-weight management, contribute to prevention of increases in non-alcoholic fatty liver disease NAFLD, type 2 diabetes and cardiovascular diseases is inconclusive.

Introduction Although it is known that the prevalence of obesity is high in deprived patients, the link between deprivation and obesity, and the impact of deprivation on compliance and efficacy of a lifestyle intervention program are not known. Materials and methods Deprivation was assessed in 40 patients (23 Females, mean±SD age: 49±17 years) from the diabetology department and 140 patients (101 Females, age: 50±15 years) from the nutrition department of Bordeaux University hospital. Eighty-seven patients suffering from obesity were evaluated before and after a tailored, multidisciplinary lifestyle intervention. Deprivation was assessed using EPICES scores. Deprivation was defined with an EPICES score > 30. Results Deprived patients suffering from obesity had significantly higher current (43.8 ±8.4 versus 40.9 ± 5.5 kg/m2, p = 0,02) and maximal BMI (46.1± 8.6 versus 42.3± 5.2 kg/m2, p = 0.002) compared to non-deprived obese. Percentage of body weight loss was not different according to deprivation (4.74 ± 0.75 versus 4.65 ± 1.04%, p = 0.9). EPICES scores were not different according to adherence to lifestyle intervention program (20.5 ± 8.5 versus 29.9 ± 3.9 versus 29.0 ±2.5, no follow up versus partial follow up versus total follow up, p = 0,58). Conclusion Deprived patients suffering from obesity have a more serious disease than non-deprived patients. However, neither compliance to the lifestyle intervention program nor body weight loss differed between deprived patients with obesity and non-deprived ones. Deprivation should not be a limitation when enrolling patients with obesity in lifestyle intervention programs.

Background Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood. Design and methods A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB ≥2.0 mg weekly. Results Ninety-two patients (50 F, 42 M) were analyzed. At diagnosis, most had macroprolactinomas (82.6%); males were significantly older than females (P=0.0003) and presented with a more aggressive disease. A genetic basis was identified in 12 patients. Thirty-six patients (39.1%) received only medical therapy, most underwent surgery (60.9%, including multiple interventions in 10.9%), and 14.1% received postoperative radiotherapy. Eight patients developed late CAB resistance (8.7%). The median maximal weekly dose of CAB (CABmax/w) was 3.5 mg (2.0–10.5). Despite a higher CABmax/w in patients treated with multimodal therapy (P=0.003 vs exclusive pharmacological treatment), a debulking effect of surgery was shown in 14 patients, with a higher rate of PRL control (P=0.006) and a significant reduction in CABmax/w (P=0.001) postoperatively. At last follow-up (median 88 months), PRL normalization and tumor disappearance were achieved in 28 and 19.9% of the patients respectively, with no significant sex-related difference observed in CABmax/w or disease control. Mortality was 4.8%, with four patients developing aggressive tumors (4.3%) and three a pituitary carcinoma (3.3%). Conclusion CAB-resistant prolactinomas remain a serious concern. Surgical debulking, newer therapeutic strategies, and early diagnosis of genetic forms could help to improve their outcome.

The endocannabinoid system is critically involved in the regulation of energy balance and represents a potential pharmacotherapeutic target for obesity and type 2 diabetes. New knowledge on the role of this system in humans has been obtained by measuring circulating endocannabinoids in plasma and serum, as well as in cerebrospinal fluid and saliva. Studies over the past few years have in particular provided information on the existing relationship between these biological measurements and the obese phenotype, feeding behavior or responses to body weight loss. Although the functional significance of circulating endocannabinoids has yet to be proven, recent evidence suggests that they might be more than the simple by-product of tissular endocannabinoids spillover. This review outlines recent advances made in determining the potential relevance of circulating endocannabinoids as markers of obesity and metabolic disease.

Context : Neither precise evaluation of pertinent thresholds nor comparison of the diagnostic performance of late-night salivary cortisol (NSC) between inpatient and outpatient settings has been conducted. The usefulness of NSC for the screening of “subclinical” Cushing’s syndrome is still unknown. Objectives : The aim of the study was to compare the influence of inpatient and outpatient settings on the diagnostic performance of NSC and assess its usefulness as a screening test for subclinical Cushing’s syndrome. Design : Consecutive patients were investigated prospectively with two salivary collections, first as inpatients and then as outpatients. Participants: Forty-two obese subjects participated in the study, as well as nine patients cured of Cushing’s disease, 13 with overt Cushing’s syndrome, 14 showing mild recurrence of Cushing’s disease, and 48 with adrenal incidentalomas [23 subclinical cortisol-secreting adenomas (SCSA), 25 nonsecreting adenomas]. Main Outcome Measures : Reproducibility of NSC and diagnostic performance were measured using receiver operating characteristic analysis. Results : NSC in controls was similar between inpatient and outpatient settings. The diagnostic performance of NSC across the different patient groups was similar irrespective of the setting. A threshold of 12 nmol/liter yielded 100% sensitivity and specificity in overt Cushing’s syndrome. Optimal performance in subclinical Cushing’s syndrome required lower thresholds. NSC showed acceptable performance in diagnosing recurrence of Cushing’s disease (90% sensitivity, 91.8% specificity). On the contrary, NSC was similar between patients with SCSA and nonsecreting adenomas. Conclusions : Our data validate the outpatient bed sampling strategy for NSC with no need for specific outpatient threshold. NSC may be helpful to detect mild recurrence of Cushing’s disease after surgery but is of little value in identifying SCSA amongst adrenal incidentalomas.

Background Serum cortisol is routinely quantified by immunoassays. In intensive care units serum free cortisol (FC) determination has been described as a better indicator of survival than total cortisol (TC). To estimate FC different methods are available including saliva sampling. We compared five methods to estimate FC, before and after an ACTH stimulating test in patients suspected of adrenal insufficiency. Method Serum and saliva was collected from 130 patients from the Endocrine Department of a university hospital before and after tetracosactide injection for TC determination. FC was estimated: after serum ultrafiltration, quadratic (Coolens') or cubic (Dorin's) equations, using TC/cortisol-binding globulin concentrations ratio or using cortisol concentration determination in saliva. Results FC concentrations obtained by different techniques were significantly correlated and Passing-Bablok regressions showed no deviation from linearity between salFC and filtFC or quadFC. Using the routine assumption that the patients were correctly diagnosed using a post-tetracosactide TC threshold of 550 nmol/L the FC methods generating the best ROC curves were salFC and filtFC or cubFC 30 min after tetracosactide injection. Conclusions FC concentrations obtained by different techniques are significantly but not similarly correlated with TC. As, salFC and filtFC are more convenient to perform than methods involving CBG assays and are better correlated to TC during tetracosactide tests they may be preferred as FC surrogate assays.

Within the past 15 years, the endocannabinoid system (ECS) has emerged as a lipid signaling system critically involved in the regulation of energy balance, as it exerts a regulatory control on every aspect related to the search, the intake, the metabolism and the storage of calories. An overactive endocannabinoid cannabinoid type 1 (CB1) receptor signaling promotes the development of obesity, insulin resistance and dyslipidemia, representing a valuable pharmacotherapeutic target for obesity and metabolic disorders. However, because of the psychiatric side effects, the first generation of brain-penetrant CB1 receptor blockers developed as antiobesity treatment were removed from the European market in late 2008. Since then, recent studies have identified new mechanisms of action of the ECS in energy balance and metabolism, as well as novel ways of targeting the system that may be efficacious for the treatment of obesity and metabolic disorders. These aspects will be especially highlighted in this review.

OBJECTIVES Obesity with abdominal body fat distribution (A-BFD) and hypothalamic-pituitary-adrenal (HPA) axis activity are somehow linked, but the exact interactions still need clarification. Obese subjects display normal circulating plasma cortisol concentrations with normal circadian rhythms. However, when the HPA axis is pharmacologically challenged, body fat distribution matters and then A-BFD obese women differ from those with subcutaneous body fat distribution (P-BFD). We hypothesized that lower dose provocative and suppressive tests than those used to diagnose hypercortisolism of tumour origin or adrenal insufficiency would shed some light on the characteristics of the HPA axis activity in relation with body fat distribution. PATIENTS AND METHODS Fifty premenopausal obese women were grouped according to their body fat mass distribution. Their plasma cortisol responses to (i) two low doses of dexamethasone (0.25 and 0.5 mg) with (ii) low dose of the ACTH analogue tetracosactrin (1 microg) were assessed. Salivary cortisol was also determined during the ACTH test. RESULTS A-BFD differed from P-BFD women in terms of HPA axis responsiveness. They had comparatively: (i) increased nocturnal cortisol excretion (9.38 +/- 2.2 vs. 6.82 +/- 0.91 nmol/micromol creatinine, A-BFD vs. P-BFD, respectively, P = 0.03); (ii) increased salivary cortisol response to ACTH stimulation (1 microg) [salivary cortisol peak: 33.4 (14.1-129) vs. 28.5 (13.2-42.8) nmol/l; salivary AUC: 825 (235-44738) vs. 537 (69-1420) nmol/min/l; A-BFD vs. P-BFD, P = 0.04 for both]; and (iii) increased pituitary sensitivity to dexamethasone testing [postdexamethasone (0.25 mg) plasma cortisol levels: 163 (26-472) vs. 318 (26-652) nmol/l and postdexamethasone (0.5 mg) plasma cortisol levels: 26 (26-79) vs. 33 (26-402) nmol/l; A-BFD vs. P-BFD, P = 0.01 for both). CONCLUSIONS These data demonstrate differences in the HPA axis activity and sensitivity to glucocorticoids between obese women differing in their body fat distribution, with both enhanced negative and positive feedback in those with abdominal obesity. Several mechanisms may explain these differences: central vs. peripheral hypotheses. Thus, abdominal obesity does not appear to be linked solely to one pathophysiological hypothesis.

To audit the performances of the analytes used in the diagnosis of pheochromocytoma and to present a graphical guideline to help the diagnosis.A 5 year retrospective study.Laboratory and departments of a university hospital.In-patients, suspected of bearing a pheochromocytoma, were investigated for urinary metanephrines and catecholamines (photometric method) and vanillylmandelic acid, fractionated catecholamines and metanephrines [high pressure liquid chromatography (HPLC) coupled to electrochemical detection (ED)] urinary excretion.Patients with a pheochromocytoma (24 out of 2003 patients) were diagnosed by the combination of normetanephrine and metanephrine determination.All analytes but dopamine were significantly elevated in patients with a pheochromocytoma. The area under the receiver operating characteristics (ROC) curves were the highest for total metanephrines, normetanephrine and metanephrine determinations. Because of analytical interferences in the metanephrines determination, the normetanephrine and metanephrine performed better. It is noteworthy that all pheochromocytomas had either normetanephrine or metanephrine levels above their respective optimal threshold (sensitivity 100%). The best optimal threshold performance was reached by the mean of three daily samples. Total or fractionated catecholamines or vanillylmandelic acid were less accurate tools.Amongst urinary tests, the combined use of HPLC/ED determination of normetanephrine and metanephrine seems the most effective screening strategy for the diagnosis of pheochromocytoma. The older total metanephrine photometric assay is grieved by analytical interferences.

ObjectivesWe set up plasma normetanephrine (pNMA) and metanephrine (pMA) assays as they demonstrated their usefulness for diagnosing phaeochromocytomas. Our scope is to describe some practical laboratory aspects and the clinical relevance of these assays in our endocrinological or cardiological departments.MethodsWe retrospectively reviewed the results of MA from a population of in- and outpatients over a 7-year period. Subjects (n=2536) from endocrinological or cardiological departments were investigated (66 phaeochromocytomas). Urinary NMA (uNMA) and pNMA, and urinary MA (uMA) and pMA were assayed by HPLC with electrochemical detection.ResultspNMA and pMA assays are now more frequently requested than uNMA and uMA. This changed our laboratory work load with improved delivery, sensitivity and reliability of plasma assays as well as reduced apparatus maintenance time.The pNMA and pMA upper reference limits (URLs) of subjects with no phaeochromocytoma were 1040 and 430 pmol/l respectively. Sensitivity and specificity based on receiver operating characteristic curves optimal points were 83 and 93% for pNMA at 972 pmol/l and 67 and 98% for pMA at 638 pmol/l. Sensitivity and specificity of paired tests of pMA (positive test: at least one analyte above its URLs) were 100 and 91% respectively.ConclusionThe very low concentration of analytes requires a sustained very good apparatus analytical sensitivity. This can be obtained in an up-to-date laboratory. In terms of clinical performances, assays in plasma or urine are equivalent. Depending on local preferences, populations, strategies or departments, requests for one or the other assay may sustain the need for specifically defined reference ranges.

International audience; BACKGROUND: Erythropoietin (EPO) is an oxygenregulated hormone promoting the differentiation of erythroid progenitor cells. Apart fromhypoxia, few data is available about release by secretagogues including hormones. AIM: To investigate EPO serum concentration in subjects with endocrine diseases. MATERIAL AND METHODS: A retrospective study evaluating serumEPO concentrations in serumleftovers fromsubjects with various endocrine disorders. RESULTS: EPO is not noticeably influenced by thyroid hormone or cortisol concentrations and the relationship with hemoglobin concentration is preserved. In acromegalic patients, the latter is lost but EPO is neither statistically influenced by GH/IGF-I. This may reflect a dual action of GH and/or IGF-I on erythroid progenitors proliferation as well as on EPO synthesis. CONCLUSION: EPO is not noticeably modified by endocrine disorders although GH and or IGF-I may alter EPO relationship with blood hemoglobin concentration.

Contains fulltext : 81945..pdf (Publisher’s version ) (Closed access) OBJECTIVE: Alternative approaches to weight control and physical activity are increasingly needed. Numerous factors influence weight management, including the choice of physical exercise. No study has previously examined the therapeutic effect of a multidisciplinary weight management program incorporating Tai Chi (TC) exercises among sedentary obese women. DESIGN: Randomized intervention trial with blinded medical provider. SETTING: In day hospital consultations. PARTICIPANTS: Twenty-one obese women. INTERVENTION: All subjects participated in a 10-week weight management program that was part of usual care and included a hypocaloric balanced diet, a weekly physician/psychologist/dietician group session, and an exercise program. For the exercise component, subjects were randomized to either a 2-hour weekly session of TC or a conventional structured exercise program. MAIN OUTCOME MEASURES: Changes in weight, body composition, heart rate, blood pressure, mobility scores, mood, Three Factor Eating Questionnaire scores, and General Self-Efficacy. RESULTS: The TC arm improved in resting systolic blood pressure, chair rise test, mood, and reduced percent of fat at week 10 and at 6 months follow-up. General self-efficacy was enhanced in both groups and maintained at 30 weeks. CONCLUSION: The observed benefits over a 30-week period of a multidisciplinary weight management program incorporating TC exercises on physical functioning mood and dietary restraint need further understanding of how sedentary obese women adhere to physical activity like TC or other alternative exercises.

Sex hormones undergo decreases in aging men. Several studies have shown the association of low levels of bioavailable estradiol with osteoporosis in man. To allow a better approach of sex hormones influences, we evaluated bioavailable estradiol concentrations in men and its correlation with age and testosterone. We show that bioavailable estradiol decreases significantly with age. We provide reference values in men with normal testosterone levels.

The diagnostic accuracy of the combined dexamethasone suppression test (DST)-CRH test for the differential diagnosis between Cushing's disease (CD) and pseudo-Cushing syndrome (PCS) has recently been debated.Our objective was to reevaluate the performance of the DST-CRH test to differentiate CD from PCS and compare it with that of midnight plasma cortisol measurement.The study took place at three specialized tertiary care university hospitals.Fourteen patients with PCS and 17 patients with CD matched for 24-h urinary free cortisol were retrospectively studied.Diagnosis or exclusion of CD was the main outcome measure.A 55 nmol/liter cortisol concentration after dexamethasone (DST) yielded 94% sensitivity, 86% specificity, and 90% diagnostic accuracy. Using the historical 38 nmol/liter threshold for plasma cortisol 15 min after CRH administration, the DST-CRH test achieved 100% sensitivity, 50% specificity, and 77% diagnostic accuracy. Increasing the threshold to 110 nmol/liter improved the specificity and diagnostic accuracy to 86 and 93.5%, respectively. However, diagnostic accuracy was not significantly different from that of the DST. A midnight plasma cortisol concentration of more than 256 nmol/liter was consistent with the diagnosis of CD with 100% sensitivity, specificity, and diagnostic accuracy.The diagnostic performance of the DST-CRH test for the differential diagnosis between PCS and mild CD was lower than previously reported. Although the specificity of the test is improved using a revised cortisol threshold, its diagnostic accuracy is not better than that of the standard DST. Our study supports the preferential use of the DST and midnight plasma cortisol measurement as first-line diagnostic tests in equivocal cases.

The pituitary origin of ACTH secretion in ACTH-dependent hypercortisolism can be difficult to assess, as magnetic resonance imaging (MRI) frequently fails to identify ACTH-secreting microadenomas or, on the contrary, may give false positive images of microadenomas. The choice of therapeutic option for patients with such normal MRI findings is controversial. Some groups propose routinely pituitary surgery, whereas others consider that neurosurgical exploration may be less successful and more harmful, and therefore prefer other types of management. The aim of this study was to compare surgical outcomes between patients with Cushing's disease (CD) and normal vs. positive pituitary MRI findings. Fifty-four patients (44 women and 10 men) with CD, operated on after 1996 in two centers (Kremlin-Bicetre and Bordeaux) and followed postoperatively during a mean period of 19.9 +/- 22.7 months (range, 1-89 months), were enrolled in this retrospective study. Twenty-eight patients had normal pituitary MRI findings, and the pituitary origin of ACTH was established by bilateral petrosal sinus sampling in all of these cases. Twenty-six patients had positive MRI findings clearly showing a microadenoma. The two groups were not significantly different in terms of the sex ratio, age, frequency of hypertension, or diabetes, basal 24-h urinary free cortisol levels and follow-up. All of the patients were operated on by two experienced neurosurgeons using the same surgical protocol. Selective adenomectomy was performed when a tumor was identified, and subtotal hypophysectomy was performed when the lesion was uncertain or when no tumor was found during surgical exploration. Respectively, 50% and 84% of patients with normal and positive MRI results underwent adenomectomy (P < 0.05). A pituitary adenoma (confirmed by pathological examination) was found at surgery in 53% and 88% of patients in the normal and positive MRI groups, respectively (P < 0.05). The early surgical success rate (combining patients with corticotropic deficiency and patients with eucortisolism) was similar in the normal and positive MRI groups (78% and 88%, respectively; P = 0.85). The recurrence rate was lower in the normal MRI group, but the difference did not reach statistical significance (9% vs. 30%; P = 0.07). The final remission rate at the last visit was similar in the normal and positive MRI groups (72% and 61%, respectively; P = 0.29). Postoperative complications were also similar: 10 patients (36%) with normal MRI and five patients (20%) with positive MRI had at least one postoperative complication (surgical and/or pituitary deficiency; P = 0.12). Thus, the outcome of pituitary surgery in CD appears to be similar regardless of whether pituitary MRI shows a microadenoma. We recommend neurosurgical pituitary exploration as the first-line treatment of CD, provided that the pituitary origin of ACTH secretion is confirmed by bilateral petrosal sinus sampling in patients with normal pituitary MRI findings.