The value of a multidisciplinary consensus meeting in achieving agreement on eating disorders diagnosis at a specialized referral center.

OBJECTIVE: This study aimed to evaluate the concordance of eating disorders (EDs) diagnoses within a multidisciplinary team in a specialized hospital unit dedicated to the medical care of ED. METHODS: The study analyzed data from 608 female patients who sought consultation at the Eating Disorders Referral Center between 2017 and 2021. The diagnoses were established according to the DSM-5 criteria by endocrinologists, psychiatrists, and finally confirmed or discussed within a monthly multidisciplinary consensus meeting (MCM). Fleiss' Kappa tests were conducted to assess inter-raters' agreement. RESULTS: Overall, substantial agreement was observed between endocrinologists and psychiatrists and the MCM. A more detailed analysis revealed variations in agreement across different disorders. Certain EDs demonstrated substantial agreement (e.g., anorexia nervosa restrictive subtype), while others approached near-perfect agreement (e.g., binge-eating disorder). In contrast, agreement was fair to poor for anorexia nervosa binge-purge subtype (ANBP) and slight for other specified feeding and ED. A period of temporary disagreement was noted for ANBP, partially attributed to practitioner turnover. An improvement in interdisciplinary agreement was observed for all ED diagnoses by the end of the study period. DISCUSSION: Variations or lower levels of inter-rater agreement may stem from atypical cases that fall on the border between two diagnoses or complex cases, as well as fluctuating symptoms. The progress observed throughout the study can be attributed in part to interdisciplinary learning, particularly facilitated by the MCM. The findings underscore the significance of striving for optimal concordance among different medical specialties to enhance patient care in ED treatment. PUBLIC SIGNIFICANCE: This study scrutinizes the agreement levels of ED diagnoses among endocrinologists and psychiatrists within a multidisciplinary team at an Eating Disorders Referral Center. While substantial overall agreement was achieved, disparities or lower agreement levels were evident for certain diagnoses such as anorexia nervosa binge-purge subtype. However, collaborative meetings led to a progressive enhancement in agreement over time. This research underscores the crucial role of a multidisciplinary team working collectively to ensure precise diagnoses and improved care for patients with EDs.

Circadian copeptin and oxytocin profiles in anorexia nervosa: Exploring the interplay with neurohypophysis opioid tone.

CONTEXT: Neurohypophysis (NH) function in eating disorders (ED) remains poorly elucidated. Studies on vasopressin and oxytocin display inconclusive findings regarding their levels and associations with psychological complications in ED. The profile of opioid tone, a crucial NH activity regulator, is also unknown. OBJECTIVE: To characterise the circadian profile of NH hormones and NH opioid tone using positron emission tomography/MRI (PET/MRI) imaging in patients with ED compared to healthy controls. METHODS: Twelve-point plasma circadian profiles of copeptin and oxytocin, alongside nutritional and psychological scores, were assessed in age-matched female participants: 13 patients with anorexia nervosa restrictive-type (ANR), 12 patients recovered from AN (ANrec), 14 patients with bulimia nervosa and 12 controls. Neurohypophysis PET/MRI [11C] diprenorphin binding potential (BPND) was evaluated in AN, ANrec and controls. RESULTS: Results revealed lower copeptin circadian levels in both ANR and ANrec compared to controls, with no oxytocin differences. Bulimia nervosa exhibited elevated copeptin and low oxytocin levels. [11C] diprenorphin pituitary binding was fully localised in NH. Anorexia nervosa restrictive-type displayed lower NH [11C] diprenorphin BPND (indicating higher opioid tone) and volume than controls. In ANR, copeptin inversely correlated with osmolarity. Neurohypophysis [11C] diprenorphin BPND did not correlated with copeptin or oxytocin. CONCLUSION: Copeptin demonstrated significant group differences, highlighting its potential diagnostic and prognostic value. Oxytocin levels exhibited conflicting results, questioning the reliability of peripheral blood assessment. Increased NH opioid tone in anorexia nervosa may influence the vasopressin or oxytocin release, suggesting potential therapeutic applications.

Association of gut-specific non-inflammatory T lymphocytes with chronic anorexia nervosa and constitutional thinness.

OBJECTIVE: Previous studies of AN showed low-grade inflammation. Are low-grade inflammation and circulating lymphocytes associated with chronic conditions? METHOD: Peripheric blood cytokines were measured using Luminex™ technology in a chronic AN cohort (mean = 67.42 months), compared to Constitutional Thinness (CT), Constitutional Obesity (CO), and Healthy Controls (HC). Secondarily a prospective cohort of chronic AN (mean = 54.11 months) was recruited to compare the functional lymphocyte profile in blood by flow cytometry to CT and HC. RESULTS: In the AN group, most cytokine concentrations were lower than in CT and HC groups. The IL-23 (98.02 pg/ml) was elevated related to HC and CO, and the IL-10 (4.178 pg/ml) was elevated versus CO. In the CT group, IL-9 (0.06216 pg/ml) was elevated compared to AN. The AN group had high Treg (9.259% of CD4+ ) and CD8+ Integrinß7+ (9.552% of CD3+ ) versus HC for lymphocyte populations. In CT group, elevated Treg (9.7% of CD4+ ) elevated percentage of CD4+ CCR9+ (5.867% of CD3+ ) and CD8+ Integrinß7+ (10.21% of CD3+ ) were found versus HC. CONCLUSIONS: The chronic state of AN and CT is surprisingly non-inflammatory with elevated Treg cells. These results suggest that maintaining a dysregulated response to intestinal antigens may contribute to maintaining AN.

Continuous glucose monitoring assessment in patients suffering from anorexia nervosa reveals chronic prolonged mild hypoglycemia all over the nycthemeron.

OBJECTIVE: Anorexia nervosa (AN) is an eating disorder characterised by voluntary dietary restriction leading to severe undernutrition. Hypoglycaemia is mostly described through severe case reports and is always evaluated by fasting or post-meal blood glucose, showing nothing about hypoglycaemia's length or duration. The interest of continuous interstitial glucose monitoring (CGM), largely used in diabetes mellitus, has never been evaluated in AN patients. METHOD: Glycaemia cycles in AN patients were assessed using CGM over 5 days and then analysed according to food intake. RESULTS: Mean glycaemia was within normal range. 91% of the patients presented with at least one episode with glycaemia under 70 mg/dl. Within the 24 h, the percentage of time spent with a glycaemia under 70 mg/dl was of 20.82 ± 3.90% with a maximum of 52%. We found 2.52 ± 0.33 hypoglycaemia events per 24 h, including 21.11 ± 3.76% at night. CGM parameters correlated with cortisol and IGF1 plasma levels. Comparison with estimated carbohydrate intakes discriminated concordant and non-concordant estimations depending on patient. CONCLUSIONS: AN patients display chronic prolonged mild hypoglycaemia all over the nycthemeron despite normal fasting glycaemia. Associated adaptive increased counter-regulatory hormones might protect AN patients from deeper hypoglycaemia. CGM allowed testing food intake self-estimation reliability of AN patients and could be a very useful biofeedback tool.

Is constitutional thinness really different from anorexia nervosa? A systematic review and meta-analysis.

A growing interest in constitutional thinness has been observed in the last decades, but the publications however cover various fields of study and report equivocal results. The present work systematically reviewed any clinical trials enrolling participants with constitutional thinness and bibliographic researches were performed between December 2018 and June 2020. From a total of 1 212 records initially identified, 402 records were removed as duplicates, 381 articles were excluded based on titles or abstracts and 390 references were excluded against eligibility criteria. Thirty-nine articles were finally included in the systematic review. The results showed that constitutionally thin people seem to be underweight but not underfat and present a fat-free mass as blunted as anorexic patients, despite being a little less underweight. The meta-analysis confirmed that constitutionally thin people present normal energy intake and revealed a trend toward a higher resting metabolic rate to fat-free mass ratio which suggests a highly metabolic fat-free mass. Contrary to patients with anorexia nervosa, constitutionally thin people present normal levels of insulin-like growth factor 1, estradiol, growth hormone, follicle-stimulating hormone, and luteinizing hormone. An intermediate level of leptin between anorexic and control participants was however observed in constitutional thinness. While all the studies reported normal free triiodothyronine and cortisol levels in constitutionally thin individuals, a higher fasting free triiodothyronine level (p = 0.033) and a lower 24 h mean cortisol level (p = 0.005) were observed for the first time. Present results give robust evidence that constitutionally thin people present an atypical phenotype highly different from anorexia nervosa.

Relationship between obesity and severe COVID-19 outcomes in patients with type 2 diabetes: Results from the CORONADO study.

AIM: To assess the relationship between body mass index (BMI) classes and early COVID-19 prognosis in inpatients with type 2 diabetes (T2D). METHODS: From the CORONAvirus-SARS-CoV-2 and Diabetes Outcomes (CORONADO) study, we conducted an analysis in patients with T2D categorized by four BMI subgroups according to the World Health Organization classification. Clinical characteristics and COVID-19-related outcomes (i.e. intubation for mechanical ventilation [IMV], death and discharge by day 7 [D7]) were analysed according to BMI status. RESULTS: Among 1965 patients with T2D, 434 (22.1%) normal weight (18.5-24.9 kg/m2 , reference group), 726 (36.9%) overweight (25-29.9 kg/m2 ) and 805 (41.0%) obese subjects were analysed, including 491 (25.0%) with class I obesity (30-34.9 kg/m2 ) and 314 (16.0%) with class II/III obesity (≥35 kg/m2 ). In a multivariable-adjusted model, the primary outcome (i.e. IMV and/or death by D7) was significantly associated with overweight (OR 1.65 [1.05-2.59]), class I (OR 1.93 [1.19-3.14]) and class II/III obesity (OR 1.98 [1.11-3.52]). After multivariable adjustment, primary outcome by D7 was significantly associated with obesity in patients aged younger than 75 years, while such an association was no longer found in those aged older than 75 years. CONCLUSIONS: Overweight and obesity are associated with poor early prognosis in patients with T2D hospitalized for COVID-19. Importantly, the deleterious impact of obesity on COVID-19 prognosis was no longer observed in the elderly, highlighting the need for specific management in this population.

Use of dipeptidyl peptidase-4 inhibitors and prognosis of COVID-19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study.

AIM: To investigate the association between routine use of dipeptidyl peptidase-4 (DPP-4) inhibitors and the severity of coronavirus disease 2019 (COVID-19) infection in patient with type 2 diabetes in a large multicentric study. MATERIALS AND METHODS: This study was a secondary analysis of the CORONADO study on 2449 patients with type 2 diabetes (T2D) hospitalized for COVID-19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP-4 inhibitors users vs. non-users) and were used in multivariable logistic regression models to estimate the average treatment effect in the treated as inverse probability of treatment weighting (IPTW). RESULTS: Five hundred and ninety-six participants were under DPP-4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non-users of DPP-4 inhibitors (27.7% vs. 28.6%; p = .68). In propensity analysis, the IPTW-adjusted models showed no significant association between the use of DPP-4 inhibitors and the primary outcome by Day 7 (OR [95% CI]: 0.95 [0.77-1.17]) or Day 28 (OR [95% CI]: 0.96 [0.78-1.17]). Similar neutral findings were found between use of DPP-4 inhibitors and the risk of tracheal intubation and death. CONCLUSIONS: These data support the safety of DPP-4 inhibitors for diabetes management during the COVID-19 pandemic and they should not be discontinued.

Two new reliable immunohistochemical methods for simultaneous identification of capillaries, the three types of fibers and basal lamina in human skeletal muscle.

Capillary network of skeletal muscle has a crucial role in oxygen supply and is strongly associated with the phenotype and metabolic profile of muscle fibers. Abundant literature has explored capillarization of skeletal muscle in different populations and in response to different interventions. Capillary and fiber type identification techniques have considerably evolved over the last decades, but to the best of our knowledge, no validated immunohistochemical method has yet been developed to simultaneously identify capillaries (using CD31), the three different muscle fiber types, and basal lamina. Nine human muscle biopsies of vastus lateralis were stained using 5 different methods to test: the reliability of different CD31 antibodies for capillary identification, the reliability between single-section or serial-section methods, and the intra-experimenter reproducibility in visual detection of capillaries. High reliability for the different antibodies directed against capillaries was observed for capillary contacts (CC) measurements (intra-class correlations (ICC) [ICC95%] of 0.89 [0.72; 0.96] for type I fibers, 0.93 [0.81; 0.97] for type IIA fibers, 0.88 [0.71; 0.96] for type IIX fibers, 0.95 [0.86; 0.98] for all fiber types) as well as a high level of similarity between single and serial sections methods. A strong similarity in capillary analysis between the different methods was obtained for each sample measurements. Analysis of Lin's concordance correlation coefficients and Bland and Altman's graphics showed a strong intra-experimenter reproducibility. This article proposes two time- and tissue-sparing immunohistochemical methods to accurately assess a complete fiber typing (type I, IIA, and IIX) along with muscle capillarization on a single muscle section.

Definition and diagnosis of constitutional thinness: a systematic review.

The existing literature about the definition and diagnostic criteria of constitutional thinness (CT) appears equivocal. The present work systematically reviewed the criteria used in the diagnosis of adult individuals with CT (PROSPERO registration number: CRD42019138236). Five electronic bibliographic databases were searched between December 2018 and November 2019: MEDLINE, Embase, CENTRAL (Cochrane Library), Google Scholar and Clinical Trials. Search terms were combined with Medical Subject Headings terms. The search strategy included any clinical trials that enrolled adults with CT. Studies were systematically excluded if the state of thinness was not due to a well-identified constitutional origin. From the 689 references after duplicate removal, 199 studies were excluded based on title and 164 based on abstract. According to the inclusion and exclusion criteria, 291 other studies were removed. Finally, thirty-five studies remained at the end of the process. The analysis of these studies showed high heterogeneity in the diagnostic criteria of CT. A real need emerged to adopt a common terminology and to systematically exclude potential non-constitutional origins of thinness such as eating disorders, associated pathology or over-exercising, with validated tools. Weight history, physiological menses and weight gain resistance are also important criteria to consider. The present systematic review revealed that our medical and scientific approaches of CT need to be harmonised in terms of terminology and diagnostic criteria. Although further studies are needed, we finally proposed recommendations and a decision tree to help in the recognition and diagnosis of CT.

Ghrelin acylation by ghrelin- O-acyltransferase can occur in healthy part of oncological liver in humans.

Activation of ghrelin is controlled by the enzyme ghrelin- O-acyl transferase (GOAT). In humans, localization of this acylation is poorly understood. The aim of this study is to explore GOAT localization and activation in the human liver by evaluating both bioactive and non-bioactive ghrelin in the bloodstream entering and leaving the liver and to simultaneously evaluate GOAT mRNA expression in the liver. A healthy part of oncologic hepatic tissue collected from nine patients undergoing hepatectomy was used to evaluate GOAT mRNA expression by quantitative real-time polymerase chain reaction (RT-qPCR). Simultaneously, blood from the portal vein, the suprahepatic vein, the subclavicular vein, and the radial artery was also sampled to assay total and acylated ghrelin. Acylated ghrelin level was significantly increased in the suprahepatic vein compared with the portal vein level (385 ± 42 ng/ml vs. 268 ± 24 ng/ml, P = 0.04). Suprahepatic-to-portal vein ratio for acylated ghrelin (acylation ratio) is 1.4 ± 0.1. Mean expression of GOAT mRNA in the liver, expressed as 2-∆Ct·µg total RNA-1·1 µl of liver tissue-1 was at 0.042 ± 0.021 arbitrary units. GOAT mRNA expression in the liver was correlated with acylated-to-total ghrelin ratio in the suprahepatic vein ( P = 0.016, R = 0.75) and with the acylation liver ratio ( P = 0.05, R = 0.61). Blood concentration of acylated ghrelin was found significantly increased after its passage through the liver, suggesting that acylation can occur in the liver. RT-qPCR data confirmed the presence of GOAT in the liver, with a positive correlation between GOAT expression and acylated ghrelin liver ratio. This study strongly suggests that the liver is a site of ghrelin acylation in humans. NEW & NOTEWORTHY Although the activation of ghrelin by the enzyme ghrelin- O-acyl transferase (GOAT) is yet well demonstrated, its localization, especially in humans, remains poorly understood. We explored GOAT localization and activation in the human liver by simultaneously evaluating both bioactive and non-bioactive ghrelin in the bloodstream entering and leaving the liver and also GOAT mRNA expression in the liver. We therefore showed for the first time, to our knowledge, that GOAT localized in the liver is active and takes part in ghrelin activation.

Structure-function relationship of the pituitary gland in anorexia nervosa and intense physical activity.

Patients with Anorexia Nervosa (AN) and athletes share intense physical activity and pituitary hormonal disturbances related to absolute (AN) or relative (athletes) undernutrition. Pituitary gland (PG) structure evaluations in those conditions are scarce, and did not differentiate anterior from posterior lobe. We evaluated the structure-function relationship of anterior and posterior PG in AN and athletes, and potential reversibility of this alteration in a group of weight-recovered patients (AN_Rec). Manual delineation of anterior (AP) and posterior (PP) PG was performed on T1-weighted MR images in 17 women with AN, 15 women with AN_Rec, 18 athletes women and 25 female controls. Anthropometric, hormonal, and psychometric parameters were explored and correlated with PG volumes. AP volume (APV) was lower in AN (448 ± 82 mm3), AN_Rec (505 ± 59 mm3), and athletes (540 ± 101 mm3) vs. Controls (615 ± 61 mm3, p < 0.00001, p < 0.00001 and p = 0.02, respectively); and smaller in AN vs. AN_Rec (p = 0.007). PP volume did not show any differences between the groups. APV was positively correlated with weight (R = 0.36, p = 0.011) in AN, and luteinizing hormone (R = 0.35, p = 0.014) in total group. In AN, mean growth hormone (GH) was negatively correlated with global pituitary volume (R = 0.31, p = 0.031) and APV (R = 0.29, p = 0.037). Absolute and relative undernutrition led to a decreased anterior pituitary gland volume, which was reversible with weight gain, correlated with low bodyweight, and blockade of gonadal hypothalamic-pituitary axis. Intriguing inverse correlation between anterior pituitary gland volume and GH plasma level could suggests a low storage capacity of anterior pituitary gland and increased reactivity to low insulin-like growth factor type 1.

Older adult women with chronic anorexia nervosa: heterogeneous adaptation to undernutrition over time.

INTRODUCTION: Anorexia nervosa (AN) in older adult women is primarily described through reviews or case reports focusing on psychiatric traits, with no comprehensive studies evaluating their complete nutritional and hormonal profiles. This study aimed to describe a group of women with anorexia nervosa aged above 35 years old (AN35), and compare them with young women with anorexia nervosa (ANY) and normal-weight control participants. METHOD: Anthropometric, metabolic, nutritional, and psychiatric parameters were collected and compared among three groups of women: 50 AN35, 37 ANY, and 38 controls. RESULTS: AN35 exhibited a mean disease duration of 271 ± 19 months, with 94% chronic forms and 58% restrictive types. Despite having similar BMI as ANY, AN35 displayed more altered parameters, including higher liver enzymes (p = 0.007), free T3 (p = 0.0046) and leptin (p < 0.0001); and lower albumin (p = 0.0029), and white cells (p < 0.0001). AN35 showed significant heterogeneity in hormonal adaptation, such as free T3. Half of the patients aged above 51 years revealed high gonadotropin levels despite being undernourished. Additionally, AN35 groups presented with 50% of bones fractures, decreased T-scores under -2.5 (p < 0.0001 for femoral), and altered micro architectural HRPQT parameters compared to ANY. CONCLUSION: Anorexia nervosa in older adult women is predominantly chronic. Nutritional parameters changes with age suggests a significant heterogeneity and possible adaptation of energy balance and bodyweight set point for others. Complications may be severe, altering the quality of life, and sometimes potentially lethal. These findings highlight the potential adaptation of energy balance with age, and should assist clinicians in clinical practice.

MRI atlas of the pituitary gland in young female adults.

The probabilistic topography and inter-individual variability of the pituitary gland (PG) remain undetermined. The absence of a standardized reference atlas hinders research on PG volumetrics. In this study, we aimed at creating maximum probability maps for the anterior and posterior PG in young female adults. We manually delineated the anterior and posterior parts of the pituitary glands in 26 healthy subjects using high-resolution MRI T1 images. A three-step procedure and a cost function-masking approach were employed to optimize spatial normalization for the PG. We generated probabilistic atlases and maximum probability maps, which were subsequently coregistered back to the subjects' space and compared to manual delineations. Manual measurements led to a total pituitary volume of 705 ± 88 mm³, with the anterior and posterior volumes measuring 614 ± 82 mm³ and 91 ± 20 mm³, respectively. The mean relative volume difference between manual and atlas-based estimations was 1.3%. The global pituitary atlas exhibited an 80% (± 9%) overlap for the DICE index and 67% (± 11%) for the Jaccard index. Similarly, these values were 77% (± 13%) and 64% (± 14%) for the anterior pituitary atlas and 62% (± 21%) and 47% (± 17%) for the posterior PG atlas, respectively. We observed a substantial concordance and a significant correlation between the volume estimations of the manual and atlas-based methods for the global pituitary and anterior volumes. The maximum probability maps of the anterior and posterior PG lay the groundwork for automatic atlas-based segmentation methods and the standardized analysis of large PG datasets.

Systematic review of prospective studies assessing risk factors to predict anorexia nervosa onset.

BACKGROUND: According to case‒control studies, a multitude of factors contribute to the emergence of anorexia nervosa (AN). The present systematic review examines prospective studies specifically designed to evaluate the prediction of AN onset. METHODS: According to the ARMSTAR 2 and PRISMA 2020 checklists, the PubMed, PsycINFO and Cochrane databases were searched. The methodological quality of the studies was assessed with the Downs and Black checklist. RESULTS: Three articles concerning prospective studies of the general population were ultimately included in the review. The methodological quality of these studies was not optimal. Bidirectional amplification effects were observed between risk factors, some of which could have a relative predictive force as low bodyweight or body dissatisfaction. Even if not included according to specified criteria for this systematic review 11 longitudinal studies, with retrospective analysis of AN onset' prediction, were also discussed. None of these studies asserted the predictive value of particular risk factors as low body weight, anxiety disorders or childhood aggression. CONCLUSIONS: To date there are insufficient established data to propose predictive markers of AN onset for predictive actions in pre-adolescent or adolescent populations. Future work should further evaluate potential risk factors previously identified in case‒control/retrospective studies within larger prospective investigations in preadolescent populations. It is important to clearly distinguish predisposing factors from precipitating factors in subjects at risk of developing AN.

Currently health care guidelines for eating disorders do not include proposal of markers to predict the onset of anorexia nervosa. The current work provides a systematic review of the scientific literature concerning this subject. To date only three published studies were designed in a prospective longitudinal way to evaluate potential predictors of anorexia nervosa onset. When taking into account these studies only low bodyweight and body dissatisfaction in early puberty were proposed as predicting elements for further anorexia nervosa development. Meanwhile the prediction precision was calculated for none of them. No other psychological elements were retained or studied. The age range of the population entering the follow up in these studies was too large covering the peak age of anorexia nervosa itself (13­16 years of age). Larger prospective studies including prepubescent individual and evaluating more psychological markers (perfectionism, negative affectivity or negative self-evaluation) or environmental ones are needed.

Mechanisms and predictors of menses resumption once normal weight is reached in anorexia nervosa.

BACKGROUND: In cases of Anorexia Nervosa (AN), achieving weight gain recovery beyond the lower limits set by the World Health Organization and normalizing classical nutritional markers appears to be essential for most patients. However, this is not always adequate to restore menstrual cycles. This discrepancy can cause concern for both patients and healthcare providers, and can impact the medical management of these individuals. Thus, the purpose of this study was to assess the ability of anthropometric and hormonal factors to predict the resumption of menstrual cycles in individuals with anorexia nervosa upon reaching a normal body weight. METHOD: Patients with AN who had achieved a normal Body Mass Index but had not yet resumed their menstrual cycles (referred to as ANRec) were evaluated on two occasions: first at visit 1 and then again 6 months later, provided their body weight remained stable over this period (visit 2). Among the 46 ANRec patients who reached visit 2, they were categorized into two groups: 20 with persistent amenorrhea (PA-ANRec) and 26 who had regained their menstrual cycles (RM-ANRec). Anthropometric measurements, several hormone levels, Luteinizing Hormone (LH) pulsatility over a 4-h period, and LH response to gonadotropin-releasing hormone injection (LH/GnRH) were then compared between the two groups at visit 1. RESULTS: Patients in the RM-ANRec group exhibited higher levels of follicular stimulating hormone, estradiol, inhibin B, LH/GnRH, and lower levels of ghrelin compared to those in the PA-ANRec group. Analysis of Receiver Operating Characteristic curves indicated that having ≥ 2 LH pulses over a 4-h period, LH/GnRH levels ≥ 33 IU/l, and inhibin B levels > 63 pg/ml predicted the resumption of menstrual cycles with a high degree of specificity (87%, 100%, and 100%, respectively) and sensitivity (82%, 80%, and 79%, respectively). CONCLUSIONS: These three hormonal tests, of which two are straightforward to perform, demonstrated a high predictive accuracy for the resumption of menstrual cycles. They could offer valuable support for the management of individuals with AN upon achieving normalized weight. Negative results from these tests could assist clinicians and patients in maintaining their efforts to attain individualized metabolic targets. TRIAL REGISTRATION: IORG0004981.

Once a minimally normal weight has been reached during eating disorder recovery for female patients with anorexia nervosa (AN), the persistence of amenorrhea can be a cause for concern both patient and practitioner. In our study, we have discovered that positive results in biological blood tests, which can be conveniently conducted in an ambulatory setting, offer valuable predictive insights. Specifically, parameters such as LH pulse numbers exceeding 2, LH response to GnRH injection surpassing 33 UI/L, or Inhibin B levels in the blood exceeding 63 pg/mL, can accurately predict the resumption of menstrual cycles in the upcoming months, provided that the patient does not experience weight loss or engage in intense exercise. Conversely, negative results from these tests at this critical juncture in the recovery process can serve as valuable tools to encourage and motivate both the healthcare provider and the patient. By maintaining their efforts and continuing to increase their weight, patients can work towards a more comprehensive restoration of their menstrual cycles.

Normal inhibin B levels suggest partial preservation of gonadal function in adult male patients with anorexia nervosa.

INTRODUCTION: The impact of undernutrition on endocrine and exocrine gonadatrope function is poorly known in male anorexia nervosa (AN) patients. AIM: The aim of this study was to compare the pituitary-gonadal function of male AN subjects with that of healthy controls, Kallmann syndrome (KS) patients, and female AN subjects. METHODS: Observational monocentric cross-sectional study performed in 31 male and 25 female subjects with restrictive-type AN, 22 male and 20 female controls, and nine male KS patients. MAIN OUTCOME MEASURES: Hormonal parameters are as follows: follicule stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, estradiol, testosterone, inhibin B, thyroid hormones, growth hormone (GH), insulin-like growth factor 1 (IGF-1), cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, and leptin. RESULTS: Similar abnormalities of free T3, GH, IGF-I, cortisol, and leptin were found in men as in AN women with equivalent undernutrition status when compared with corresponding controls. Low levels of LH, FSH were found in both male and female AN patients. In male AN, total testosterone was found lower than in controls but higher than in KS, while a lack of estradiol was noticed in AN women. Sex hormones variations were directly related to weight gain only in AN men. No relationship was found between sex hormones and leptin variation for both sexes. In AN men, inhibin B levels were similar to that of controls and did not correlate with testosterone levels. CONCLUSIONS: Significant differences of undernutrition impact on gonadal status were noticed between male and female AN subjects, including partial preservation of testosterone release and probable preservation of exocrine function, according to the normal inhibin B levels.

Performance of quantitative measurements in [18F]fluorocholine positron emission tomography/computed tomography for parathyroid imaging (P2TH study).

Objective: [18F]Fluorocholine positron emission tomography/computed tomography (PET/CT) is used frequently in addition to [99mTc]Tc-Sestamibi scintigraphy and ultrasonography for the location of hyperfunctioning parathyroid glands. The aim of this study is to evaluate the performance of quantitative criteria in [18F]fluorocholine PET/CT for localization of hyperfunctioning parathyroid glands. The secondary objective is to highlight a correlation between the detection rate of [18F]fluorocholine PET/CT and serum parathyroid hormone (PTH) level. Materials and methods: In two academic centers, we retrospectively included patients with biological hyperparathyroidism (HPT) and who had [18F]fluorocholine PET/CT. After a visual analysis, to measure the overall performance of [18F]fluorocholine PET/CT, a blind reading was carried out with standardized measurements of maximum standardized uptake value (SUVmax), liver ratio, thyroid ratio, and size ratio. We analyzed the quantitative criteria of [18F]fluorocholine PET/CT compared to the histological results, in particular to identify differences between adenomas and hyperplasias. We compared the performance of each quantitative criterion to the overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F]fluorocholine PET/CT. The detection rate of hyperfunctioning parathyroid glands was calculated in subgroups of serum PTH level. Results: The quantitative criteria in [18F]fluorocholine PET/CT were measured for 120 patients (135 lesions). The areas under the receiver operating characteristic (ROC) curve representing SUVmax and liver ratio were significantly increased. The optimal cut-off values represented by the maximum Youden index was >4.12 for SUVmax and >27.4 for liver ratio. Beyond certain threshold values of SUVmax (>4.12) or liver ratio (>38.1), all the lesions were histologically proven adenomas. SUVmax and liver ratio were significantly higher for adenomas than for hyperplasias and differential diagnosis (p = 0.0085 and p = 0.0002). The positivity of [18F]fluorocholine PET/CT was correlated with PTH level. Detection rates were 55.56, 75.56, and 87.5%, respectively, for serum PTH < 70, 70 to 120, and >120 ng/ml. Conclusion: Semi-quantitative measurements (SUVmax and liver ratio) should be considered as additional tools in interpretation of [18F]fluorocholine PET/CT. These quantitative parameters have lower overall performance but higher specificity than overall visual analysis in identifying an adenoma. Above certain threshold values, all lesions are adenomas. [18F]fluorocholine PET/CT confirms excellent performance for the detection of hyperfunctional parathyroids. For serum PTH levels < 70 ng/ml, the detection rate of [18F]fluorocholine PET/CT is strongly decreased.

Proteomics reveals unique plasma signatures in constitutional thinness.

PURPOSE: Studying the plasma proteome of control versus constitutionally thin (CT) individuals, exposed to overfeeding, may give insights into weight-gain management, providing relevant information to the clinical entity of weight-gain resistant CT, and discovering new markers for the condition. EXPERIMENTAL DESIGN: Untargeted protein relative quantification of 63 CT and normal-weight individuals was obtained in blood plasma at baseline, during and after an overfeeding challenge using mass spectrometry-based proteomics. RESULTS: The plasma proteome of CT subjects presented limited specificity with respect to controls at baseline. Yet, CT showed lower levels of inflammatory C-reactive protein and larger levels of protective insulin-like growth factor-binding protein 2. Differences were more marked during and after overfeeding. CT plasma proteome showed larger magnitude and significance in response, suggesting enhanced "resilience" and more rapid adaptation to changes. Four proteins behaved similarly between CT and controls, while five were regulated in opposite fashion. Ten proteins were differential during overfeeding in CT only (including increased fatty acid-binding protein and glyceraldehyde-3-phosphate dehydrogenase, and decreased apolipoprotein C-II and transferrin receptor protein 1). CONCLUSIONS AND CLINICAL RELEVANCE: This first proteomic profiling of a CT cohort reveals different plasma proteomes between CT subjects and controls in a longitudinal clinical trial. Our molecular observations further support that the resistance to weight gain in CT subjects appears predominantly biological. CLINICALTRIALS: gov Identifier: NCT02004821.

New Insights on Bone Tissue and Structural Muscle-Bone Unit in Constitutional Thinness.

While few studies pointed out low bone mineral densities in constitutionally thin women, little is known about potential explanations. The objective was to further explore bone architecture in both women and men with constitutional thinness to investigate their mechanical muscle-bone coupling (or uncoupling). Thirty constitutionally thin people and 31 normal weight controls participated in the study. Body composition, hip structural analysis, and trabecular bone score were assessed by dual-energy X-ray absorptiometry, bone architecture using high-resolution peripheral quantitative computed tomography, and muscle explorations through histological staining on muscle biopsies. Thirty-two out of the 48 indexes relative to density, geometry, texture, and architecture of bones were found significantly lower (p < 0.05) in constitutionally thin individuals compared with controls. This observation was particularly pronounced in constitutionally thin men. Bone microarchitecture was more altered in weight-supporting bone (tibia) than in non-weight-supporting (radius) bone, which might refer to a normal physiological adaptation (Frost's mechanostat theory). Yet, the heat-maps of correlations analyses showed many alterations of body weight or muscle associations with bone parameters in constitutionally thin individuals contrary to controls. Present results might support the idea of intrinsic disturbances of bone cells independently to the small muscle structure, particularly in men.