Francois Lang

Ghrelin/obestatin ratio in two populations with low bodyweight: Constitutional thinness and anorexia nervosa

Constitutional thinness (CT) and anorexia nervosa (AN) are two categories of severely underweight subjects. Some appetite-regulating hormones display opposite levels in AN and CT. While levels of ghrelin, an orexigenic hormone, fit with the normal food intake in CT, the lack of efficacy of increased ghrelin levels in AN is not clear. Obestatin is a recently described peptide derived from the preproghrelin gene, reported to inhibit appetite in contrast to ghrelin. The aim of this study was to determine whether the circadian profile of obestatin, total and acylated ghrelin levels is different in CT subjects when compared with AN patients. Six-points circadian profiles of plasma obestatin, acylated ghrelin, total ghrelin and other hormonal and nutritional parameters were evaluated in four groups of young women: 10 CT, 15 restricting-type AN, 7 restored from AN and 9 control subjects. Obestatin circadian levels were significantly higher in AN (p<0.0001) while no difference was found between CT and control subjects. Acylated and total ghrelin were found increased in AN. Acylated ghrelin/obestatin and total ghrelin/obestatin were found decreased in AN compared to CT or C subjects (p<0.05). The percentage of acylated ghrelin was found decreased in CT group (p<0.05). The decreased ghrelin/obestatin ratio found in AN might participate in the restraint in nutriment intake of these patients. In contrast, in CT a lower percentage of acylated over total ghrelin might be considered in the aetiology of this condition.

Hormonal Profile Heterogeneity and Short-Term Physical Risk in Restrictive Anorexia Nervosa

CONTEXT The relevance of hormonal assessment in anorexia nervosa (AN) management is still unclear. The short-term physical risk during undernutrition period of the disease is partially predicted by anthropometric and electrolytic parameters. OBJECTIVE The objective of the study was to evaluate hormonal profiles in a large cohort of AN and their relationship with critical states. DESIGN AND SETTING This was an observational monocentric cross-sectional study performed in the endocrinological unit. PATIENTS AND OTHER PARTICIPANTS Participants included 210 young female subjects with restrictive-type AN and 42 female controls of comparable age. MAIN OUTCOME MEASURES The following hormonal parameters were measured: thyroid hormones, GH, IGF-I, cortisol, oestradiol, FSH, LH, SHBG, dehydroepiandrosterone sulfate, plasma metanephrines, and bone markers. Their relation with registered short-term evolution of AN subjects after hormonal assessment was evaluated. RESULTS Except for metanephrines and dehydroepiandrosterone sulfate, most of the hormonal abnormalities previously reported in AN were confirmed. The manifestation of these hormonal abnormalities started below different body mass index (BMI) levels, ranging between 17 and 15 kg/m(2), even though an important percentage of normal values for every parameter was still noticed for very low BMIs. All patients who developed critical states during the 3 months after the hormonal assessment presented with BMI less than 15 kg/m(2) and a very increased level of cortisol, GH, and increased values of metanephrines. CONCLUSIONS The hormonal response to undernutrition is heterogeneous in a large population with restrictive AN. In clinical practice, metanephrines, GH, and/or cortisol data could be used as important predictors for severe short-term outcome.

Weight gain reverses bone turnover and restores circadian variation of bone resorption in anorexic patients

The present study was conducted in order to describe the variations and circadian rhythm of biochemical markers of bone remodelling at baseline and after weight gain in patients with aneroxia nervosa (AN).

Organic Background of Restrictive-Type Anorexia Nervosa Suggested by Increased Serotonin1A Receptor Binding in Right Frontotemporal Cortex of Both Lean and Recovered Patients: [18F]MPPF PET Scan Study

BACKGROUND Serotonin (5-HT) pathway abnormalities were demonstrated in anorexia nervosa (AN). Brain imaging studies on 5-HT receptors support this evidence. 4-(2-methoxyphenyl)-1-[2-(N-2-pyridinyl)-p-fluorobenzamido]-ethylpiperazine ([(18)F]MPPF) is a selective 5-HT(1A) receptor antagonist with an affinity close to that of endogenous 5-HT. METHODS In 24 subjects including 8 lean restrictive-type AN patients, 9 recovered from restrictive-type AN subjects and 7 age-matched control subjects, we assessed in vivo brain [(18)F]MPPF binding by positron emission tomography and eating-related psychopathological traits. Inter-groups differences in [(18)F]MPPF binding were evaluated by voxel-based analyses. RESULTS Restrictive AN patients presented increased [(18)F]MPPF binding in a selective area of the right cortex including part of the superior temporal gyrus, inferior frontal gyrus, parietal operculum, and temporoparietal junction. Striking regional similarities of increased [(18)F]MPPF binding were found in recovered from AN subjects. Most of the psychiatric scores were increased in restrictive AN patients, and elevated perfectionism and interpersonal distrust scores were noticed in subjects recovered from AN. CONCLUSIONS The persistent increased 5-HT(1A) receptor binding in frontotemporal region of recovered AN concomitantly with specific psychopathological traits support the hypothesis of an organic dysfunction of this area and corroborates with previous literature reports of AN cases induced by temporal lesions.

Diminution de la mortalité et stabilité du taux de guérison dans le suivi de l’anorexie mentale

Resume Objectif L’anorexie mentale (AM) est un trouble du comportement alimentaire associant une denutrition, une amenorrhee et un trouble de l’image corporelle selon les criteres du DSM-IV. Peu d’etudes de suivi ont ete publiees. Nous avons realise une etude retrospective, portant sur la population de patientes anorexiques mentales restrictives ayant ete prises en charge de 1979 a 2004. Methodes Les donnees necessaires, elaborees a partir de l’inventaire de Morgan et Russell, ont ete recueillies entre mai et juillet 2004 a l’aide du dossier clinique et d’une enquete telephonique. Pour chaque patiente, ont ete notes la chronologie de la maladie, les caracteristiques morphologiques, le type de l’anorexie, le mode de prise en charge, l’histoire gynecologique et la situation professionnelle et conjugale. Resultats La population etudiee representait 206 patientes pour lesquelles la duree moyenne de suivi a ete de 8,3 ± 5,3 ans ; 55,8 % ont ete gueries sur les criteres IMC > 17,5 kg/m2 maintenu pendant 1 an et reprise de l’activite genitale ; 18,5 % sont entrees dans une forme chronique de la maladie et 25,7 % avaient encore une des deux composantes citees ci-dessus. Le taux de mortalite a ete de 1,8 %. En termes d’evolution de la maladie, l’âge de debut precoce lors de l’adolescence etait de bon pronostic. Par contre, l’intensite de la maigreur, un delai de prise en charge long, une frequence faible de consultation semblaient predictifs d’une issue defavorable. Conclusions La gravite de cette maladie est plutot liee a ses formes chronicisees qu’au nombre de deces qui lui sont directement imputables. Par contre, le versant psychopathologique n’a pas ete pris en compte et il semble important a evaluer puisque certains traits de personnalite sous-jacents apparaissent comme des facteurs de comorbidite.

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.

1895 – Cerebral opioid activity in patients with restricting-type anorexia nervosa before and after weight recovery: a [11c]diprenorphine pet study

Introduction Opioid peripheral abnormalities were described in anorexia nervosa (AN). Until now no data have been published on cerebral activity of opioid system in these subjects. Diprenorphine is a ligand with non-specific binding to opiates receptors μ, κ and δ. Aim To evaluate in vivo brain opioid receptors binding potential (BP) in patients with lean and recovered from restrictive-type AN by comparison with controls and the relationship with eating-related psychochological and hormonal traits. Methods In 17 lean restrictive-type AN patients, 15 recovered AN subjects and 15 age-matched controls we assessed in vivo [ 11 C]Diprenorphine binding by brain positron emission tomography and eating-related psychopathological traits. Inter-groups differences in [ 11 C]Diprenorphine binding were evaluated by voxel-based analyses. Results Lean restrictive AN and recovered AN patients presented with similar decreased [ 11 C]Diprenorphine binding in bilateral medial frontal cortex and temporo-parietal cortex. We noted a lower BP in hypothalamo-pituitary structures and also in anterior cingulate gyrus in lean AN patients. Additionally, only recovered AN patients presented with a decreased [ 11 C]Diprenorphine binding in caudate nuclei and putamen. Direct correlations were found between the anterior cingulate gyrus BP and mean cortisol and between the left amygdala [ 11 C]Diprenorphine binding and eating concern score. Conclusion The opioid system is widely affected in AN even after recovery in regions known to be involved in the neurocircuitry of addiction and support the hypothesis of an organic dysfunction in AN.

1611 – Opiate substitution therapy: a retrospective study of an 11-year follow-up depending on the given treatment: methadone and/or buprenorphine

Introduction After 50 years of international experience and 15 years of use in France, the positive impact of drug replacement treatments on the care of patients with opiates dependence is now well established. Even though there is a vast literature on the two existing treatments (methadone and high-dosage buprenorphine), few works have focused on patients who have changed replacement therapy during follow-up. Objectives and aims The aim of our study was to analyze the follow-up of substituted patients throughout an 11-year period. Patients were characterized by the type of treatment: methadone only, high-dosage buprenorphine only, or both treatments. Methods These groups of patients were studied depending on their characteristics at the beginning of the treatment (sociodemographic data, addictive behaviours, psychiatric assessment) and in terms of healthcare and follow-up regularity. We also tried to bring to light predictive factors of unstable follow-ups at the point of entry in healthcare. Results 891 patients were included in our results. Patients having had two substitution treatments initially present with higher severity in terms of socio-professional integration, addictive behaviours and psychiatric comorbidity. Their treatment is more discontinued and they have longer healthcare. Conclusions Psychiatric comorbidities and poly-drug use seem to characterize unstable patients who jeopardize our treatments. They have to be identified very early in order to better adjust healthcare. This preliminary work underlines the necessity of carrying out a prospective study integrating better adapted assessment tools.