Bruno Estour

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.

Ghrelin and Obestatin Circadian Levels Differentiate Bingeing-Purging from Restrictive Anorexia Nervosa

CONTEXT Anorexia nervosa (AN) patients present with restrictive food behavior (AN-R). Some of them develop episodes of bulimia (AN-BP) without any clear pathophysiological explanation to date. Their clinical differentiation is important but not easily performed. Orexigenic/anorexigenic peptides measurements could provide some clues for that matter. OBJECTIVE The objective of the study was to determine whether the circadian profile of total and acylated ghrelin, obestatin, and peptide YY (PYY) levels is different in AN-R subjects when compared with AN-BP patients. DESIGN AND SETTINGS This was a cross-sectional study in an endocrinological unit. PATIENTS AND CONTROL SUBJECTS Four groups of age-matched young women: 22 AN-R, 10 AN-BP, 16 normal-weight bulimia nervosa (BN), and nine controls. MAIN OUTCOME MEASURES Twelve-point circadian profiles of plasma total and acylated ghrelin, obestatin, and PYY were measured. RESULTS Total and acylated ghrelin and obestatin circadian levels were increased in AN-R when compared with controls but decreased in both AN-BP and BN groups (P < 0.001). PYY was decreased in all groups with eating disorders. Acylated to total ghrelin ratio was decreased in AN-BP and BN (P < 0.001), whereas obestatin to acylated ghrelin and PYY to acylated ghrelin ratios were increased in both groups with bingeing-purging behavior (P < 0.0001). CONCLUSIONS Patients with AN-associated bingeing-purging behavior present a very different profile of appetite regulatory peptides when compared with the pure restrictive type. The assessment of ghrelin (and eventually obestatin) could be of particular interest for differential diagnosis. Very low ghrelin levels and increased anorexigenic to orexigenic peptide ratios suggest either a lack of adaptation to a starvation state or a higher facility to cope with undernutrition.

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.

Global DNA methylation evaluation: potential complementary marker in differential diagnosis of thyroid neoplasia

The implications of global DNA hypomethylation were recently reported in several models of tumorigenesis. Little is known about this epigenetic event in thyroid neoplasia. The study aimed to evaluate the status of global DNA methylation in several types of thyroid tumors using a monoclonal antibody specific for 5-methylcytidine (5-mc) and to define the diagnosis potential of this marker. 5-mc immunostaining scores were calculated in 17 papillary thyroid carcinomas (PTC), 6 follicular thyroid carcinomas (FTC), 16 follicular adenomas (FA), 19 nodular goiters (NG) and ten Hürthle cells adenomas (HCA). The expression of galectin-3 was also evaluated. Computerized image analysis showed a significant lower level of 5-mc immunostaining in thyroid carcinoma when compared with benign tumors or adjacent normal thyroid parenchyma (P<0.0001). Overall, 5-mc accuracy to distinguish malign from benign thyroid tumors was similar to that of galectin-3 (89% versus 87%, P>0.05). The combination of 5-mc with galectin-3 led to an excellent accuracy level of 96%. Among follicular neoplasia 5-mc accuracy to differentiate malign tumors trends to be higher than galectin-3 one (90% versus 66%, P=0.06). These data stress the necessity of epigenetic events evaluation among thyroid nodules and propose global DNA methylation assessment as a potential diagnostic tool to combine with other valuable markers.

Orexigenic Neuropeptide 26RFa: New Evidence for an Adaptive Profile of Appetite Regulation in Anorexia Nervosa

CONTEXT Restrictive anorexia nervosa (AN) presents an adaptive appetite regulating profile including mainly high levels of ghrelin. Because this adaptive mechanism is not effective on food intake, other appetite-regulating peptides need to be explored. 26RFa is a hypothalamic neuropeptide that stimulates appetite, gonadotropin release, and bone metabolism. OBJECTIVE The objective of the study was to evaluate the circadian levels of 26RFa in AN patients compared with healthy subjects, other eating disorders, and constitutional thinness (CT). DESIGN AND SETTINGS This was a cross-sectional study performed in an endocrine unit and an academic laboratory. INVESTIGATED SUBJECTS Five groups of age-matched young women were included in the study: 19 restrictive AN, 10 AN with bingeing/purging episodes, 14 with CT, 10 bulimic, and 10 normal-weight controls. MAIN OUTCOME MEASURES Twelve-point circadian profiles of plasma 26RFa levels were measured in each subject. RESULTS Significant circadian variations of 26 RFA were noticed in controls with higher values in the morning and abrupt decrease at noon. Twenty-four-hour mean 26RFa levels were significantly increased in restrictive AN and AN with bingeing/purging episodes (P < 0.001), predominantly in the afternoon and evening when compared with controls. Preprandial rises of 26 RFA were noticed in AN patients. Mean 26RFa levels trend to be higher in CT than in controls (P = 0.06) and significantly lower than in AN. The bulimic patients presented a circadian profile of 26RFa similar to that of controls. CONCLUSION High levels of circulating 26RFa observed in AN patients might reflect an adaptive mechanism of the organism to promote energy intake and to increase fat stores in response to undernutrition.

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.

Papillary thyroid microcarcinoma: incidence and prognostic factors

The objective of this study was to define the prognostic factors of papillary microcarcinoma of the thyroid (PMCT), and to analyse their epidemiologic and histopathologic characteristics. Our series included 57 patients diagnosed with PMCT between 1994 and 2003 among 944 patients who underwent thyroid surgery. All the surgical specimens were examined in the same department of pathology using the same technique. The prognostic factors were elaborated from the results of the histological examination. The epidemiological and histopathological characteristics were also evaluated. Two sub-groups were distinguished: patients with node disease and/or with metastasis (17 patients) and patients without node disease and metastasis (40 patients). The architecture of PMCT was papillary in 14% of cases, follicular in 35% of cases and mixed in 49% of cases, with no significant difference between any two groups. Histopathologic characteristics such as the vascular extension, infiltration into the adjacent parenchyma or in the thyroid capsule are all indicative of a poor prognosis. Two categories of PMCT, with and without the risk of metastatic spread, can be identified from these prognostic factors.

Constitutional Thinness and Anorexia Nervosa: A Possible Misdiagnosis?

Clinical and biological aspects of restrictive anorexia nervosa (R-AN) are well documented. More than 10,000 articles since 1911 and more than 600 in 2013 have addressed R-AN psychiatric, somatic, and biological aspects. Genetic background, ineffectiveness of appetite regulating hormones on refeeding process, bone loss, and place of amenorrhea in the definition are widely discussed and reviewed. Oppositely, constitutional thinness (CT) is an almost unknown entity. Only 32 articles have been published on this topic since 1953. Similar symptoms associating low body mass index, low fat, and bone mass are reported in both CT and R-AN subjects. Conversely, menses are preserved in CT women and almost the entire hormonal profile is normal, except for leptin and PYY. The aim of the present review is to alert the clinician on the confusing clinical presentation of these two situations, a potential source of misdiagnosis, especially since R-AN definition has changed in DSM5.