René Klinkby Støving

A review of endocrine changes in anorexia nervosa

Anorexia nervosa is a syndrome of unknown etiology. It is associated with multiple endocrine abnormalities. Hypothalamic monoamines (especially serotonin), neuropeptides (especially neuropeptide Y and cholecystokinin) and leptin are involved in the regulation of human appetite, and in several ways they are changed in anorexia nervosa. However, it remains to be clarified whether the altered appetite regulation is secondary or etiologic. Increased secretion of corticotropin-releasing hormone and proopiomelanocortin seems to be secondary to starvation, however, there is evidence that it may maintain and intensify anorexia, excessive physical activity and amenorrhea. Hypothalamic amenorrhea, which is a diagnostic criterion in anorexia nervosa, is not solely related to the low body weight and exercise. Growth hormone resistance with low production of insulin-like growth factor I and high growth hormone secretion reflect the nutritional deprivation. The nutritional therapy of patients with anorexia nervosa might be improved by administering an anabolic agent such as growth hormone or insulin-like growth factor I. So far none of the endocrine abnormalities have proved to be primary, however, there is increasing evidence that some of these might participate in a vicious circle.

Gender differences in outcome of eating disorders: a retrospective cohort study.

Eating disorders (EDs) are uncommon in males. The majority of outcome studies on ED have not presented gender-specific results, mostly because of small study samples or exclusion of males. Furthermore, psychometric tools and outcome criteria used in ED have mainly been validated for females only. The objective of this study was to evaluate gender differences in weight restoration in different EDs. We studied the male representation and outcome in a large retrospective single centre cohort, the Funen Anorexia Nervosa Study (FANS). A total of 1015 patients were included in the study. A total of 356 (35%) patients were diagnosed with anorexia nervosa (AN), 298 (29%) with eating disorder not otherwise specified (EDNOS) and 361 (36%) with bulimia nervosa (BN). The male fractions in AN and EDNOS were similar, but significantly lower in BN. When remission was defined as body weight restoration to at least 85% of ideal body weight (IBW) and no self-reported binge or purgative behaviors in six months, the median time from onset to remission for patients with AN was significantly shorter for males: 7 years for females vs. 3 years for males. Among patients with a 5 years history of disease, remission rates in AN were 39% for females vs. 59% for males. The median time to remission for patients with EDNOS was similar to that of AN: 6 years for females vs. 3 years for males. In patients with EDNOS, 45% of the females remitted within 5 years vs. 77% of the males. With regard to body weight restoration and remission of purging behavior, this study suggests a better outcome for males than for females.

Diurnal variation of the serum leptin concentration in patients with anorexia nervosa

In rodents, leptin is involved in regulating eating behaviour, fat storage, and reproductive function. In humans, the serum leptin concen_tration in obese and normal weight subjects correlates with body mass index, reflecting the body fat store. The serum leptin exhibit diurnal variation, however, this has been reported to be absent in normal weighted amenorrheic athletes. Anorexia nervosa is associated with multiple endocrine abnormalities. Hypothalamic amenorrhoea often precedes the weight loss and may persist after weight recovery. We hypothesized that leptin could be involved in the regulation of eating behaviour and gonadal function in anorexia nervosa.

Do Postoperative Psychotherapeutic Interventions and Support Groups Influence Weight Loss Following Bariatric Surgery? A Systematic Review and Meta-analysis of Randomized and Nonrandomized Trials

Bariatric surgery is currently considered the most effective treatment of severe obesity, but considerable individual variations in weight loss results have been reported. We therefore conducted a systematic review and meta-analysis of studies investigating the effect of psychotherapeutic interventions and support groups on weight loss following bariatric surgery. A literature search was conducted in the databases PubMed and PsycINFO, identifying nine eligible studies reporting results of the effect of psychotherapeutic interventions and support groups on weight loss following bariatric surgery. The results revealed a statistically significant overall effect of both psychotherapeutic interventions and support groups on weight loss (pooled effect size correlation (ESr) = 0.18; p < 0.0001). When comparing the effect sizes of psychotherapeutic interventions and support groups, no difference was found (p = 0.51). Higher quality studies had smaller effect sizes (0.16) than studies with low quality scores (0.22), but the difference did not reach statistical significance (p = 0.26). Patients attending psychotherapeutic interventions or support groups in combination with bariatric surgery appeared to experience greater weight loss results than patients treated with bariatric surgery only. However, research in this area is characterized by a lack of methodological rigor, and it is recommended that future study designs include randomization and active attention control conditions.

Quality of life in eating disorders: A meta-analysis

Eating disorders (EDs) comprise a variety of symptoms and have a profound impact on everyday life. They are associated with high morbidity and mortality. The objective of this study was to analyse published data on health-related quality of life (HRQoL) in EDs so as to compare the results to general population norm data and to investigate potential differences between ED diagnostic groups. A systematic review of the current literature was conducted using a keyword-based search in PubMed and PsychInfo. The search covered anorexia nervosa (AN), bulimia nervosa (BN), eating disorders not otherwise specified (EDNOS) and binge eating disorder (BED) and used the Medical Outcomes Study Short Form-36 Health Survey (SF-36) as a measure of HRQoL. Of the 102 citations identified, 85 abstracts were reviewed and seven studies were included in the meta-analysis. AN patients were included in five studies (n=227), BN in four studies (n=216), EDNOS in two studies (n=166) and BED in four studies (n=148). We tested for between-study variation and significant differences between the diagnostic groups. The results confirmed a significantly lower level of HRQoL in all EDs compared to a population mean. It was not possible to establish any differences between the diagnostic groups.

Psychological characteristics and associations with weight outcomes two years after gastric bypass surgery: Postoperative eating disorder symptoms are associated with weight loss outcomes

This study investigated symptoms of eating disorder, depression, and anxiety among Roux-en-Y gastric bypass patients two years after surgery, and the relationship between these characteristics and weight loss. Respondents completed assessment questionnaires including Eating Disorder Inventory-2 (EDI-2), Harvard Anxiety and Depression Scale (HADS), and questions related specifically to binge eating. Forty-five patients (8 men, 37 women) out of 65 (67%) responded. Scores were significant higher on impulse regulation, interoceptive awareness, ineffectiveness, maturity fears and interpersonal distrust in comparison with a Danish norm group (p≤0.05). The weight losses obtained after surgery varied from 12 to 60% of the starting weights. Binge eating and ineffectiveness were found to significantly correlate with weight loss variations after surgery (p≤0.05). The results of this study indicate that knowledge of the potential influence of eating disorder symptoms on outcomes after bariatric surgery is needed in order to optimize weight outcomes following surgery.

Dronabinol in severe, enduring anorexia nervosa: A randomized controlled trial

OBJECTIVE The evidence for pharmacological treatment of severe, longstanding anorexia nervosa (AN) is sparse and the few controlled pharmacologic studies have focused on a narrow range of drugs. The aim of the present study was to investigate the effects of treatment with a synthetic cannabinoid agonist on body weight and eating disorder-related psychopathological personality traits in women with severe, enduring AN. METHOD This add-on, prospective, randomized, double blind, controlled crossover study was conducted between 2008 and 2011 at a specialized care center for eating disorders. Twenty-five women over 18 years with AN of at least 5 years duration were randomized to treatment with either dronabinol-placebo or placebo-dronabinol. In addition to the standardized baseline therapeutic regime, the participants received dronabinol, 2.5 mg twice daily for 4 weeks and matching placebo for 4 weeks, separated by a 4-week wash-out period. Primary outcome was the mean change in body weight. Secondary outcome was score changes on the Eating Disorder Inventory-2 (EDI-2). Data were analyzed for the 24 patients who completed the trial. RESULTS During dronabinol treatment, participants gained 0.73 kg (t = 2.86, df = 22, p < 0.01) above placebo without significant psychotropic adverse events. Dronabinol significantly predicted weight gain in a multiple linear regression including EDI-2 body dissatisfaction score and leptin. EDI-2 subscale scores showed no significant changes over time. DISCUSSION Dronabinol therapy was well tolerated. During four weeks of exposure it induced a small but significant weight gain in the absence of severe adverse events.

Indirect evidence for decreased hypothalamic somatostatinergic tone in anorexia nervosa

objective In animals, somatostatin (SRIH) and growth hormone (GH)‐releasing hormone (GHRH) increase feeding via a common neural mechanism. Furthermore, SRIH counteracts the suppressive action of corticotrophin‐releasing hormone (CRH) on food intake. Hypothetically, SRIH could be involved in the central feeding mechanism in anorexia nervosa (AN). Peripheral administration of pyridostigmine (PD) minimizes the release of hypothalamic SRIH.

Update on endocrine disturbances in anorexia nervosa

The marked endocrine changes that occur in anorexia nervosa have aroused a great deal of interest, and over the last decade much research has been conducted in this field. The endocrine disturbances are not specific to this disorder, as they also occur in starvation states secondary to other causes, and they return to normal upon weight restoration. However, emaciation may have profound effects on psychological processes, establishing an intricate circular interaction whereby somatic and psychological manifestations of starvation may continue to act. The purpose of this paper is to provide an overview of the large body of literature concerning endocrine aspects of anorexia nervosa with the main focus on the latest results, which provide leads for potential etiological theories.

Fetal antigen 1 (FA1), a circulating member of the epidermal growth factor (EGF) superfamily: ELISA development, physiology and metabolism in relation to renal function

We describe an ELISA technique for quantification of fetal antigen 1 (FA1), a glycoprotein belonging to the EGF-superfamily. The ELISA is based on immunospecifically purified polyclonal antibodies and has a dynamic range of 0.7-5.3 ng/ml, intra- and inter-assay C.V.s of less than 3.2% and an average recovery of 105% in serum and 98% in urine. Comparison of FA1 in amniotic fluid, serum and urine revealed parallel titration curves, identical elution volumes following size chromatography, immunological identity and similar profiles when analysed by MALDI-MS. The reference interval for serum FA1 was 12.3-46.6 ng/ml and the levels were 10 times higher in patients with renal failure. FA1 showed no diurnal variation, no variation during the menstrual cycle and was not influenced by the acute phase reaction. In humans (n = 10) the renal clearance of FA1 was 11 ml/min and an identical high renal clearance was found in rats when expressed per 100 g body weight. In rats the initial increase in serum FA1 was 10 ng/ml/h following bilateral nephrectomy, explaining the increased serum concentrations of FA1 observed in patients with renal failure.