Increased risk of somatic diseases following anorexia nervosa in a controlled nationwide cohort study.

OBJECTIVE: To assess the risk of somatic diseases in connection with anorexia nervosa (AN). METHOD: This matched cohort study was based on Danish registries of all patients born 1961-2008 with a first-time diagnosis of AN in 1994-2018 at age 8-32 and matched controls without an eating disorder. For 13 somatic disease categories, time from inclusion date to time of first somatic diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9985 AN patients born 1961-2008 and 49,351 controls were followed for a median (interquartile range) of 9.0 (4.4-15.7) years. During the first 2 years after entry there was a 60% higher hazard for any somatic disease among patients with AN than among controls, while the ratio from three to 11 years was reduced to 1.18. Regardless of age at diagnosis, the hazard among patients and controls were no different at approximately a decade after diagnosis of AN and the cumulative risk for patients for 12 of 13 disease categories was always higher or no less that for controls. For all disease categories, the hazard ratio (HR) was higher when close to entry. For most disease categories, age at diagnosis of AN did not modify the effect. DISCUSSION: While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls. Large HRs were seen in the early years after diagnosis during which patients require extensive medical interventions. PUBLIC SIGNIFICANCE: Based on Danish registries, a large sample of almost 10,000 patients with AN born 1961-2008 and almost 50,000 matched controls were followed for a median of 9 years. While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls.

Comorbid mental disorders during long-term course in a nationwide cohort of patients with anorexia nervosa.

OBJECTIVE: Comorbid mental disorders in anorexia nervosa during long-term course require detailed studies. METHOD: This matched cohort study was based on nationwide Danish register data of all patients born 1961-2008 with a first-time ICD-10 diagnosis of anorexia nervosa (AN) between 1994 and 2018 at age 8-32 and matched controls taken from all individuals without an eating disorder (ED). For nine categories of non-eating mental disorders, time from date of first AN-diagnosis (inclusion date) to time of first diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9,985 patients with AN (93.5% females) and 49,351 matched controls were followed for a median (IQR) of 9.0 (4.4-15.7) years. For patients, there was about 25% and 55% risk of receiving any non-ED disorder during the first 2 years and two decades after inclusion, respectively. A hazard ratio (HR) of seven for any non-ED was found for the first 12 months after inclusion, a ratio that reduced to two at five or more years after inclusion. During the first years, large HRs ranging in 6-9 were found for affective, autism spectrum, personality, and obsessive-compulsive disorders with the latter displaying the highest continuous increased risk. The HR at 12 months after inclusion was highest for any non-ED disorder and affective disorders in patients aged 8-13 at diagnosis. DISCUSSION: Comorbid mental disorders in AN are most frequently diagnosed in the first years after diagnosis of AN and on longer terms imply a double immediate risk.

Patient- and clinician- reported outcome in eating disorders.

Patient-reported outcome is increasingly applied in health sciences. Patients with eating disorders (EDs) characteristically have a different opinion of their needs to that of the health professionals, which can lead to ambivalence towards treatment and immense compliance difficulties. This cross-sectional study compared data assessed by the clinician to patient-reported measures in patients with a history of EDs. We included data from a cohort of patients with EDs (n=544) referred to a specialized ED unit in Denmark. Patient-reported measures included the Eating Disorder Inventory-2 (EDI-2) and the Short Form 36 (SF-36), and clinical data included remission status and body mass index (BMI). We found a positive association between BMI and EDI-2 scores for anorexia nervosa (AN) and eating disorder not otherwise specified (EDNOS), reflecting increasing ED symptomatology with increasing BMI. This association was not observed in bulimia nervosa (BN). We did not find a correlation between SF-36 scores and BMI in any of the diagnostic groups.

Does specialization of treatment influence mortality in eating disorders?--A comparison of two retrospective cohorts.

Eating disorders (EDs) are psychiatric disorders associated with high morbidity and mortality. It is well established that patients with anorexia nervosa (AN) have an increased risk of premature death, whereas mortality data are lacking for the other EDs. This study aimed to establish mortality rates in a sample of ED patients (n=998) with a mean follow-up of 12 years. This was compared to previous data from the same catchment area before a multidisciplinary centre was established. The standardized mortality ratio (SMR) was calculated. To compare the two cohorts, adjusted crude ratios were calculated with the confounding variables: body mass index (BMI), age at referral and diagnosis. In the latest cohort the SMR for AN was 2.89 vs 11.16 in the time before our specialization. SMR for bulimia nervosa (BN) and for eating disorder not otherwise specified (EDNOS) in the latest cohort were 2.37 and 1.14 respectively. When comparing two retrospective cohorts it is not possible to draw a definite conclusion, however the present study supports that integrating a somatic unit in a multidisciplinary centre may have a favourable influence on mortality in AN.

Serum levels of fetal antigen 1 in extreme nutritional States.

Objective. Recent data suggest that fetal antigen (FA1) is linked to disorders of body weight. Thus, we measured FA1 serum levels in two extreme nutritional states of morbid obesity (MO) and anorexia nervosa (AN) and monitored its response to weight changes. Design. FA1 and insulin serum concentrations were assessed in a cross-sectional study design at defined time points after gastric restrictive surgery for 25 MO patients and 15 women with AN. Results. Absolute FA1 serum levels were within the assay normal range and were not different between the groups at baseline. However, the ratio of FA1/BMI was significantly higher in AN. FA1 was inversely correlated with BMI before and after weight change in AN, but not in MO patients. In addition, MO patients displayed a significant concomitant decrease of FA1 and insulin with the first 25% of EWL, while in AN patients a significant increase of FA1 was observed in association with weight gain. Conclusion. FA1 is a sensitive indicator of metabolic adaptation during weight change. While FA1 serum levels in humans generally do not correlate with BMI, our results suggest that changes in FA1 serum levels reflect changes in adipose tissue turnover.

Purging behavior in anorexia nervosa and eating disorder not otherwise specified: a retrospective cohort study.

Purging behavior in eating disorders is associated with medical risks. We aimed to compare remission rates in purging and non-purging females with anorexia nervosa (AN) and eating disorder not otherwise specified (EDNOS) in a large retrospective single center cohort. A total of 339 patients with AN and 266 patients with EDNOS were included in the study. The proportion of subjects with purging behavior at least once a week during the last 3 months was similar in the two groups: 22% in AN and 24% in EDNOS. Remission was defined by a goal weight ≥85% of ideal body weight and no reported purging behavior in the last 6 months. The median time from onset to remission for patients with AN was 7 years for the non-purging vs. 11 years for the purging patients. The purging AN patients with both vomiting and laxative abuse displayed the poorest course. Among EDNOS patients, the time to remission was also significantly longer for purging patients compared to non-purging patients. Thus, in line with previous studies, we found that purging behavior is associated with delayed time to remission in treatment-seeking AN and EDNOS patients. This study provides evidence to support the retention of the diagnostic sub-typing in AN.

Reflections on involuntary treatment in the prevention of fatal anorexia nervosa: a review of five cases.

OBJECTIVE: Involuntary treatment in the prevention of fatal anorexia nervosa (AN) is still controversial. METHOD: Five fatal cases of AN were identified out of 1,160 patients who attended a specialized eating disorder unit between 1994 and 2006. Information on inpatient, ambulatory, and emergency room treatment was extracted from a population-based registration system. RESULTS: Personality disorders were diagnosed in all five patients and substance abuse in three patients. In all cases, illness duration was more than 10 years and late onset was seen in two cases. None of the deaths were due to suicide. Involuntary hospital admission was instituted for three patients, but only one patient was compulsory detained more than once. Four patients died after having discontinued treatment. DISCUSSION: Compulsory treatment may be of crucial importance in the prevention of fatalities in patients with long-standing AN and psychiatric comorbidity who discontinue treatment.

Is glycyrrhizin sensitivity increased in anorexia nervosa and should licorice be avoided? Case report and review of the literature.

OBJECTIVE: Hypokalemia is a potentially life-threatening electrolyte disturbance in anorexia nervosa and is most frequently caused by purging behavior. We report a case of severe hypokalemia in anorexia nervosa induced by daily ingestion of approximately 20 g of licorice. METHODS: To confirm the diagnosis of licorice-induced pseudohyperaldosteronism, a re-exposure trial was performed. RESULTS: Cessation of the licorice intake normalized plasma potassium, renin, and aldosterone levels and the urine cortisol/cortisone ratio. Re-exposure confirmed the diagnosis. The pronounced response to a relatively low daily dose of licorice suggests high glycyrrhizin sensitivity. CONCLUSION: Patients with anorexia nervosa not only have decreased food intake but also selective and sometimes bizarre eating habits that, in association with increased sensitivity to glycyrrhizin, may cause severe hypokalemia.

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.

Remission of eating disorder during pregnancy: five cases and brief clinical review.

Eating disorder during pregnancy is associated with a diversity of adverse outcomes and is of potential danger to both mother and child. There is, however, a tendency for remission of the eating disorder during pregnancy with improvement of symptoms such as restrictive dieting, binging and purging, and some women actually manage to put the disease behind them. This case report describes five women with different eating disorders and focuses on the symptomatology during pregnancy and in the months postpartum. The discussion deals with the possible psychological, social and endocrinological reasons for remission and the subsequent relapse, the definition of recovery and the factors which should alert health care professionals of the at-risk pregnancies in cases of undisclosed eating disorder. Furthermore, therapeutic interventions are proposed.

Slow-growing craniopharyngioma masquarading as early-onset eating disorder: two cases.

BACKGROUND: Craniopharyngiomas are slow-growing tumors, which can either be asymptomatic or present themselves with visual, neuropsychiatric or endocrine disturbances. Eating disorders (EDs) are syndromes with unknown etiology, associated with multiple endocrine abnormalities. In pediatric cases the presentation of EDs may differ markedly from those of adults. OBJECTIVE: We report on two pediatric patients with craniopharyngioma misinterpreted as ED. METHOD: Available patient records, psychiatric examinations, neuro-radiographic imaging, and biochemical data were evaluated. DISCUSSION: The reported cases illustrate the importance to consider slow-growing craniopharyngioma in ED. Especially in atypical ED, neuro-radiographic, ophthalmologic and endocrine examination should be carried out. Furthermore, structural hypothalamic lesions in these cases mimicking features of ED, suggesting the possibility of an as yet unidentified structural hypothalamic disorder to be implicated in the etiopathogeny of ED.

Leptin, ghrelin, and endocannabinoids: potential therapeutic targets in anorexia nervosa.

Anorexia nervosa (AN) has the highest mortality rate between psychiatric disorders, and evidence for managing it is still very limited. So far, pharmacological treatment has focused on a narrow range of drugs and only a few controlled studies have been performed. Furthermore, the studies have been of short duration and included a limited number of subjects, often heterogenic with regard to stage and acute nutritive status. Thus, novel approaches are urgently needed. Body weight homeostasis is tightly regulated throughout life. With the discovery of orexigenic and anorectic signals, an array of new molecular targets to control eating behavior has emerged. This review focuses on recent advances in three important signal systems: leptin, ghrelin, and endocannabinoids toward the identification of potential therapeutical breakthroughs in AN. Our review of the current literature shows that leptin may have therapeutic potentials in promoting restoration of menstrual cycles in weight restored patients, reducing motor restlessness in severely hyperactive patients, and preventing osteoporosis in chronic patients. Ghrelin and endocannabinoids exert orexigenic effects which may facilitate nutritional restoration. Leptin and endocannabinoids may exert antidepressive and anxiolytic effects. Finally, monitoring serum concentration of leptin may be useful in order to prevent refeeding syndrome.

[Severe anorexia nervosa: five fatal cases]. / Svaer anorexia nervosa: fem tilfaelde med fatale forløb.

The Centre for Eating Disorders at Odense University Hospital receives about 140 patients yearly. We reviewed the five lethal cases that occurred during the last 10 years. None of the patients died from suicide, which is unexpected, because patients with anorexia nervosa (AN) are known to have an increased suicide rate. Although compulsory treatment has shown to be efficient in treating AN, only three of the five patients were compulsorily admitted and only one was admitted several times. Dropout remains a significant problem in the treatment of AN, as four out of the five patients died after they had dropped out of the treatment program.

[The importance of physical activity and body mass index for body satisfaction]. / Betydningen af fysisk aktivitet og body mass index for tilfredshed med kropsbygningen.

INTRODUCTION: Body satisfaction has mostly been investigated among patients with psychiatric diseases. A few studies have found an association between physical activity, obesity and body satisfaction in the healthy population, but the focus has mostly been on the risk of developing diseases. The aim of the present study has been to study the association between body satisfaction, BMI, physical activity and chronic diseases. MATERIALS AND METHODS: A total of 15,252 women and 14,181 men born between 1953 and 1982 (both years included) and registered with The Danish Twin Registry answered a questionnaire which they were sent in 1994. We used the questions on chronic diseases, height and weight, physical activity and body satisfaction. Univariat analysis of body satisfaction and the other variables was carried out using chi2-tests and t-tests. Multivariat analysis was carried out with logistic regression. RESULTS: More men than women are satisfied with their bodies; BMI confers a negative association, while physical activity confers a positive association with body satisfaction. This satisfaction appears to some degree mediated by BMI. The presence of asthma and other lung symptoms and lower-back pain was negatively associated with body satisfaction. DISCUSSION: Thinness tends to be the ideal body image today and this may explain why more obese people are dissatisfied with their body. This ideal is more important for women s perception of their bodies. Physical activity and being healthy adds to body satisfaction.

Bioactive insulin-like growth factor (IGF) I and IGF-binding protein-1 in anorexia nervosa.

CONTEXT: Regulation of IGF-I activity appears crucial in anorexia nervosa (AN) during adaptation to chronic starvation as well as during the regenerative processes on nutritional restoration. OBJECTIVE: The objective of this study was to examine the relationship between IGF-I bioactivity and IGF-binding capacity as expressed as formation of the binary complex of IGF-binding protein-1 (IGFBP-1) and IGF-I in patients with AN at different stages and with different subtypes of the disease. DESIGN: This was a longitudinal study. SETTING: The study took place at a clinical research center at a university hospital. STUDY PARTICIPANTS: We studied a total of 45 women with AN and 24 age-comparable healthy controls. MAIN OUTCOME MEASURES: IGF-I bioactivity was determined using an IGF-I receptor activation assay, and IGF-I/IGFBP-1 complex formation was determined by an assay that allows direct determination of the binary complex. RESULTS: IGF-I bioactivity was significantly decreased in serum from patients with AN. We found significant correlations between total, ultrafiltered free, and bioactive IGF-I. Despite increased IGFBP-1 concentrations, levels of IGF-I/IGFBP-1 binary complex were not significantly increased in AN. Oral contraceptives were associated with increased levels of IGF-I, IGFBP-1, and binary complex formation. Ghrelin levels were only significantly raised in those patients who had lost more than 5% of the body weight during the last 4 wk, whereas ghrelin levels in weight-stable as well as in weight-gaining patients did not significantly differ from the controls. CONCLUSIONS: Total IGF-I level is a suitable marker of IGF-I bioactivity in emaciated patients with AN irrespective of the clinical subtype and acute nutritional state.

[Suicidal behaviour in a clinical population of 12- to 17-year-old patients with eating disorders]. / Suicidal adfaerd i en klinisk population af 12-17-årige med spiseforstyrrelser.

INTRODUCTION: The aim of this study was to determine the prevalence of suicidal behavior and comorbidity among patients 12-17 years of age with eating disorders. Previous studies showed an increased rate of suicidal behavior in young people with eating disorders. MATERIALS AND METHODS: Data were collected as part of a European study concerning eating disorders. 37 patients (12-17 years, mean age 15 years) from the Center for Eating Disorders, Odense University Hospital, participated in the study. The frequency of suicidal behavior was tested individually by BAB-T interview (''Grading of Anorexia and Bulimia, Teen-ager''), which is a semi-structured interview with the patient, and by YSR (''Youth Self Report'') a questionnaire filled in by the patient herself. RESULTS: Suicidal behavior was shown by 40% of the patients, and 29% had self-injurious behavior. There was a tendency for suicidal behavior and comorbidity to be more prominent in the youngest patients. CONCLUSION: The risk of suicidal behavior is greater in patients with eating disorders than in the background population. In the youngest patients there is an increased tendency to suicidal behavior and comorbidity, but this requires further documentation. The clinician must be aware of self-injurious behavior in patients with eating disorders, including those between 12 and 17 years of age.