Thyrotropin, prolactin, and growth hormone responses to thyrotropin-releasing hormone in anorexia nervosa and bulimia

Serum thyrotropin (TSH), prolactin (PRL), and growth hormone (GH) levels were measured before and after stimulation with thyrotropin-releasing hormone (TRH) in 10 patients with bulimia, 7 with features of the restricting subtype of anorexia nervosa, and 6 with bulimic subtype of anorexia nervosa. The mean basal levels of TSH, PRL, and GH did not differ among the three groups. A delayed TSH response was found in 86% of the restricting anorectics, 80% of the bulimic anorectics, and 22% of the bulimics. The PRL response was normal in all patients, with no significant difference among the three groups. Elevated basal GH levels were found in 29% of the restricting anorectics, 33% of the bulimic anorectics, and 33% of the bulimics. An abnormal GH increase after TRH stimulation was observed in 50% of the restricting anorectics, 20% of the bulimic anorectics, and 13% of the bulimics. These results suggest that some patients with bulimia, and some with anorexia nervosa, have a hypothalamic dysfunction. These neuroendocrine abnormalities do not appear to be due solely to low weight or to metabolic changes resulting from binge eating and are not associated with depressive symptoms.     

Personality dimensions in eating disorders and their relevance for subtyping.

Personality dimensions and psychopathological symptoms were assessed in 50 female patients hospitalized for the treatment of anorexia nervosa or bulimia nervosa and in 19 healthy female controls of similar age. Restricting anorexia nervosa patients, who had lost weight by consistently reducing their food intake, reported significantly greater self-control, inhibition of emotionality, and conscientiousness than controls or bulimia nervosa patients, before and after the data were corrected for depressive and eating pathology. Both nonbulimic and bulimic anorexia nervosa patients expressed stronger than normal conformance to moral and family values. On the impulsivity dimension, bulimia nervosa patients scored in the high normal range, whereas bulimic anorexia nervosa patients rated in the low normal range. The results suggest that a personality disposition toward overcontrol and reserve might constitute a risk factor for the restricting type of anorexia nervosa through fostering restrictive behavior toward food and avoidance of personal relationships.     

Subgroups of anorexia nervosa and bulimia: validity and utility

Sociodemographic and psychodynamic similarities and differences among four subgroups of eating disordered females seeking outpatient consultations for anorexia nervosa and bulimia are presented. Supporting the spectrum concept of eating disorders, the four diagnostic subgroups are: anorexia nervosa, restricting; anorexia nervosa with bulimic complications; normal weight bulimia with a history of anorexia nervosa; and normal weight bulimia without a history of anorexia nervosa. Overall, the 165 patients are white, middle to upper-middle class females in their early twenties. The highest levels of psychopathology, as measured by the Eating Disorder Inventory, was manifested by patients afflicted with both anorexic and bulimic symptomatology, either in the past or at time of consultation. Implications for diagnostic classification and clinical intervention are discussed.     

Hypothalamic-pituitary-gonadal function in anorexia nervosa and bulimia

Patients with anorexia nervosa (AN) exhibit neuroendocrine abnormalities that may result solely from emaciation or may reflect defective endocrine mechanisms which are intrinsic to disordered eating even in the absence of starvation. To distinguish these possibilities, we have studied indices of hypothalamic-pituitary-gonadal (HPG) function in 9 patients with AN, 12 normal weight patients with bulimia and recent or current oligomenorrhea, and 8 normal weight controls. Measurement of 24-hour luteinizing hormone (LH) secretion with 30-min sampling revealed significantly fewer LH secretory spikes and a trend toward lower mean 24-hour LH levels in both bulimic and anorectic patients than in controls. Stimulation with gonadotropin releasing hormone produced elevated LH responses in the bulimic group and blunted LH responses in the anorectic group. Stimulation with estradiol revealed diminished LH augmentative responses and a trend toward diminished follicle stimulating hormone augmentative responses among bulimic as well as AN patients compared to controls. In each instance, the bulimic group tended to show within-group heterogeneity, with some individuals falling within the AN range. These findings suggest that HPG axis abnormalities in eating disordered patients cannot entirely be attributed to emaciation and that factors other than subnormal weight contribute to disturbed hypothalamic-pituitary functioning in these patients.     

Postremission predictors of relapse in women with eating disorders

OBJECTIVE: The authors sought to evaluate patterns and predictors of relapse among women with eating disorders. METHOD: Interviews were conducted biannually to annually to assess symptoms of eating disorders, axis I disorders, treatment, and psychosocial function on a weekly basis for women diagnosed with anorexia nervosa (N=136) or bulimia nervosa (N=110) and prospectively followed for 9 years. At the last follow-up, 229 (93%) of the subjects had been retained in the study group. RESULTS: Relapse occurred in 36% of the women with anorexia nervosa and 35% of the women with bulimia nervosa. Women with intake diagnoses of anorexia nervosa, restricting subtype, tended to develop bulimic symptoms during relapse, whereas women with intake diagnoses of anorexia nervosa, binge-purge subtype, or bulimia nervosa tended to return to bulimic patterns during relapse. Greater body image disturbance contributed to a risk of relapse in both eating disorders, and worse psychosocial function increased the risk of relapse in bulimia nervosa. CONCLUSIONS: These results may explain the long-term efficacy of interpersonal therapy for bulimia nervosa and suggest that focused body image work during relapse prevention may enhance long-term recovery from eating disorders.     

Abnormal caloric requirements for weight maintenance in patients with anorexia and bulimia nervosa

OBJECTIVE: This study tested previous findings that patients with eating disorders who attain normal weight have abnormal caloric requirements for maintaining weight. METHOD: Fifty-three female patients meeting the DSM-III-R criteria for anorexia nervosa and/or bulimia nervosa were divided into four subgroups, and their daily caloric intake was measured over a weight-stable period. Patients with anorexia nervosa (restricting and bulimic subtypes) were studied 4 weeks after refeeding and weight gain, when they had attained 95% of average body weight. Patients with normal-weight bulimia (previously anorexic or never previously anorexic) were studied 1-4 weeks after admission to an inpatient unit. RESULTS: After weight restoration, restricting anorexic patients required significantly more calories per day to maintain weight than did bulimic anorexic patients, as measured with corrections for weight, body surface area, and fat-free mass. Previously anorexic normal-weight bulimic patients required significantly more calories per day to maintain weight than never-anorexic normal-weight bulimic patients, as measured with correction for weight but not with the other factors used to correct caloric intake. CONCLUSIONS: To maintain stable weight after weight restoration, restricting anorexic patients require a significantly higher caloric intake than do bulimic anorexic patients. Differences in caloric needs between normal-weight bulimic patients with and without histories of anorexia may depend on the methods used to correct caloric requirements. Body surface area may be the most precise correction factor across different subgroups of eating disorder patients. Elevated caloric requirements, when coupled with reduced food intake, may particularly contribute to relapse in anorexic patients.     

Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain

Leptin plays an important role in reproductive function. In patients with acute anorexia nervosa, serum leptin levels have repeatedly been shown to be lower than in age-matched controls. We have previously hypothesized that the amenorrhea characteristic of anorexia nervosa is related to this low leptin secretion. In an attempt to address this hypothesis, serum levels of leptin and follicle stimulating hormone (FSH) and luteinizing hormone (LH) of 16 female inpatients with anorexia nervosa or an eating disorder not otherwise specified (atypical anorexia nervosa) were measured on a biweekly basis during weight gain. We hypothesized that a serum leptin level of 1.85 microg L(-1) would be associated with gonadotropin levels at or above the minimal level observed during the menstrual cycle in healthy adult fertile females. Our results revealed that increments of LH levels generally tracked increments of leptin levels during the first weeks of treatment. Similarly, in those patients with low referral leptin levels, FSH initially also tracked leptin levels. In contrast, a relationship between gonadotropin levels and leptin secretion was no longer discernible after LH and FSH levels had peaked. Those patients with exceedingly low leptin levels upon admission revealed a slow increase of gonadotropin levels. Our hypothesis of a threshold leptin level of 1.85 microg L(-1) was supported for LH only.     

Disturbances in the hypothalamo-pituitary-adrenal and other neuroendocrine axes in bulimia

Disturbances in the hypothalamo-pituitary-adrenal (HPA) and other endocrine axes were assessed in 24 women with bulimia and healthy controls. Overnight blood samples for measuring nocturnal plasma cortisol, prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were obtained at 30-min intervals. A 1.5 mg dexamethasone suppression test (DST) and a TRH-test were performed. Patients were monitored closely while their nutritional intake was recorded over 21 days. Compared with healthy controls, nocturnal cortisol plasma levels were not elevated in the bulimics. There was a trend toward insufficient cortisol suppression in the DST in patients with bulimia, which was most pronounced in patients with signs of restricted caloric intake. Plasma dexamethasone levels were significantly reduced in bulimics compared with healthy controls. There was a trend for blunted thyrotropin stimulating hormone (TSH) responses to thyrotropin releasing hormone (TRH) in bulimia. The prolactin response to TRH was significantly reduced in bulimics with a history of anorexia nervosa. Plasma LH and plasma FSH were significantly reduced in bulimics with signs of reduced caloric intake [low T3, high levels of beta-hydroxy-butyric acid (BHBA), reduced daily caloric intake, high number of fasting days] as compared with healthy controls. Bulimics with high BHBA levels had significantly reduced nocturnal prolactin plasma levels. Results show that multiple neuroendocrine disturbances exist in bulimia in a milder form than in anorexia nervosa. Evidence for the impact of caloric intake on endocrine functions is presented. Endocrine dysfunctions in our bulimic sample did not show a positive association with the presence of depressive symptoms.     

The endocrine status in anorexia nervosa (author's transl)

Alterations in the secretion of iodothyronines, cortisol, testosterone and growth hormone have previously been described in anorexia nervosa. We have studied prolactin and gonadotropins secretion in 23 cases of anorexia nervosa. Prolactin secretion was normal. Modifications in gonadotropins release were observed. However they could not be always related to weight loss since amenorrhea could either precede weight loss or still be present after return of the weight to normal. In all cases, FSH release after LHRH stimulation was normal. No increase in LH levels was observed after LHRH injection when the weight was 70% below the ideal weight. With increasing weight, LH release progressively recovered and normal LHRH-induced LH release was obtained when the weight was above 90% of the ideal weight. At normal weight, the ratio of LH/FSH was normal in patients menstruating less than 3 months after the test, while the ratio was low in non-menstruating females. In conclusion, when the weight was insufficient basal levels of FSH and LH and responses after LHRH stimulation corresponded to a prepuberal stage. An increase in the LH/FSH ratio and a normal LH/FSH ratio preceeded the recovery of menstruations. In about 1/3 of the cases, such an evolution was not observed without any satisfactory explanation. Other factors than weight may be involved, especially when the amenorrhea persists after weight recovery.     

Eating disorders: implications for the 1990's

In the past decade much has been learned about the clinical features, diagnosis and understanding of people with anorexia nervosa and bulimia nervosa. In order to provide the next level of improvement in our care for these patients, our understanding of certain problems must be addressed by empirical research. Areas which require further study include the definition of high risk groups, the refinement of diagnoses, understanding factors which result in chronicity, determining the complications of chronicity and comparative evaluations of different treatments. These five areas are outlined in this article. Populations at risk for anorexia nervosa and bulimia nervosa may be those who must be thin and achieve according to career choice, those with a particular family and personal psychiatric history; obesity and chronic medical illnesses may be further risks. Improved diagnostic understanding has occurred by the differentiation of bulimic from restricting subtypes of anorexia nervosa. Further work must determine the relationship between the bulimic subtype of anorexia nervosa and bulimia in normal weight women and to further clarify the relationship between eating disorders and affective disorders. A number of factors may result in a chronic illness. These have been described on a variety of levels. The consequences of starvation in altering an individual's thinking, feeling and behaviour do play a role. It is not clear what factors at a neurochemical level contribute to this. Elevated endogenous opiates decreased noradrenergic function and decreased serotonin may be important. Information about the chronic complications is required for clinicians to understand the broad range of difficulties that may develop over time so that clinicians may use this information in planning treatment strategies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pituitary LH reserve suggests high risk of bulimia in amenorrheic women

The present study was aimed at investigating a) the risk of having bulimia in a heterogeneous population of secondary amenorrhea; b) the LH and FSH secretion under basal and stimulated conditions (GnRH challenge) according to the presence of bulimic risk in our study population; c) the clinical and endocrine factors predictive of the bulimic risk in amenorrheic women. Amenorrheic women (n=73; age: 23.1+/-4.8 yrs; BMI:20.2+/-2.2 kg/m2) filled in a self rating scale for bulimia (BITE) and were classified accordingly, as being at low risk (score <10), at medium risk (score between 10 and 24), and at high risk (score > or =25) of having bulimia. In each subject basal mean plasma LH levels were calculated over one hour, sampling every 10 minutes, while in a subgroup of 45 patients the area under the curve (AUC) of plasma LH and FSH levels following a challenge with two doses of GnRH (10+10 microg, every two hours), sampling every 15 minutes, was also evaluated. High risk of bulimia was present in 12.3% of the population whereas 45.2% showed a low risk and 42.5% were at medium risk of developing the disorder. Mann-Whitney U test revealed that basal LH values were differently distributed with significantly lower levels (P<0.046) in amenorrheic women at high risk of bulimia in comparison with amenorrheic women at low risk. The AUC of LH secretion following the first challenge of GnRH was significantly higher in amenorrheic women with a high risk of bulimia in respect with both groups of women at low (P<0.034) and medium (P<0.009) risk. A similar result was found with FSH AUC following the first GnRH challenge (P<0.04 high risk vs low risk and P<0.014 high risk vs medium risk). In a multiple regression analysis, the best model predicting the risk of bulimia (BITE total score) included both the LH response to GnRH challenge and BMI. In conclusion, when facing secondary amenorrhea at first consultation, long before a precise pathophysiologic diagnosis of the disease, low basal plasma LH levels and LH response to GnRH challenge may allow one to suspect the presence of abnormal eating pattern of bulimic type.     

Structural brain abnormalities in patients with bulimia nervosa

Computed tomographic (CT) brain scans were performed in 50 inpatients with bulimia nervosa, 50 anorectic inpatients, and 50 age-matched control subjects. A number of patients with bulimia nervosa had enlarged ventricles and/or sulcal widening, but the degree and frequency of ventricular dilatation and sulcal widening were not so pronounced as in patients with anorexia nervosa. As the bulimic patients were of normal body weight, the CT abnormalities cannot be attributed to emaciation, which has often been suggested as the cause of abnormalities found in anorectic patients. Since many bulimic patients repeatedly attempt to lose weight by going on restrictive diets, the morphological brain alterations may reflect the endocrine and metabolic reactions to starvation--regardless of whether starvation has led to emaciation, as in the case of anorexia nervosa, or only counterbalanced the binges of high-caloric food. This assumption is supported by the finding that in both bulimic and anorectic patients ventricular size is inversely correlated with the plasma levels of triiodothyronine, a low concentration of which is an indicator for starvation.     

The eating disorders spectrum of DSM-III-R. Clinical features and psychosocial concomitants of 86 consecutive cases from a Swedish urban catchment area.

The diagnostic spectrum of eating disorders according to DSM-III-R was examined in a sample of 86 consecutive cases from a defined urban catchment area of Stockholm, Sweden. Presenting diagnoses were: bulimia nervosa 65%; atypical eating disorders, 20%; anorexia nervosa, restricting subtype, 9%; and, anorexia nervosa, bulimic subtype, 6%. All groups showed an extreme fear of weight gain. Restricting anorexics were older, had the latest age of onset of eating disorder, and had the shortest duration of illness. Bulimic anorexics had the longest duration of illness, earliest age of onset, and greater eating disorder psychopathology than restricting anorexics and atypicals. Bulimics exhibited significantly greater eating disorder psychopathology compared with atypicals. Both bulimics and bulimic anorexics presented with significantly greater general psychopathology compared with restricting anorexics and atypicals. Atypicals appeared to be the least disturbed group, whereas bulimic anorexics were the most disturbed. Results are discussed in terms of the relative merits of DSM-III and DSM-III-R, the characteristics of particular disorders, and the possibility of an underlying sequential course of illness in the eating disorders.     

Lower serum activity of prolyl endopeptidase in anorexia and bulimia nervosa

The aim of this study was to examine whether anorexia and bulimia nervosa are accompanied by lower serum activity of prolyl endopeptidase (PEP;EC 3.4.21.26; post-proline cleaving enzyme), a cytosolic endopeptidase which cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass. Substrates of PEP are, amongst others, neuroactive peptides, such as arginine vasopressin, luteinizing hormone-releasing hormone, thyrotropin releasing hormone,alpha-melanocyte secreting hormone, substance P, oxytocin, bradykinin, neurotensin and angiotensin (Ag) I and II. Serum PEP activity was measured in the serum of 18 normal women, 21 anorexia nervosa and 21 bulimia nervosa women by means of a fluoremetric method. The Bulimic Investigatory Test, Edinburgh (BITE), the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale (HDRS) were scored. Serum PEP activity was significantly lower in patients with bulimia nervosa and anorexia nervosa, irrespective of the restricted or binging subtype, than in normal controls. There were significant and inverse correlations between serum PEP activity and the HDRS and BITE. In anorectic patients, but not in normal or bulimic patients, there was a significant correlation between serum PEP and body mass index. In bulimic patients, but not in normal or anorectic patients, there was a significant correlation between serum PEP and duration of illness. It is concluded that lowered serum PEP activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesized that a combined dysregulation of PEP and neuroactive peptides, which are substrates of PEP, could be an integral component of eating disorders.     

A taxometric investigation of the latent structure of eating disorders

The present study examined the latent structure of eating disorder symptoms in a large sample of patients with a diagnosis of anorexia nervosa restricting type, anorexia nervosa binge eating/purging type, and bulimia nervosa (n=3747). Three taxometric procedures (MAXimum EIGenvalue (MAXEIG), Mean Above Minus Below A (MAMBAC), and Latent-Mode Factor Analysis (L-Mode)) were applied to self-reported symptoms of bulimia, drive for thinness, body dissatisfaction, as well as body mass index. Taxometric analysis among patients with the restricting and binge eating/purging subtype of anorexia and those with bulimia nervosa supported a dimensional latent structure of eating disorder symptoms. Taxometric analysis also revealed a dimensional latent structure of eating disorder symptoms among patients with the restricting and binge eating/purging subtype of anorexia suggesting that the two anorexia subtypes may not represent discrete categories. These findings suggest that the diagnosis and assessment of eating disorder symptoms should be conceptualized from a dimensional framework.     

Gastrointestinal disturbances in eating disorders: clinical and neurobiological aspects

Symptoms of the upper and lower gastrointestinal (gastrointestinal) tract have been described in anorexia nervosa and bulimia nervosa. Studies focusing on general outcome and medical comorbidity describe a worse outcome in the binge eating/purging subtype of anorexia nervosa compared to the restricting subtype. Both anorexia nervosa subtypes experience substantial delays in gastric emptying as well as constipation. These gastrointestinal disturbances may play a role in anorexia nervosa patients' difficulties with refeeding and weight restoration. Bulimia nervosa patients showed increased gastric emptying capacity, with delayed gastric emptying and diminished gastric relaxation. In addition, diminished release of cholecystokinin and abnormalities in enteric autonomic function were found in bulimia nervosa patients. These factors may play a role in the perpetuation of the disease. Gastrointestinal disturbances develop secondary to the disordered eating behaviour and the concomitant malnutrition and subside mostly with the resumption of normal food intake and body weight. Knowledge of these changes may be of critical importance in avoiding misdiagnosis and successful therapy.     

Les troubles des conduites alimentaires : évaluation des troubles obsessionnels compulsifs et leur influence sur l’expression clinique des troubles

To estimate the prevalence of obsessive-compulsive disorder (OCD) in patients with eating disorders, the difference of prevalence of OCD and the distribution of autogenous and reactive obsessions according to the subtype of eating disorder (ED) and the degree of intensity of ED according the presence or not of OCD, 10 patients with restricting anorexia nervosa, 19 with bulimia nervosa and 14 with obsessive-compulsive disorder were assessed. The results showed that the prevalence was higher in bulimic patients than in anorexic patients, which is in accordance with most international studies. On the other hand, this research revealed a different distribution of autogenous and reactive obsessions in these patients, and a particular correlation between the presence of OCD and the intensity of the eating disorders.     

The course and outcome of bulimia nervosa

We reviewed the literature on the course and outcome of bulimia nervosa. Longer-term outcome is associated with a considerable degree of relapse and chronification. Diagnostic crossover to anorexia nervosa and binge eating disorder is low. Mortality in bulimia nervosa is considerably lower than in anorexia nervosa. Social adjustment and sexuality apparently normalizes in quite a few bulimic women over the course of time. A large group of bulimic patients, however, chronifies and suffers from severe bulimic symptoms and social and sexual impairment. Assessments using more systematic categories and standardized reporting procedures are required in order to make the results of studies comparable and to allow generalized conclusions.     

Temperament and character of Japanese eating disorder patients

Previous studies consistently reported a link between bulimic behaviors and high Novelty Seeking (NS), as measured by the Temperament and Character Inventory (TCI). However, it remains unclear whether this relationship is universal and occurs in different environments. Subjects of the present study consisted of 66 patients with anorexia nervosa restricting type (AN-R), 59 patients with anorexia nervosa binge eating/ purging type (AN-BP), 101 patients with bulimia nervosa purging type (BN), and 75 controls. NS score in AN-R patients was significantly lower than that in controls, although NS in BN patients did not differ from that in controls. The temperament of AN-R patients seems to be universal, even in different environments. Conversely, something other than temperament might be important in the development of bulimia nervosa in Japan.     

Pre-menarchal bulimia nervosa.

Although pre-pubertal anorexia nervosa has been well described, pre-pubertal bulimic behaviour in the context of this disorder appears to be uncommon. There have been no published reports of pre-pubertal bulimia nervosa occurring independently. Of 323 patients with bulimia nervosa attending an eating disorders research clinic between 1980 and 1989, the authors identified six patients who described pre-menarchal binge eating in the absence of a concurrent history of anorexia nervosa or massive obesity. Three (0.93%) of these patients described a pre-menarchal onset of bulimia nervosa, but there was no evidence that they were pre-pubertal. The implications of these findings are discussed.