Abnormal serum prolactin responses to luteinizing hormone-releasing hormone (LHRH) in patients with anorexia nervosa and bulimia

Abnormal responses of serum prolactin (PRL) to luteinizing hormone-releasing hormone (LHRH) stimulation have been observed in anovulatory women and in hypogonadal patients. Various endocrinological abnormalities have been demonstrated in patients with anorexia nervosa (AN). The present study was undertaken to further investigate responses of serum PRL, growth hormone (GH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) to LHRH stimulation in 65 patients with AN and in 12 patients with bulimia before therapy and in the AN patients after several months of treatment, and in comparison to 12 normal women of the same age. Serum PRL responses to LHRH were positive (peak PRL levels greater than 25 ng/ml and delta increase in PRL greater than 10 ng/ml) in 16.9% of AN and 16.6% of bulimic patients; they were negative (absent) in all controls. Following restoration of the AN patients to normal body weight, the PRL responses to LHRH became normalized in those patients whose eating disorder behavior also returned to normal. However, in those patients whose eating disorder patterns continued to be abnormal, abnormal PRL responses persisted. The bulimic patients were of normal body weight, and yet had abnormal PRL responses. Thus, the responses of PRL correlated more closely with the behavior of the underlying eating disorder rather than with body weight gain or normal body weight.     

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.     

Serum thyrotropin (TSH) responses to thyrotropin-releasing hormone (TRH) in patients with anorexia nervosa and bulimia: influence of changes in body weight and eating disorders

Serum thyrotropin (TSH) responses to thyrotropin-releasing hormone (TRH) were studied in 47 women with anorexia nervosa (AN) (group I) and in 11 bulimic patients of normal weight (group II). In group I, TSH responses were low in nine patients, delayed in 32 and normal in six. Patients with a normal TSH response had a lesser degree of anorexia than those with a delayed TSH response. Bulimia and vomiting were more frequently observed in the low response group. The maximum increase in TSH concentrations following TRH administration in the group I patients with vomiting (4.0 +/- 0.90 microU/ml, mean +/- S.E.) was significantly lower than that in the group I patients without vomiting or in normal controls (11.2 +/- 0.82 microU/ml and 11.1 +/- 2.34 microU/ml, respectively). Twenty-five patients with abnormal TSH responses in group I were retested after weight gain. Initially, TSH responses were low in six and delayed in 19. Following weight recovery, responses continued to be abnormal in five of the six and in eight of the 19, respectively. The symptoms of eating disorders continued in all patients with abnormal TSH responses even after weight recovery, whereas patients with normal responses after weight gain recovered from all symptoms. Of 11 patients in group II, six had abnormal TSH responses to TRH; the responses were delayed in four and low in two. Patients with normal responses had a lesser degree of eating disorder, compared with abnormal responders. These observations suggest that abnormal TSH responses in patients with AN were not necessarily due to weight loss alone; rather, they may be related to the eating disorder itself.     

Neuroendocrine responses to m-chlorophenylpiperazine and L-tryptophan in bulimia.

Preclinical and clinical evidence supports a theory of serotonin (5-hydroxytryptamine [5-HT]) dysregulation in bulimia. We therefore studied the prolactin (PRL) and cortisol responses following challenges with the postsynaptic 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg orally, the 5-HT precursor L-tryptophan, 100 mg/kg intravenously, and placebo in a group of 28 normal weight bulimic patients and 16 healthy controls. Patients with bulimia, regardless of the presence of major depression, had significantly blunted PRL responses following m-CPP administration compared with those in controls. In contrast, only bulimic patients with concurrent major depression had significantly blunted PRL responses following L-tryptophan administration compared with those in nondepressed bulimic patients and controls. Cortisol responses following m-CPP were not significantly different for bulimic patients vs controls, although there was a trend toward blunted cortisol responses following L-tryptophan administration in the depressed bulimic patients. These differences in neuroendocrine responses were not related to differences in age, percent of average body weight, medications, time of day, peak plasma drug levels, or baseline estradiol levels. Seasonal variations in PRL responses to both agents were identified, although covariation for season did not alter the group differences. The PRL responses following m-CPP administration were inversely correlated to baseline cortisol levels in the bulimic patients, but not in the controls, suggesting a dampening effect by hypothalamic-pituitary-adrenal axis dysfunction on postsynaptic 5-HT receptor sensitivity. The reasons for the differing hormonal responses to these two serotonergic agents may relate to differential involvement of presynaptic and postsynaptic mechanisms, 5-HT receptor subtypes, and anatomical loci of action. The blunted PRL responses to m-CPP administration suggest that postsynaptic 5-HT receptor sensitivity is altered in bulimia nervosa, and that similar alterations in 5-HT receptors at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms.     

Body Image Changes in Adolescents II Comparison among Patients with Eating Disorders and Controls with Thin, Normal and Obese Body Shapes

Abstract: The Self-Rating Body Image (SRBI) test was used to determine whether the patients with eating disorders such as anorexia nervosa or bulimia showed their body image disturbance or not. The SRBI was completed by 120 subjects who consisted of 30 low weight (LW) controls, 30 normal weight (NW) controls, 30 high weight (HW) controls, 18 anorexic patients (AN) and 12 bulimic patients (BN). The AN group had a significantly greater dissatisfaction with the scales of the body shape, visceral organ and face image of the SRBI than the weight-matched LW group. The BN group had a significantly greater dissatisfaction with the visceral organ image than the weight-matched NW group. However, no significant difference in the body shape and face images between the BN and NW groups was found. Our results suggest that the anorexic patients may disturb more parts of the body image than the bulimic patients though both the anorexic and bulimic patients showed the disturbance of body image.     

Anorexia nervosa. Treatment efficacy of cyproheptadine and amitriptyline

Patients with anorexia nervosa have concurrent problems of emaciation and depression. Therefore, treatment with medications affecting both weight gain and depression seemed reasonable. Seventy-two anorectic patients were randomly assigned in a double-blind study to receive cyproheptadine hydrochloride, a weight-inducing drug, amitriptyline hydrochloride, a tricyclic antidepressant, or placebo. Overall, cyproheptadine had a marginal effect on decreasing the number of days necessary to achieve a normal weight. There was a differential drug effect present in the bulimic subgroups of the anorectic patients: cyproheptadine significantly increased treatment efficiency for the nonbulimic patients and significantly impaired treatment efficiency for the bulimic patients when compared with the amitriptyline- and placebo-treated groups. The differential cyproheptadine effect on the anorectic bulimic subgroups is the first pharmacologic evidence of the validity of these subgroups. Cyproheptadine had an anti-depressant effect demonstrated by a significant decrease in the Hamilton depression ratings.     

Relationship of clinical factors to caloric requirements in subtypes of eating disorders

Caloric requirements for weight gain in subgroups of anorectic patients (anorectic restrictors, anorectic binge-purgers) and weight maintenance in subgroups of anorectic and bulimic patients (bulimics with and without a prior history of anorexia nervosa) were studied in a total of 36 patients. No significant differences were found between subgroups of anorectic patients either in calories to gain weight or to maintain a normal weight. Bulimic patients, as a group, were found to require significantly fewer [corrected] calories than the group of anorectic patients to maintain a normal weight. Bulimic patients with a prior history of anorexia nervosa were found to require more calories for weight maintenance than bulimics with no such prior history. In the entire eating disorder population, there was a significant negative correlation between highest premorbid body mass index (BMI) and calories required to maintain weight. These findings suggest that differences in energy metabolism may be present in the eating disorder subgroups.     

Hormone and metabolite plasma levels after oral glucose in bulimia and healthy controls

Bulimia patients claim to crave sweets and since as clinical evidence suggests that the food consumed during eating binges often contains large amounts of carbohydrates, hormones involved in carbohydrate metabolism might be affected in bulimia. We therefore performed a 4-hr glucose tolerance test (GTT), using 100 g oral glucose and inquired about attitudes toward sweets. Thirteen female patients, with a mean age of 23.3 years, who had had bulimia from 3 to 7 years but whose binge-eating/vomiting behavior was largely controlled at the time of testing, were compared to 14 age-matched healthy female controls with a mean age of 24.4 years. All bulimic patients and most controls had liked sweets as children and still liked sweets. Significantly more bulimic patients than controls stated they overate on sweets and avoided sweets. Glucose utilization and the insulin, glucagon, growth hormone (GH), and pancreatic polypeptide (PP) response curves in the bulimic patients were within the normal range. Fasting plasma levels of glucose, insulin, glucagon, GH, cortisol, free fatty acids (FFA), and PP were not different from controls. There was a trend in bulimic patients to have lower plasma FFA levels and higher plasma cortisol levels during the GTT than controls. The findings suggest that, given body weight maintenance and adequate nutrition, patients with bulimia nervosa have normal glucose tolerance and normal hormonal responses following an oral glucose load.     

Neuroendocrine aspects of primary endogenous depression VIII. Pituitary-gonadal axis activity in male patients and matched control subjects

To determine the extent of hypothalamo-pituitary-gonadal (HPG) axis dysfunction in endogenous depressed men, we measured nocturnal and diurnal serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), and estradiol (E2) concentrations, and their responses to gonadotropin releasing hormone (LHRH) and dexamethasone administration, in 16 Research Diagnostic Criteria primary, definite endogenous male depressives and 16 individually matched male normal controls. Compared to their controls, the patients showed no differences in basal nocturnal or diurnal gonadotropin or gonadal steroid hormone concentrations, and no differences in hormone concentrations either post-LHRH or post-dexamethasone. Age was negatively correlated with baseline serum T in the patients but not in the controls, and it was modestly positively correlated with baseline serum LH in both groups of subjects. In the patients, the presence of DSM-III melancholia was modestly negatively correlated with baseline and post-LHRH concentrations of both LH and FSH and was positively correlated with baseline serum T, but it bore no relation to serum E2. None of the other subject characteristics or specific dimensions of depressive symptomatology were significantly related to the HPG axis measures. The HPG axis measures also were unrelated to pre- and post-dexamethasone cortisol concentrations in both groups of subjects. The results of this study suggest that, in contrast to the hypothalamo-pituitary-adrenal cortical and thyroid axis abnormalities frequently found in endogenous depressives, HPG axis function in male depressives is relatively normal.     

Altered norepinephrine regulation in bulimia: effects of pharmacological challenge with isoproterenol

While abnormalities in central norepinephrine regulation may contribute to abnormal eating patterns in bulimia nervosa, alterations in function of the peripheral sympathetic nervous system could contribute to the decreased metabolic rate and increased anxiety responses previously reported in these patients. To assess beta-adrenergic receptor sensitivity in bulimic patients, we studied cardiovascular and hormonal responses to acute pharmacological challenge with intravenously administered isoproterenol. In comparison to healthy controls, binge-abstinent bulimic patients had significantly reduced mean baseline plasma norepinephrine level, pulse rate, and systolic blood pressure, and significantly increased chronotropic responses to isoproterenol infusion. Decreased sympathoneural activity may contribute to a tendency for bulimic patients to maintain body weight despite low caloric intake.     

Cytokine mRNA expression patterns in the disease course of female adolescents with anorexia nervosa

Anorexia nervosa (AN) is a serious eating disorder characterized by extreme weight loss and abnormalities of the neuroendocrine and immune systems. Cytokines have been discussed to be involved in the pathomechanisms underlying cachexia. Therefore our study aimed at examining the mRNA expression pattern of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6) and interleukin-10 (IL-10) in whole blood of 11 female AN patients and 10 age and sex matched normal weight control subjects using a sensitive quantitative polymerase chain reaction (PCR) method. We found a significant increase in TNF-alpha and IL-6 mRNA expression in anorectic patients at admission (mean BMI 14.8 +/- 1.3) when compared to controls. During follow-up, the expression of TNF-alpha mRNA remained significantly higher in formerly anorectic patients (mean BMI 18.7 +/- 0.5) while IL-6 mRNA expression decreased. We interpret our results as suggesting that TNF-alpha may contribute to metabolic abnormalities in anorexia nervosa even after goal BMI is achieved.     

Neuroendocrine regulation in depressed postmenopausal women and healthy subjects

Results from prior studies utilizing gonadotropin-releasing hormone (GnRH) in affective illness have been contradictory. There have been no systematic investigations of multiple pituitary hormonal responses to GnRH infusion in either depressed or healthy postmenopausal women. Potential abnormalities in the hypothalamic-pituitary-gonadal (HPG) axis may be limited to postmenopausal women who lack the estradiol feedback influence at the pituitary level. We therefore studied 18 depressed and nine healthy postmenopausal women with the GnRH infusion test and measured LH, FSH, prolactin, growth hormone, and thyrotropin responses. Our findings confirmed earlier reports of a lower basal LH concentration in postmenopausal depressed subjects. GnRH stimulated release of LH, FSH, and prolactin in both patients and controls; however, there were no differences in the mean peak hormone values between groups.     

Luteinizing hormone and cortisol responses to naloxone in normal weight women with bulimia

The present study was undertaken in order to establish whether alterations in the endogenous opioid control of luteinizing hormone (LH) and ACTH/cortisol secretion occur in bulimic women with normal body weight and normal menstrual cycles. For this purpose, the capability of the opioid antagonist naloxone (4 mg injected as an intravenous bolus at time 0, plus 10 mg infused over 2 hr) to increase the circulating levels of LH and cortisol was tested in nine bulimic women and in nine age- and weight-matched normal controls. All women were tested on the 22nd day of a normal menstrual cycle. Two days later, a control test with normal saline (NaCl 0.9%) instead of naloxone was performed. The basal levels of LH and cortisol were similar in the bulimic and normal subjects and were not modified by the administration of normal saline. In contrast, the administration of naloxone significantly increased plasma LH and cortisol levels in all subjects, with peak LH responses at 30 min and peak cortisol responses at 60 min. The naloxone-induced LH and cortisol increases were significantly higher in the bulimic women than in the normal controls. These data indicate the presence of an increased opioid inhibitory tone in the control of LH and ACTH/cortisol secretion in normal weight bulimic women with normal menstrual cycles.     

Emotional eating in anorexia nervosa and bulimia nervosa

ObjectivesThe relationship between emotional states and eating behaviors is complex, and emotional eating has been identified as a possible factor triggering binge eating in bulimia nervosa (BN) and binge eating disorder. Few studies considered emotional eating in patients with anorexia nervosa.MethodsThe present study evaluated the clinical correlates of emotional eating in 251 eating-disordered (EDs) subjects (70 AN restricting type, 71 AN binge eating/purging type, 110 BN purging type) and in a group of 89 healthy control subjects. Subjects were assessed by means of a clinical interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and several self-reported questionnaires, including the Emotional Eating Scale (EES).ResultsNo significant differences were found between the 3 EDs groups in terms of EES total score, and all patients with ED showed higher EES scores compared with control subjects. Emotional eating was associated with subjective binge eating in AN binge eating/purging type and with objective binge eating in patients with BN. Among patients with AN restricting type, emotional eating was associated with restraint, but this association was lost when controlling for fear of loss of control over eating, which was the principal determinant of restraint.ConclusionEmotional eating and fear of loss of control over eating are significantly associated with specific eating attitudes and behaviors, according to the different diagnoses. Emotional eating is a relevant psychopathologic dimension that deserves a careful investigation in both anorectic and bulimic patients.     

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.     

Pancreatic B-cell functioning after intravenous glucagon administration in anorexia nervosa.

Abnormal glucose tolerance is often found in patients with anorexia nervosa (AN). We attempted to evaluate pancreatic B-cell functioning after intravenous glucagon administration. Fourteen patients with the restricting type of AN (percentage of ideal body weight 71.5 +/- 1.6%, mean +/- SE) and 6 patients with the bulimic type of AN (77.0 +/- 3.0%) were studied. After an overnight fast, glucagon (0.02 mg/kg) was injected i.v. into all subjects and 6 normal controls. Blood samples were obtained at 0, 5, 30, 60, 90 and 120 min to measure blood glucose (BS), serum insulin (IRI) and C-peptide (CPR). The same tests were repeated in 8 patients with restricting AN after therapy and restoration of body weight (85.9 +/- 1.0% of ideal body weight). BS responses did not differ among the groups. Peak serum levels (5 min) of both IRI and CPR in restricting AN patients were significantly lower than those in bulimic AN patients and in normal controls. BS, IRI and CPR concentrations did not change significantly following restoration of body weight. Pancreatic B-cell dysfunction after glucagon administration was observed in restricting AN patients and the abnormality persisted after short-term weight restoration.     

Altered cerebrospinal fluid neuropeptide Y and peptide YY immunoreactivity in anorexia and bulimia nervosa

The related central nervous system peptides neuropeptide Y and peptide YY have been found to be among the most potent endogenous stimulants of feeding behavior. We measured these neuropeptides in cerebrospinal fluid to determine whether they contributed to the pathophysiologic characteristics of anorexia and bulimia nervosa. Cerebrospinal fluid neuropeptide Y concentrations were significantly elevated in underweight anorectic patients and in many of the anorectic patients studied at intervals after weight restoration. These levels normalized in long-term weight-restored anorectic patients who had a return of normal menstrual cycles. Increased neuropeptide Y activity may contribute to several characteristic disturbances in anorexia, including menstrual dysregulation. Cerebrospinal fluid peptide YY concentrations were significantly elevated in normal-weight bulimic patients abstinent from pathological eating behavior for a month compared with themselves when actively bingeing and vomiting or compared with healthy volunteers. Increased peptide YY activity may contribute to a drive to overfeed in normal-weight bulimic patients.     

Prevalence of eating disorders and eating attacks in narcolepsy

Narcoleptic patients suffer frequently from obesity and type II diabetes. Most patients show a deficit in the energy balance regulating orexinergic system. Nevertheless, it is not known, why narcoleptic patients tend to be obese. We examined 116 narcoleptic patients and 80 controls with the structured interview for anorectic and bulimic eating disorders (SIAB) to test the hypothesis that typical or atypical eating attacks or eating disorders may be more frequent in narcoleptic patients. No difference in the current prevalence of eating disorders bulimia nervosa, binge eating disorder, or anorexia nervosa was found, nor was the frequency of eating attacks higher in the narcolepsy group. We conclude that present eating disorders and eating attacks as defined in DSM IV are not the reason for the observed differences in body composition. Additional factors, such as basal metabolic rates and lifestyle factors need to be considered.     

Hormonal circadian rhythms in eating disorders

The circadian rhythm of several plasma hormones (prolactin, growth hormone, adrenocorticotropic hormone (ACTH), cortisol, and melatonin) was simultaneously evaluated in 23 women with anorexia nervosa (AN), in 27 obese (OB) women, and in gender and age-matched healthy controls. A trend toward similar alterations of the circadian pattern of the different hormones was observed in the two groups of patients, with the exception of plasma growth hormone (GH), which exhibited nutrition-dependent impairments. The timing of the peaks for each hormonal rhythm revealed the existence of an internal desynchronization in both eating disorders.     

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis in male depressive disorders – A systematic review and meta-analysis

Sexual dysfunctions are common in men with depression. As the hypothalamic-pituitary-gonadal (HPG) axis is a crucial regulator of sexual function, and also affects mood and cognition, the following question arises: Is the HPG axis altered in depressed men when compared to healthy controls?To answer this question, PubMed and PsycINFO were searched. Inclusion criteria for the systematic review and meta-analysis were: (1) case-control study including male patients with a depressive disorder and (2) assessment of follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, or testosterone.Seventeen studies were identified. Follicle-stimulating hormone and LH did not differ between patients and controls. By contrast, in patients, oestradiol was marginally increased (g = 0.52, 95% CI [−0.01, 1.04]; Z = 1.92, p = .055) and testosterone was significantly decreased (g = −0.45, 95% CI [−0.80, −0.10]; Z = −2.53, p = .012).Depressed men may be characterised by diminished testosterone and potentially elevated oestradiol, which beyond contributing to sexual dysfunction, could impact mood and cognition.