Neuroendocrine profile in bulimia nervosa

The neuroendocrinology of bulimia nervosa has only recently been investigated, with initial research suggesting some biological overlap with both anorexia nervosa (AN) and depression. Similarities among AN, depression, and bulimia include a nonsuppressed Dexamethasone Suppression Test and an abnormal growth hormone (GH) response to thyrotropin-releasing hormone (TRH). Bulimics and anorectics both tend to have a delayed thyrotropin (TSH) response to TRH and elevated basal GH levels. Bulimics, however, have a normal GH response to clonidine, a nonblunted TSH response to TRH, low basal prolactin (PRL) levels, and may have an exaggerated PRL response to TRH. Unpublished data suggest bulimics may have a gonadotropin profile distinct from either AN or depression, as well as a variety of other endocrinopathies. Although many of these abnormalities may reflect malnutrition despite normal weight, other factors that are as yet unidentified are likely to be contributing to the neuroendocrine abnormalities seen in bulimia.     

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.     

Gonadotropin response to LH-RH in anorexia nervosa and bulimia

Serum LH and FSH levels before and after stimulation with LH-RH were measured in 9 patients with bulimia, 7 with a restricting subtype and 6 with a bulimic subtype of anorexia nervosa. All patients with anorexia nervosa and 5 (56%) patients with bulimia showed amenorrhea for at least 5 months, while 4 (44%) of the bulimic patients showed oligomenorrhea. Mean basal levels of LH and FSH were low in patients with restricting and bulimic anorexia nervosa, but were normal in patients with bulimia. The response of LH and FSH to LH-RH was impaired in approximately half of the patients with the two subtypes of anorexia nervosa, whereas it was normal in all but one patient with bulimia. These results suggest that bulimic patients with amenorrhea or oligomenorrhea have hypothalamic dysfunctions, which do not appear to be due solely to low weight or to metabolic changes resulting from binge eating, vomiting or purgative use.     

Studies of growth hormone (GH), thyrotropin (TSH) and prolactin (PRL) secretion in anorexia nervosa.

(1) Studies of serum thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) responses following TRH administration were performed in 7 subjects with anorexia nervosa (AN). (2) Five patients demonstratod significant increases in circulating GH from a mean of 15.6 ng/ml to a peak of 31.8 ng/ml 30 min after TRH. (3) Basal TSH concentrations were undetectable (< 2μU/ml) in all patients prior to stimulation but following TRH, significant elevations (ΔTSH > 6 μU/ml) in TSH were identified in 3/7 patients. (4) The largest elevations in TSH occurred in the two subjects in whom no GH rises were found, whereas blunted TSH rises were noted in 4/5 subjects who showed substantial GH secretory responses to TRH. (5) Basal PRL concentrations were normal and rose appropriately after TRH in all subjects. (6) These studies demonstrate that GH secretion can be provoked in AN by TRH similar to patterns in other states (acromegaly, uremia, protein-calorie malnutrition), characterized by elevated basal GH concentrations. (7) It is hypothesized that activated GH secretion may favor TRH responsivity of somatotrophs. (8) Obtundation of TSH secretion in AN, moreover, may be related to the augmented secretion of GH, since TSH secretion can be lowered by exogenous GH administration in man.     

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.     

Abnormal growth hormone release following luteinizing hormone releasing hormone in anorexia nervosa

We studied the luteinizing hormone (LH), follicle stimulating hormone (FSH) and growth hormone (GH) secretion following an i.v. injection of 0.1 mg of luteinizing hormone releasing hormone (LHRH) in patients with anorexia nervosa, who showed the GH secretion after thyrotropin releasing hormone (TRH). Five out of 11 patients had an elevated plasma GH level in a fasting state. The administration of LHRH resulted in a significant increase in the plasma GH concentrations in 3 of the 11 patients. Three other patients also showed an elevation of the plasma GH concentration to 7.0, 18.4 and 29.6 ng/ml, which were 212, 175 and 191% of the preinjection levels, respectively. There is a positive correlation between the basal and peak plasma GH levels after LHRH. These increases, however, were related to neither the plasma gonadotropin responses to LHRH nor the plasma GH responses to TRH. The basal levels of plasma LH were reduced in 8 patients and normal responses to LHRH were observed in only one patient. Although plasma FSH was undetectable in 5 patients, the FSH response to LHRH appeared normal in 9 patients. These results indicate that an elevation of the plasma GH level after LHRH is not confined to patients with a GH secreting pituitary tumor but observed in subjects with anorexia nervosa and further suggest that the GH responsiveness to non-specific hypothalamic releasing hormones may be due to the impaired hypothalamic control in anorexia nervosa.     

Triiodothyronine administration reduces serum growth hormone levels and growth hormone responses to thyrotropin-releasing hormone in patients with anorexia nervosa

The aim of this study was to test the hypothesis that low serum T3 concentrations may promote an abnormal growth hormone (GH) response to thyrotropin-releasing hormone (TRH) in patients with anorexia nervosa. Eight anorexic women and two anorexic men, ages 15-25 years, with low free T3 circulating levels (mean +/- SEM = 2.8 +/- 0.3 pmol/l) were studied. A TRH test (200 micrograms IV) was carried out under basal conditions and repeated following treatment with oral T3 (1.5 micrograms/kg BW/day) for eight days. Following T3 administration, GH levels dropped significantly from a baseline of 7.1 +/- 1.3 micrograms/l to 3.1 +/- 0.7 micrograms/l (p less than 0.02), as did GH peak responses to TRH (9.0 +/- 1.0 micrograms/l vs 4.4 +/- 0.8 micrograms/l, p less than 0.01). ANOVA and analysis of area under the curve (AUC) confirmed that after T3 treatment there was a significant reduction in TRH-induced GH release in these patients (GH AUC: 902 +/- 132 micrograms/l vs. 456 +/- 91 micrograms/l, p less than 0.02). TSH responses to TRH, which were normal prior to T3 treatment, completely disappeared following it, and PRL responses to TRH also were diminished. Although our experimental approach does not permit a conclusion that low T3 levels were the primary reason for these changes, the data support the theory that low T3 circulating levels may facilitate abnormal GH secretion and the GH-releasing activity of intravenous TRH.     

CSF somatostatin in anorexia nervosa and bulimia: relationship to the hypothalamic pituitary-adrenal cortical axis

The eating disorders, anorexia nervosa and normal weight bulimia, are associated with disturbances of hypothalamic-pituitary-adrenal cortical (HPA) and growth hormone function. Because somatostatin (SRIF) is one of the neuropeptides known to modulate feeding behavior and neuroendocrine systems, we measured cerebrospinal fluid (CSF) concentrations of this peptide in patients with eating disorders. CSF SRIF concentrations in patients with anorexia nervosa, both at low weight and after weight recovery, were similar to those in controls. When normal weight bulimic women stopped binging, they had a modest but significant increase in CSF SRIF. CSF SRIF was not related to plasma growth hormone concentrations but did show relationships to HPA axis hormones. Healthy volunteer women had a significant positive relationship between CSF SRIF and CSF corticotropin releasing hormone (CRH). In underweight anorectics, CSF SRIF was negatively related to both 24-hr urinary free cortisol and plasma cortisol concentrations after dexamethasone, but it was not significantly related to CSF CRH. These relationships more closely resembled those of healthy controls after weight correction. In bulimics, CSF SRIF was positively related to CSF CRH and negatively related to plasma cortisol. Our findings support a previously described relationship between CSF SRIF and HPA axis activity. The differences in SRIF-HPA relationships in anorectics and bulimics may constitute or reflect pathophysiological distinctions between these disorders.     

Abnormal growth hormone and cortisol, but not thyroid-stimulating hormone, responses to an intravenous glucose tolerance test in normal-weight, bulimic women

Abnormal growth hormone (GH) and adrenocorticotropic hormone (ACTH)/cortisol secretory patterns in response to a glucose load have been observed in underweight anorectic women. The present study was performed in an attempt to establish whether changes in the hypothalamic/pituitary sensitivity to hyperglycemia occur in bulimia in the absence of weight disturbance. Therefore, serum GH, plasma cortisol, and plasma insulin concentrations were measured in eight women with normal weight bulimia and in eight normal women during an intravenous glucose (0.33 g/kg as an bolus) tolerance test (IGTT). In addition, since abnormal pituitary hormone responses to a glucose load might reflect alterations in somatostatin (SRIH) release, TSH secretion also was measured, in view of its sensitivity to SRIH inhibition.

Both GH and cortisol levels progressively and significantly declined during IGTT in the normal subjects. In the bulimic women, cortisol levels remained unchanged, whereas GH concentrations rose significantly after glucose injection. Plasma cortisol and serum GH levels were significantly higher in the bulimic than in the control subjects. No significant differences between groups were observed in hyperglycemia-induced insulin increments or in TSH decrements.

These data indicate that an altered sensitivity to hyperglycemia affects the hypothalamic/pituitary centers controlling the secretion of the counterregulatory hormones GH and ACTH/cortisol in bulimia nervosa. The lack of a simultaneous change in the TSH secretory pattern argues against a possible involvement of SRIH in the pathophysiology of this disorder.     

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.     

Delayed TSH release in anorexia nervosa following injection of thyrotropin-releasing hormone (TRH)

We studied plasma concentrations of thyrotropin (TSH), prolactin and growth hormone (GH) after injection of 500 microgram of thyrotropin-releasing hormone (TRH) in 10 patients with acute anorexia nervosa, subsequent to initial nutritional stabilization and again after weight recovery. Plasma thyroxine levels were normal throughout, whereas plasma triiodothyronine levels were low initially but rose with weight gain. The TSH secretory response to TRH was delayed and prolonged during the initial study but showed a normal overall quantitative response, except for two patients who showed no TSH rise. Following weight gain the TSH response was more rapid, and positive correlations were found between body weight and peak TSH levels and rapidity of TSH response. Six of 10 patients, however, continued to exhibit a delayed TSH peak response, the average response was markedly increased in comparison with that in normal females. The prolactin response curves were normal at both times. Rises in GH following TRH were observed in two patients prior to and in one patient after weight gain. We conclude that acute anorexia nervosa, with its concomitant profound weight loss, is accompanied by abnormalities in the hypothalamo-pituitary-thyroid axis, which are reversed only in part with improvement in the illness and weight gain, suggesting the persistence of disordered neuroendocrine function in this illness.     

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.     

Effects of antidepressant treatment on thyrotropin-releasing hormone stimulation, growth hormone response to L-DOPA, and dexamethasone suppression tests in major depressive patients

Dexamethasone suppression (DST), thyroid-stimulating hormone (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) and growth hormone (GH) response to L-DOPA tests were evaluated in 19 depressed inpatients before the commencement of the antidepressant treatment and after the clinical response to examine: (i) the functional relationships among the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis and dopaminergic system in depression, (ii) any alterations in these hormonal functions with the antidepressant treatment. TSH responses to TRH showed a tendency to increase from pre- to posttreatment period, while TRH-induced PRL and L-DOPA-induced GH responses did not change with treatment in depressed patients who responded to the treatment. Females showed significantly higher TSH and PRL responses to TRH compared to males. No interconnections were found among the responses in DST, TRH stimulation test and L-DOPA-induced GH test in the patients. The results do not support the interrelations between the abnormalities in the HPT and HPA axes and central dopaminergic activity in depression.     

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.     

Relationship of bone density to estradiol and cortisol in anorexia nervosa and bulimia

Dual photon absorptiometry was used to assess the risk of developing osteoporosis in patients with anorexia nervosa and patients of normal weight with bulimia nervosa. Anorectic patients had significantly lower vertebral bone mineral densities compared with healthy controls. Bulimic patients had values similar to those of controls, and the differences between bulimics and anorectics narrowly missed significance. No significant difference was found between patient groups in measurements of serum estradiol, but anorectics, compared with bulimics, had significantly higher values of 24-hour urinary free cortisol. Hypercortisolemia, by diminishing bone formation and increasing bone resorption, is likely to contribute to the development of osteoporosis in patients with eating disorders.     

Average total energy expenditure in anorexia nervosa, bulimia nervosa, and healthy young women

The double-labeled water method was used to measure average daily total energy expenditure (EE) in 11 healthy normal-weight women classified as unrestrained eaters, in 8 patients with anorexia nervosa, and in 8 patients with bulimia nervosa. The body mass index was 20.0 +/- 1.3 kg/m2 in the control group, 15.2 +/- 5.6 kg/m2 in the anorectic groups, and 19.7 +/- 1.9 kg/m2 in the bulimic group. EE was measured over a 2-week period during which weight remained constant in all groups and was 2357 +/- 504 kcal/day for the controls, 2510 +/- 920 kcal/day for the bulimics, and 2899 +/- 656 kcal/day for the anorectics. Differences were not significant among groups. Physical activity was recorded in diaries by all subjects. Anorectic patients showed significantly more activity than all other groups. The data suggest that EE is high in anorectic patients as a consequence of physical activity.     

Abnormal thyroid stimulating hormone, prolactin, and growth hormone responses to thyrotropin releasing hormone in abstinent alcoholic men with cerebral atrophy

The thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) responses to thyrotropin releasing hormone (TRH), the Wechsler Adult Intelligence Scale (WAIS) for cognitive impairment, and computed tomographic scans were evaluated in 15 nondepressed alcoholic men after 4 weeks of abstinence and in 10 normal controls. Both cognitive impairment and cerebral atrophy were found in 13 of the alcoholics. Eight alcoholics (seven with cerebral atrophy) had blunted TSH and PRL responses to TRH and a TRH-induced paradoxical increase of GH. This study demonstrates that besides affecting the TSH response to TRH, alcoholism often induces alterations of the PRL and GH secretory patterns in response to TRH. The severe brain damage caused by long-term alcoholism might be involved in the pathogenesis of these neuroendocrine alterations.     

TRH stimulation test in obsessive-compulsive patients

Serum thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) levels were measured before and after stimulation with 200 micrograms of thyrotropin releasing hormone (TRH) in 10 patients with obsessive-compulsive disorder (OCD) and in 10 control subjects. There were significantly more blunted TSH responses among OCD patients than control subjects. PRL and GH responses to TRH challenge did not differ between OCD patients and controls. These results may indicate dysregulation of the hypothalamic-pituitary-thyroid axis in OCD.     

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.     

Growth hormone responses to growth hormone-releasing hormone, clonidine and insulin-induced hypoglycemia in normal weight bulimic women

The growth hormone (GH) responses to GH-releasing hormone (GHRH; 1 microgram/kg BW in an i.v. bolus), clonidine (150 micrograms in a single oral dose) and insulin (0.15 IU/kg BW in an i.v. bolus) induced hypoglycemia were evaluated in 7 normal weight bulimic women with regular menstrual cycles and in 7 age- and weight-matched normal women. In addition, the effect of thyrotropin-releasing hormone (TRH; 200 micrograms in an i.v. bolus) on serum thyroid-stimulating hormone (TSH) and GH levels was measured in the same subjects. Tests were carried out in random order on the 22nd days of the following menstrual cycles. A control test with the i.v. administration of normal saline instead of drugs was carried out 2 days after the TRH test. Basal GH levels were significantly higher in bulimic women than in normal controls; despite higher GH levels, bulimic women showed normal circulating concentrations of somatomedin-C (Sm-C). Serum GH levels remained unmodified during the control test. In contrast, the administration of GHRH, clonidine or insulin induced significant GH responses in all subjects. Bulimic and normal women showed comparable responses after GHRH, clonidine or hypoglycemia. The hypoglycemic response to insulin was similar in bulimic and control subjects. The administration of TRH was unable to increase the circulating levels of GH in the normal controls, whereas it significantly increased GH concentrations in 5 of 7 bulimic women.(ABSTRACT TRUNCATED AT 250 WORDS)