Plasma, salivary, and urinary oxytocin in anorexia nervosa: a pilot study.

Although oxytocin (OT) has the potential to be an informative biomarker of social functioning in patients with eating disorders, the burden of invasive blood draws or lumbar punctures limits OT study. Salivary and urinary OT measurements may be advantageous, as they require less invasive sampling techniques which could be conducted in a wider variety of settings. Yet, the degree to which the concentration of OT in these fluids is correlated with blood levels is uncertain, as is the impact of vomiting on salivary secretion of OT. Therefore, we compared contemporaneously sampled OT concentration in blood, saliva, and urine from twenty women acutely ill with anorexia nervosa. Salivary OT was positively correlated with plasma OT in patients with no history of self-induced vomiting (r=0.89), but correlation was lower in those with recent history of self-induced vomiting (r=0.42). Urinary and plasma OT were not well-correlated(r=0.13), suggesting preliminarily that collection of plasma OT remains the method of choice. Self-induced vomiting in eating disorders may limit the applicability of salivary sampling for OT.

Steroid metabolism and excretion in severe anorexia nervosa: effects of refeeding.

BACKGROUND: To our knowledge, changes in steroid metabolism in subjects with anorexia nervosa (AN) after weight gain have not been elucidated. OBJECTIVE: We characterized urinary steroid excretion and metabolism in AN patients and investigated the effects of refeeding. DESIGN: In an intervention study, we recruited 7 women with life-threatening weight loss upon admission and after a median [interquartile range (IQR)] of 95 d (88-125 d) of intensive refeeding; 15 age-matched women were recruited as control subjects. The major urinary metabolites were quantified in 24-h collections by capillary gas chromatography. A single examiner measured weights, heights, and skinfold thicknesses. RESULTS: The median (IQR) age of patients was 24 y (21-26 y), and the duration of AN was 4.0 y (3.3-8.0 y). Body mass index (BMI; in kg/m(2)) increased from 12.8 (12.7-13.1) to 18.6 (18.0-19.6) after refeeding (P < 0.0001). Steroid values [median pre-, post-refeeding (P value)] were as follows: androgen metabolites [472, 1017 µg/24 h (0.93)], cortisol metabolites [1960, 3912 µg/24 h (0.60)], and ratios of androsterone (5α)/etiocholanolone (5ß) [0.28, 0.63 (<0.001)], 5α-/5ß-tetrahydrocortisol [0.20, 0.48 (0.02)], tetrahydrocortisols/tetrahydrocortisone [0.87, 0.61 (0.09)], 20-hydroxy-/20-oxocortisol metabolites [0.29, 0.47 (0.01)], and 20α-/20ß-reduced cortisol metabolites [1.18, 1.89 (≥1.00)]. BMI change was positively correlated with 5α-/5ß-tetrahydrocortisol (r = 0.95, P < 0.001). Before refeeding, the following metabolites were lower in patients than in control subjects: androsterone, 5α-tetrahydrocortisol, α-cortolone and α-cortol, 5α-/5ß-tetrahydrocortisol, androsterone/etiocholanolone, and 20-hydroxy/20-oxocortisol (all P < 0.05). After refeeding, all steroid metabolites in patients were at concentrations that were comparable with those in control subjects. CONCLUSIONS: Significant changes in urine steroid-metabolite excretion occurred upon starvation, which were reversed upon refeeding. For cortisol, there were decreases in 5α-/5ß-tetrahydrocortisol and 20-hydroxy-/20-oxometabolites; for androgen, there was a decrease in androsterone/etiocholanolone.

The relationship between serum levels of estradiol and osteoprotegerin in patients with anorexia nervosa.

Osteoporosis is one of the major complications in anorexia nervosa (AN) patients. Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) have been identified as important regulators of bone turnover. The objective of this study was to clarify the role of RANK-RANKL-OPG system, and their relationship with other regulators for bone metabolism in AN patients. We investigated serum levels of RANKL, OPG, and bone turnover markers of 26 Japanese young female AN patients and 7 age-matched healthy women. We measured serum levels of estradiol (E2), insulin like growth factor-I (IGF-I) and triiodothyronin (T3) from the same samples and studied their relationship with RANKL or OPG. Mean serum levels of E2, IGF-I, T3 and leptin in AN patients were significantly lower than those of controls (p<0.05). Serum levels of OPG in AN patients were significantly higher than those in controls and negatively correlated with body mass index (BMI), E2, IGF-I or leptin. Serum levels of free RANKL could not be detected except for only one healthy control in both groups. These results suggest that serum OPG levels may be increased by a compensatory mechanism for malnutrition and estrogen deficiency which induces an increase in bone resorption.

Physical activity and cortisol in anorexia nervosa.

Elevated physical activity is commonly observed among patients with Anorexia Nervosa (AN) and can manifest in several forms. While elevated physical activity may play a key role in the pathophysiology of this disorder, much remains unknown about it, including the relationship among its various manifestations, and their underlying mechanism(s). The purposes of the current study were to (1) quantify locomotor activity in inpatients with AN using an accelerometer, (2) determine the association between locomotor activity and exercise history and (3) determine the association between urinary cortisol and physical activity. Thirty-six women hospitalized with AN wore activity armbands for 48 h during the first 2 weeks of hospitalization, collected 24-h urine to measure cortisol, and completed rating forms. Activity counts varied more than four-fold among individuals but were consistent within individuals over the 2 monitoring days (p<0.001). Averaged 24-h activity counts were positively correlated with pre-hospitalization attitude towards exercise as measured by the Commitment to Exercise Scale (CES; p=0.032). Forty-two percent of women reported "high" exercise in the 3 months before hospitalization; compared to non-high-exercising patients, these women demonstrated a higher CES score (p<0.001) and a trend toward greater activity counts (p=0.059). Urinary cortisol was positively associated with activity counts (p=0.044) and CES score (p=0.018). These data suggest that some women with AN have a higher "drive" for physical activity that persists into early hospitalization. HPA axis abnormalities may be associated with this state.

The adrenal sensitivity to ACTH stimulation is preserved in anorexia nervosa.

Hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in anorexia nervosa (AN) has been demonstrated and is likely to reflect a central nervous system (CNS)-mediated effect of starvation. Alterations in the adrenal response to ACTH in AN have also been reported by some authors. In order to define the adrenal sensitivity to ACTH in this condition, we studied cortisol (F), aldosterone (A) and DHEA responses to the sequential administration of low and supramaximal ACTH 1-24 doses (0.06 microg/m2 ACTH 1-24 iv at 0 min and 250 microg ACTH 1-24 iv at +60 min, respectively) in 10 young women with AN [ANW, age 21.2 +/- 0.9 yr, body mass index (BMI) 15.7 +/- 0.6 kg/m2]. The results in this group were compared with those recorded in 10 healthy normal women (HW, 23.4 +/- 1.1 yr, 21.9 +/- 0.9 kg/m2). In ANW urinary F levels were similar to those in HW. Basal serum F, A and DHEA levels in ANW were not significantly different from those in HW. In HW the lowest ACTH dose induced a significant (p<0.05) increase of F, A and DHEA. The maximal ACTH dose induced F, A and DHEA increases greater (p<0.05) than those induced by the lowest ACTH dose. In ANW both ACTH doses induced significant (p<0.05) F and DHEA increases which were not significantly different from those in HW, though a trend toward a lower cortisol response after ACTH 0.06 microg/m2 in ANW was present. Like in HW, in ANW the maximal ACTH dose induced F and DHEA increases greater (p<0.01) than those induced by the lowest dose. Unlike HW, in ANW A levels did not increase after the lowest ACTH dose while they increased after the maximal one overlapping the response in HW. In conclusion, the cortisol and DHEA responses to a very low and a supra-maximal ACTH dose in patients with AN were similar to those in healthy subjects, indicating that the sensitivity to ACTH of the fasciculata and reticularis adrenal zones is preserved in this condition. On the other hand, a reduced sensitivity to ACTH of the glomerularis adrenal zone in patients with AN is suggested by the lack of aldosterone response to the lowest corticotropin dose.

[Bone metabolism in adolescent girls with short course of anorexia nervosa]. / Metabolizm tkanki kostnej u mlodych dziewczat z krótkim przebiegiem jadlowstretu psychicznego.

OBJECTIVE: The objective of this study was to determine the prevalence of bone mass reduction and determine its causes in young girls with short course of anorexia nervosa (AN). METHOD: Bone mineral density (BMD)of lumber spine by dual energy x-ray absorptiometry, total alkaline phosphatase (TAP), bone-Gla protein (BGP), urine deoxypyridinoline (DPYR), DPYR, urine calcium, sex hormones were measured in 24 in-patient girls with diagnosed AN and 20 healthy volunteers. RESULTS: Girls with AN had a significantly lower BMD than their age-matched controls. Osteopenia and osteoporosis were present even in the group with AN diagnosed within the previous 12 months. BMD correlated negatively with minimal BMI and positively with the duration of regular menses before AN onset. BGP and DPYR were significantly lower in AN patient than in the control group. Values of urine calcium of AN patients were comparable with control group, but showed a positive correlation with disease duration. DISCUSSION: Reduction of bone mineral density is present in girls with short course of AN. Nutritional status is the most important predictor of BMD. Bone metabolism is decreased in the early stages of the disease.

Bone resorption in anorexia nervosa and rehabilitated patients.

OBJECTIVE: To assess the impact of anorexia nervosa and that of nutritional rehabilitation on bone resorption. DESIGN: Cross-sectional, observational study. SETTING: Rome, Italy SUBJECTS: Twenty-eight female patients affected by anorexia nervosa (AN, BMIor=18.5 kg/m(2)) and 34 age- and sex-matched healthy controls (CO, BMI >or=18.5 kg/m(2)). Among AN patients, 16 were affected by the 'restrictive' (ANr) and 12 by the 'purging' type (ANp) of anorexia nervosa. METHOD: Body weight, height and skeletal diameters were measured on each individual. The skeletal mass (SKM) was predicted from the skeletal diameters of the elbow, wrist, knee and ankle, using the equation of Martin. Twenty-four-hour urinary excretion of pyridinium crosslinks of collagen (pyridinoline (Pyd) and deoxypyridinoline (Dpd)) and creatinine was assessed by reversed-phase HPLC with fluorimetric detection after solid-phase extraction and by the Jaffé-method with deproteinization, respectively. RESULTS: Twenty-four-hour urinary output of Pyd and Dpd was not significantly different between AN and CO when expressed in absolute values, but AN showed higher bone resorption than CO when Pyd and Dpd excretion was adjusted by either creatinine (P<0.0000) or the SKM (P<0.05). Within the AN group, urinary excretion of both cross-links was significantly and consistently higher in ANp compared with ANr (P<0.05). However, these differences disappeared when crosslink output was adjusted either by urinary creatinine or SKM. RE subjects showed no differences in bone resorption with the AN group despite weight gain, being crosslink excretion consistently elevated compared to controls (Pyd: P<0.01 by creatinine and P<0.05 by SKM; Dpd: P<0.01 by creatinine and P<0.05 by SKM). CONCLUSION: Bone resorption is elevated in anorexia nervosa and different strategies for low-weight maintenance do not seem to have a differential impact. Increased bone resorption persists in subjects with past diagnosis of anorexia nervosa despite rehabilitation lasting more than 6 months. This finding indicates that bone mass and turnover should be monitored in anorexia nervosa patients and ex-patients well beyond recovery of normal body mass. Further investigation is warranted to examine the long-term effect of such prolonged increase in bone turnover at a young age.

Basal activity of the hypothalamic-pituitary-adrenal axis and cognitive function in anorexia nervosa.

Anorexia nervosa is associated with abnormalities in neuroendocrine function including sustained hypercortisolism, which has been shown elsewhere to be associated with impairment of function in learning, memory and attention. Cognitive impairment has also been observed in anorexia nervosa. These effects may be mediated in part through cortisol effects on the hippocampus, which is dense with glucocorticoid receptors. We investigated the association between cortisol levels and cognitive function in anorexia nervosa by measuring both 24-hour urinary cortisol counts and performance on tasks of learning, memory and attention in patients suffering from the disorder. Cortisol secretion was shown to be significantly higher in the patient group than in a matched control group and patients were also shown to be impaired in memory and attention. However, no correlations were found between the cognitive deficits and cortisol measures. It is suggested that more sensitive profiling of cortisol levels throughout the circadian cycle may be useful in future studies of cognitive function in anorexia nervosa.

Detection and importance of laxative use in adolescents with anorexia nervosa.

OBJECTIVE: The frequency of laxative use in adolescents with anorexia nervosa is poorly described. This study of adolescents with anorexia nervosa examined self-report and biochemical screening methods for the detection of laxative use, the pattern of laxative use in this population over time, and the associated medical complications and psychopathology. METHOD: Forty-three consecutive patients with anorexia nervosa were studied. Initial assessment encompassed psychiatric history, medical examination, and administration of the Eating Disorders Examination, Child Behavior Checklist, and Youth Self-Report. Biochemical investigations, including random urinary laxative screening, were performed at assessment and follow-up. RESULTS: The frequency of laxative use from self-report alone was 12%; combined with urine screening it was 19%. The frequency of laxative use increased to 32% with prospective follow-up. Medical complications were associated with laxative use at follow-up. Laxative use was associated with longer duration of disease and with higher scores on the Eating Disorders Examination subscale Eating Concern. CONCLUSIONS: Laxative use is common among adolescents with anorexia nervosa, and the risk of associated medical complications increases over time. Biochemical screening will improve detection of laxative use. Longer duration of illness and greater Eating Concern scores are associated with increased risk of laxative use, and monitoring patients at increased risk is important.

The dexamethasone-suppressed corticotrophin-releasing hormone stimulation test in anorexia nervosa.

OBJECTIVE: The dexamethasone-CRH test (combination of dexamethasone-induced suppression of HPA axis function and subsequent stimulation with oCRH) (Dex-CRH test) has been proposed to fully distinguish ACTH-dependent Cushing's disease (CD) from pseudo-Cushing's states (PCS), i.e. tumoural vs. functional hypercortisolism. A plasma cortisol concentration greater than 38 nmol/l 15 min after CRH injection has been demonstrated to identify all cases of CD and to exclude all cases of PCS. Although obviously not a PCS from a clinical point of view, anorexia nervosa (AN) is associated with CRH-driven hyperactivity of the HPA axis. This study reports the response of AN patients, a model of functional biological hypercortisolism, to the Dex-CRH test. PATIENTS AND METHODS: Nineteen women affected with anorexia nervosa and 6 healthy sex-matched controls were studied. RESULTS: Three of 19 AN patients had an abnormal 24-h urinary free cortisol excretion (UFC), whereas 1 of 19 AN had increased overnight UFC. AN subjects had inadequately suppressed plasma cortisol after low-dose dexamethasone suppression test (LDDST) (cortisol 192.8 +/- 63.4 vs. < 27 nmol/l, AN vs. controls, respectively). Seven of 19 AN patients had plasma cortisol levels above 50 nmol/l after LDDST. None of the AN patients had CRH-induced increases in plasma ACTH or cortisol (basal cortisol 192. 8 +/- 63.4 and peak cortisol 181.7 +/- 59.9 nmol/l). Despite unresponsivenessto CRH and because of the lack of suppression after dexamethasone, using the single plasma cortisol threshold value of 38 nmol/l obtained at 15 min during the Dex-CRH test would have been misclassified in half of our AN population (9 of 19). CONCLUSION: Since anorexia nervosa represents a model of functional hypercortisolism that shares similar pathophysiological mechanisms to the other causes of pseudo-Cushing's states, we suggest testing all causes of pseudo-Cushing's states using the dexamethasone-CRH approach to (i) describe the actual responses of clinically relevant pseudo-Cushing's states and (ii) to improve our knowledge of the pathophysiological discrepancies between the various causes of pseudo-Cushing's states. Lastly, the evaluation of dexamethasone metabolism (absorption, volume of distribution, clearance) may help to gain more insight into the diagnostic value of the dexamethasone-CRH test.

Urinary alpha and beta C-telopeptides of collagen I: clinical implications in bone remodeling in patients with anorexia nervosa.

Fragments derived from degradation of type I collagen C-telopeptide (CTX) can be nonisomerized (alpha) or beta-isomerized (beta) depending on the age of bone; i.e., mainly the alpha form is derived from new bone and the beta form from old bone. We have studied 41 female patients with anorexia nervosa (AN), aged 18.5 +/- 2.2 years (range 16-24 years), and with an evolution time between 1.5 and 11 years, and 31 healthy control females (C), with a mean age of 19 +/- 2.3 years (range 16-24 years). The AN patients showed a significant decrease in bone mass, with a mean Z-score of bone mineral density (BMD) of -3.2 +/- 0.8 (range -0.9 to -5.4). The aim of our study was to determine the levels of urinary alpha- and beta-CTX markers of bone resorption, the alpha/beta ratio (alpha/beta), and the level of bone alkaline phosphatase (bAP), a biochemical marker of bone formation, in order to relate them to the degree of osteopenia and the status of bone remodeling. Statistical analysis was by the Mann-Whitney test. The degree of osteopenia correlated with bAP levels (p = 0.0027) but not with the other parameters. Patients with AN were divided into three groups according to their levels of bAP: high (H), normal (N) or low (L). We found that BMD was significantly lower, and alpha- and beta-CTX were significantly higher, in groups H and N than in group L. Bone AP correlated significantly with alpha-CTX (p = 0.0042) and alpha/beta (0.0095) in the controls, but not with beta-CTX, while in AN patients bAP correlated with beta-CTX (p = 0.0000) and with alpha-CTX (p = 0.022) but not with the alpha/beta ratio. The ratio CTX/bAP (resorption/formation) was similar in AN patients and controls. It is concluded that: (1) patients with AN have a high degree of osteopenia which correlated with bAP levels; (2) urinary CTX fragments found in AN patients seem to come mainly from old bone (beta-CTX), while CTX found in healthy adolescent control females come from new bone (alpha-CTX). For this reason, alpha-CTX is more suitable than beta-CTX for measuring bone resorption in controls and beta-CTX is more suitable in patients with AN; (3) the resorption/formation ratio (CTX/bAP) was similar in AN patients and controls. From points (2) and (3) it is possible to suggest that, although bAP reflects bone formation in control females, this marker does not reflect effective bone mineralization in AN patients, a similar feature to that of patients with osteomalacia.

Leptin in relation to resumption of menses in women with anorexia nervosa.

Serum levels of leptin are decreased in underweight AN patients and increase with weight restoration. To assess the relationship of decreased leptin levels with other hormonal abnormalities in AN and to evaluate the possible role of increasing leptin levels, alone or in combination with other hormones, in the resumption of menses that accompanies weight gain, we studied cross-sectionally sixty-five consecutively enrolled AN patients. Subjects were divided in three groups: (I) underweight and amenorrheic; (II) weight-recovered but still amenorrheic; and (III) weight-recovered and eumenorrheic women. Patients in group I had decreased BMI, serum leptin, estradiol (E2), insulin-like growth factor 1 (IGF-1) and urinary growth hormone (GH) levels and increased sex hormone-binding globulin (SHBG) levels, compared to AN patients in groups II and III. Moreover, although no differences in leptin levels or BMI were observed between amenorrheic and eumenorrheic weight-recovered patients (groups II and III), free E2 and GH levels were higher (P<0.02) in weight-recovered, eumenorrheic women. Thus, it appears that leptin is a necessary, but not a sufficient, factor for the resumption of menses in AN patients.

Dissociation of bone turnover in anorexia nervosa.

Biochemical markers were measured to assess bone turnover in a cross-sectional study of 43 patients with anorexia nervosa; 28 were at their first assessment (untreated) with a body mass index (BMI) (median interquartile range) of 13.3 (2) kg/m2. A second group of 15 patients undergoing treatment (treated) had a median BMI of 17.6 (2.8) kg/m2. The median, interquartile range of urinary deoxypyridinoline (DPyd), a bone resorption marker, was raised in both groups compared with an age-matched control population [DPyd = 17.8 (15.2), 17.5 (16.4) and 9.2 (4.0) nmol/mmol creatinine, respectively]. Serum type 1 collagen carboxyterminal propeptide (P1CP), a marker of bone formation, was similar to controls in the untreated patients [112 (29) and 112 (78.5) ng/ml, respectively], but was significantly raised in the treated patients [163 (219) ng/ml, P < 0.05]. A second group of 21 patients was followed prospectively, on admission and during 8 weeks of intensive inpatient care (BMI on admission and after 8 weeks was 13.0 (2) and 16.7 (3) kg/m2, respectively). The resorption marker, serum type 1 collagen carboxyterminal telopeptide (1CTP) was raised on admission and remained high during treatment. P1CP and osteocalcin levels were similar to control levels on admission but increased with treatment, and after 8 weeks were 40% and 63% higher respectively than on admission. These findings suggest that in untreated anorexia nervosa there was uncoupling of bone turnover as bone resorption markers were raised without a concomitant increase in bone formation markers. As the condition was treated and patients gained weight, the formation markers also increased, leading to a more balanced, although higher, bone turnover.

The acute effects of starvation on 6-sulphatoxy-melatonin output in subgroups of patients with anorexia nervosa.

Sequential measures of daytime and nighttime sulphatoxy-melatonin (aMT6s) in 10 female patients with anorexia nervosa (AN) and 12 female patients with concurrent AN with bulimic symptoms (AN + BN) were compared with 13 female control subjects. The AN + BN group displayed a significant increase in aMT6s output in the acutely symptomatic state compared with both AN patients and controls. However, there were no subsequent differences after 7 or 14 days between the two patient groups. The AN + BN group also initially demonstrated a significant increase in daytime output of aMT6s compared to nighttime with a trend toward reversing this pattern after 7 and 14 days. Altered melatonin output may influence the course of illness or reflect greater disruption of circadian rhythm in those anorexic patients who also binge and purge compared to restricting anorexics.

Zinc status before and after zinc supplementation of eating disorder patients.

Reduced food consumption is a major manifestation of zinc (Zn) deficiency. Many manifestations of Zn deficiency are complications of anorexia nervosa and bulimia nervosa. We evaluated serum and 24-hour urinary Zn values in 12 healthy volunteers and 33 eating disorder patients before and after hospitalization which included either Zn supplementation (75 mg Zn/day) or placebo. Bulimics had depressed serum Zn concentrations (p < 0.025). Admission urinary Zn was lower in bulimics (258 +/- 44 micrograms/day), and significantly depressed in anorexics (196 +/- 36 micrograms/day, p < 0.005) vs controls (376 +/- 45 micrograms/day). During hospitalization, serum Zn concentrations increased in all supplemented patients vs no change with placebo. Urinary Zn excretion increased in supplemented bulimics (p < 0.001) and placebo (p < 0.05). Urinary Zn excretion markedly increased in supplemented anorexics (179 +/- 65 to 1052 +/- 242 micrograms/day); however, placebo values fell or remained unacceptably low (admission 208 +/- 48 micrograms/day; discharge 160 +/- 17 micrograms/day). By dietary history, controls consumed the Recommended Dietary Allowance (RDA) for Zn (11.95 +/- 1.25 mg/day); anorexics 6.46 +/- 1.14 mg/day; and bulimics 8.93 +/- 1.29 mg/day. We suggest that Zn deficiency may act as a "sustaining" factor for abnormal eating behavior in certain eating disorder patients.

Glucocorticoid receptors in lymphocytes in anorexia nervosa.

OBJECTIVE: The aim was to explore the down-regulation of the glucocorticoid receptors during hypercortisolaemia in anorexia nervosa. DESIGN: Urine and plasma samples were obtained for cortisol determination and blood lymphocytes were isolated for receptor binding studies. PATIENTS: Sixteen anorexic patients, aged 16-27 years, with a mean +/- SEM body mass index of 14.2 +/- 2.0 (ranging from 11.1 to 17.4), and 15 normal women were studied. Six patients were reinvestigated after a significant weight gain. MEASUREMENTS: The binding capacity and affinity of the glucocorticoid receptors were measured with dexamethasone as ligand on lymphocytes. RESULTS: In patients, both total and free plasma cortisol concentrations were higher than in the normal women, as was their urinary free cortisol; the number of glucocorticoid receptors per cell (Ro) and the binding affinity (Kd) for dexamethasone were, however, not significantly different (Ro: 7687 +/- 1750 vs 7347 +/- 1285 sites/cell; Kd: 7.7 +/- 2.4 vs 7.4 +/- 1.7 nM at 24 degrees C). After weight gain (14 +/- 2 to 16 +/- 2 kg/m2), receptor numbers were 8421 +/- 2126 (pre) and 9011 +/- 500 (post) sites/cell, which are not significantly different (P greater than 0.2); the Kd was unchanged (9.3 +/- 2.6 vs 9.2 +/- 2.4 nM). CONCLUSIONS Hypercortisolaemia does not down-regulate the lymphocyte glucocorticoid receptors in anorexia nervosa and a post-receptor defect might be involved in peripheral tissue resistance to the effects of glucocorticoid hormones in undernutrition.

Pellagra in a patient with an eating disorder.

A case of pellagra is described that occurred in a patient with an eating disorder and who presented with marked photosensitivity and diarrhoea. We found urinary 5-hydroxy-indole-acetic acid to be low and suggest that this may be a useful screening test. To our knowledge this is only the second reported case of pellagra associated with an eating disorder.

Urinary C-peptide excretion in obese and anorectic children.

To assess the total insulin secretion in children in different nutritional states we have analysed the 24 h urinary C-peptide excretion in 32 obese children (16 boys and 16 girls) 8-15 years of age as well as in 7 girls with anorexia nervosa 11-16 years of age. Obese children had a median urinary C-peptide excretion rate of 0.27 nmol/kg/24 h, which was not different from that of a group of normal-weight children. In the group of anorectic girls, on the other hand, the median value 0.47 nmol/kg/24 h was significantly (p less than 0.05) higher than for normal-weight girls of the same age (median = 0.26 nmol/kg/24 h). These results indicate that in obese children insulin secretion, measured as the 24 h urinary C-peptide excretion per kg body weight, is the same as in normal-weight children. Total insulin secretion is consequently increased. In anorexia nervosa, on the other hand, the higher C-peptide excretion per kg body weight compared with normal-weight children, indicates that insulin secretion is increased in relation to body weight.

Sulphatoxy melatonin: an index of depression in anorexia nervosa and bulimia nervosa.

Urinary excretion of the principal melatonin metabolite, sulphatoxy melatonin (aMT6s), was assessed both during the day and during the night in 38 female eating disorder patients (anorexia nervosa, n = 17; bulimia nervosa, n = 12; anorexia nervosa + bulimia nervosa, n = 9) and 14 female control subjects. Correlations between nocturnal serum melatonin and urinary aMT6s were also obtained. All patient groups and the controls showed a preservation of diurnal rhythm with elevated nocturnal urinary aMT6s values and no significant difference in amplitude between groups. However, patients with concurrent major depression had significantly lower levels of daytime and nighttime urinary aMT6s than the nondepressed group. Weight did not influence these findings. Correlations between nocturnal serum melatonin levels and urinary aMT6s were high for control subjects (r = 0.77) and moderate for the patient groups (r = 0.31). This may reflect differences in the rate of excretion of melatonin between patients and controls.