Cardiac arrest and delirium: presentations of the refeeding syndrome in severely malnourished adolescents with anorexia nervosa.

AIM: To describe the clinical presentation of the refeeding syndrome and highlight the dangers of performing nutritional rehabilitation too rapidly in a severely malnourished patient. DESIGN: Retrospective case review of adolescents admitted with anorexia nervosa who developed the refeeding syndrome. RESULTS: Between July 1993 and July 1994, 3 of 48 adolescent females developed the refeeding syndrome. While the cardiac complications occurred in the first week of refeeding, the delirium characteristic of this syndrome occurred later and was more variably related to hypophosphatemia. OBSERVATIONS: Refeeding malnourished patients with anorexia nervosa can be associated with hypophosphatemia, cardiac arrhythmia and delirium. Refeeding patients with anorexia nervosa who are < 70% of ideal body weight should proceed with caution, and the caloric prescription should be increased gradually. Supplemental phosphorus should be commenced early and serum levels maintained above 3.0 mg/dL. Cardiac and neurologic events associated with refeeding are most likely to occur within the first weeks, justifying close monitoring of electrolyte and cardiac status.

The metabolic responses to starvation and refeeding in adolescents with anorexia nervosa.

Adaptive changes in metabolism result in decreased energy requirements in AN. A retrospective study of 21 hospitalized female AN patients demonstrated that indirect calorimetry (IC) measurement of resting energy expenditure (REE) was significantly lower than REE calculated by the Harris-Benedict equation (HBE). The HBE was adjusted by multiple-regression analysis to reflect the hypometabolic state of AN, and the adjusted equation was prospectively validated in 37 hospitalized female AN patients. Refeeding requires an understanding of both baseline requirements and metabolic changes that occur during nutritional rehabilitation. In our present study, we prospectively evaluated changes in fasting and postprandial REE in 50 hospitalized female patients meeting DSM-IV criteria for AN. Baseline IC measurements of fasting and postprandial REE were obtained within three days of admission, and every two weeks thereafter. Mean fasting REE increased significantly from 72 (+/-11.7) to 83.2 (+/-12.6) percent of predicted (p < 0.001) during the first two weeks of hospitalization. Likewise, postprandial REE also increased significantly from 17.5 (+/-18.2) to 27.9 (+/-15.9) percent above fasting REE during the same time period (p < 0.01). Significant increases in both REE and postprandial REE persisted in patients requiring longer hospitalizations. Despite the fact that prescribed energy intake and triiodothyronine (T3-RIA) levels increased during refeeding, there was no significant relationship between postprandial REE and energy intake or T3 levels after baseline. We conclude that energy metabolism in AN adapts to semistarvation by a reduction in fasting REE. With refeeding there is a reversal of this adaptive function, demonstrated by an increase in both fasting and postprandial energy expenditure. The increase in postprandial REE is not related to energy intake or thyroid function.

Resumption of menses in anorexia nervosa.

OBJECTIVE: To determine factors associated with resumption of menses (ROM) in adolescents with anorexia nervosa. DESIGN: Cohort study with 2-year follow-up. SETTING: Tertiary care referral center. PATIENTS: Consecutive sample of 100 adolescent girls with anorexia nervosa. INTERVENTIONS: Body weight, percent body fat, and luteinizing hormone, follicle-stimulating hormone, and estradiol levels were measured at baseline and every 3 months until ROM (defined as 2 or more consecutive spontaneous menstrual cycles). Treatment consisted of a combination of medical, nutritional, and psychiatric intervention aimed at weight gain and resolution of psychological conflicts. MAIN OUTCOME MEASURES: Body weight, body composition, and hormonal status at ROM. RESULTS: Menses resumed at a mean (+/-SD) of 9.4 +/- 8.2 months after patients were initially seen and required a weight of 2.05 kg more than the weight at which menses were lost. Mean (+/-SD) percent of standard body weight at ROM was 91.6% +/- 9.1%, and 86% of patients resumed menses within 6 months of achieving this weight. At 1-year follow-up, 47 (68%) of 69 patients had resumed menses and 22 (32%) remained amenorrheic. No significant differences were seen in body weight, body mass index, or percent body fat at follow-up in those who resumed menses by 1 year compared with those who had not. Subjects who remained amenorrheic at 1 year had lower levels of luteinizing hormone (P < .001) and follicle-stimulating hormone (P < .05) at baseline and lower levels of luteinizing hormone (P < .01) and estradiol (P < .001) at follow-up. At follow-up, a serum estradiol level of more than 110 pmol/L (30 pg/mL) was associated with ROM (relative risk, 4.6; 95% confidence interval, 1.9-11.2). CONCLUSIONS: A weight approximately 90% of standard body weight was the average weight at which ROM occurred and is a reasonable treatment goal weight, because 86% of patients who achieved this goal resumed menses within 6 months. Resumption of menses required restoration of hypothalamic-pituitary-ovarian function, which did not depend on the amount of body fat. Serum estradiol levels at follow-up best assess ROM.

Directly observed preventive therapy. Turning the tide against tuberculosis.

OBJECTIVE: To compare compliance between directly observed preventive therapy and daily treatment for students with inactive (class II) tuberculosis. DESIGN: Cohort analytic study and cost-effectiveness analysis. Students found to be positive for purified protein derivative and having no abnormal chest x-ray films on mandated screening were advised to have prophylactic treatment with isoniazid. Treatment was either directly observed in the school health clinic or provided as daily therapy by the Department of Health. Treatment completion, age, sex, ethnicity, and recent immigration were compared between the 2 treatment groups. SETTING: A school-based clinic at an inner-city New York, NY, high school. RESULTS: In 1993, 864 students were screened. The positive purified protein derivative rate was 19.3%. All 161 students had negative findings on chest x-ray films. Of the students, 105 (65.2%) were enrolled in the school-based clinic directly observed preventive therapy program, 22 were referred to the Department of Health for daily therapy, and 34 excluded from the study before treatment. The 2 treatment groups did not differ in composition. Completion of therapy in the directly observed preventive therapy group (87.6%) was significantly greater than that in the daily therapy group (50%) (P = 0.001, X2 = 11.8) and that reported in the literature for programs other than directly observed preventive therapy (30%-70%). Directly observed preventive therapy was administered by existing personnel without additional expenditure. CONCLUSION: Directly observed preventive therapy is an effective strategy that should be used in the school clinic setting to increase compliance with prophylactic treatment for tuberculosis.

Reversibility of cerebral ventricular enlargement in anorexia nervosa, demonstrated by quantitative magnetic resonance imaging.

OBJECTIVE: To determine the reversibility of the loss of brain parenchyma and ventricular enlargement in patients with anorexia nervosa after refeeding. STUDY DESIGN: Quantitative magnetic resonance imaging was performed on three groups of subjects: (1) 12 female adolescents hospitalized with anorexia nervosa, (2) the same 12 patients after nutritional rehabilitation, a mean of 11.1 months later, and (3) 12 healthy age-matched control subjects. Sixty-four contiguous coronal magnetic resonance images, 3.1 mm thick, were obtained. With a computerized morphometry system, lateral and third ventricular volumes were measured by a single observer unaware of the status of the patient. RESULTS: On admission, patients were malnourished and had lost an average of 11.7 kg (body mass index, 14.3 +/- 2.0 kg/m2). After refeeding, they gained an average of 9.7 kg (body mass index, 17.9 +/- 1.5 kg/m2). Total ventricular volume decreased from 17.1 +/- 5.5 cm3 on admission to 12.4 +/- 3.0 cm3 after refeeding (p < 0.01) and returned to the normal range. The degree of enlargement of the third ventricle was greater than that of the lateral ventricles. There was a significant inverse relationship between body mass index and total ventricular volume (r = -0.63; p < 0.05). CONCLUSION: In patients with anorexia nervosa, cerebral ventricular enlargement correlates with the degree of malnutrition and is reversible with weight gain during long-term follow-up.

Medical complications in male adolescents with anorexia nervosa.

PURPOSE: Medical information on male anorectics is scant. We present data on 10 males with anorexia nervosa, who were treated at our Eating Disorders Center during a twelve-year period. METHODS: Retrospective chart review. RESULTS: All patients were malnourished weighing 80% or less of their ideal body weight with a mean B.M.I. of 13.5 +/- 2.0. Height below the 50th percentile was evident in 80% of the patients, and was below the 10th percentile in 30% of the patients. Structural brain changes on brain computerized tomography scans were noted in seven out of nine patients and more than 50% had mild anemia relative to the Tanner stage. Other findings included a mean presenting heart rate of 68.3 +/- 17: four out of ten patients had presenting heart rates of 80 or greater and of these, three had serious medical problems and were severely malnourished. Two patients had cardiac complications and one had a life-threatening electrolyte disturbance. CONCLUSION: Despite the small number of patients, the proportion of male adolescent anorectics with medical abnormalities seems high, and may be due to difficulties in establishing the diagnosis and delay in seeking medical attention. Patients who had heart rates of 80 or greater were perhaps sicker and further along in their development of congestive heart failure, thus explaining their initial relative tachycardia. We suggest a higher index of suspicion for congestive heart failure and closer medical monitoring when a malnourished adolescent with anorexia nervosa presents with relatively elevated heart rates.

Disturbances in growth hormone secretion and action in adolescents with anorexia nervosa.

Women in whom anorexia nervosa develops during adolescence have failure of linear growth associated with low levels of insulin-like growth factor I (IGF-1). To investigate the pathophysiology of growth retardation in adolescents with anorexia nervosa, we measured basal growth hormone (GH), growth hormone-binding protein (GHBP), IGF-1, and insulin-like growth factor binding protein-3 (IGFBP-3) in three groups of patients: (1) 28 recently hospitalized female adolescents with anorexia nervosa, (2) 23 of the same patients after partial weight restoration, and (3) 28 healthy control subjects matched for age, sex, and pubertal stage. Fasting GH levels in group 1 did not differ significantly from those in group 3. In contrast, serum GHBP (p < 0.001), IGF-1 (p < 0.001), and IGFBP-3 (p < 0.01) were significantly lower in group 1 than in group 3. Serum GHBP and IGFBP-3 levels were positively correlated with body mass index. Serum GHBP levels were low in patients in all five pubertal stages and even in those shown to have adequate GH secretion. In group 2 (after refeeding) the serum IGF-1 concentration increased significantly and GHBP and IGFBP-3 returned to normal. We conclude that patients with anorexia nervosa have diminished GH action resulting in decreased secretion of IGF-1. The positive correlation with body mass index and the reversibility with refeeding suggest that these changes are secondary to malnutrition. Altered GH function that occurs during the years of active growth can explain the growth retardation seen in anorexia nervosa.

Amenorrhea in anorexia nervosa. Neuroendocrine control of hypothalamic dysfunction.

Amenorrhea is one of the cardinal features of anorexia nervosa and is associated with hypothalamic dysfunction. Earlier theories of weight loss, decreased body fat, or exercise do not fully explain the etiology of amenorrhea in anorexia nervosa. Disturbances in central dopaminergic and opioid activity have been described in anorexia nervosa and both these substances are known to modulate gonadotropin-releasing hormone (GnRH)-mediated luteinizing hormone (LH) release. Serum LH, follicle-stimulating hormone (FSH), estradiol, and prolactin levels were measured at baseline and after administration of metoclopramide (a central D-2 dopamine receptor blocker) in 10 newly diagnosed women with anorexia nervosa and in 10 healthy age-matched controls. Basal prolactin levels and the prolactin response to metoclopramide were significantly impaired in the group with anorexia nervosa. Metoclopramide did not induce a significant rise in LH levels in either the anorexic or the control groups. Neurotransmitter abnormalities may influence hypothalamic dysfunction in anorexia nervosa but the exact mechanism remains to be determined.

Adolescent obesity and cardiovascular risk: a rational approach to management.

Ten obese adolescents, referred because of elevated cardiovascular disease risk, were treated in a pediatric atherosclerosis prevention center. The focus of treatment was an increase in exercise tolerance and aerobic capacity and a decrease in the percentage of fat in the diet. Weight loss was not a goal of treatment, but continued growth with a slowing of the rate of weight gain was emphasized. All patients were at elevated cardiovascular risk at the entry to the study, and nine of the ten had significant improvements in one or more of their cardiovascular risk parameters. Furthermore, with regard to body composition, eight of the ten patients were able to improve their body mass index. On average, triceps skinfold thicknesses declined 25 percent. Total cholesterol declined 14%, triglycerides declined 33%, LDL cholesterol declined 13%, and HDL cholesterol did not change with this form of treatment. As for systolic and diastolic blood pressure, four of the ten patients who had elevated blood pressures at the initiation of treatment were able to decrease their blood pressure, in absolute terms and on the basis of their percentiles for age and sex. We conclude that, in obese adolescents, improved diet and body composition, a slowed rate of weight gain, and a reduction of cardiovascular risk shown through lipid profiles and blood pressures can be achieved from a multidisciplinary treatment program focused on achievable goals. These goals include (1) increased habitual exercise and increased aerobic exercise and (2) a decrease in the percentage of energy intake from fat and saturated fat, with a concomitant decrease in the balance of energy intake to energy output. It is important to remember that we did not focus on weight loss per se and that the treatment was individualized to the developmental stage of the adolescent.

Passive smoking alters lipid profiles in adolescents.

Although cigarette smoking is associated with elevation of plasma lipid levels and changes in lipoprotein distribution, it is not known whether passive smoking is associated with an alteration in lipid profiles. The relation between plasma cotinine, a marker of exposure to tobacco smoke, and lipid profiles was studied in healthy adolescents from a suburban New York high school district who were undergoing preparticipation sports physicals. Forty-four percent of the adolescents reported that one or both parents currently smoked. Eleven percent of the adolescents had plasma cotinine concentrations greater than or equal to 2.5 ng/mL, the level considered indicative of exposure. Adolescents with two smoking parents had significantly higher plasma cotinine concentrations after adjustment for other factors than adolescents whose parents did not smoke. Plasma cotinine concentration greater than or equal to 2.5 ng/mL was associated with an 8.9% greater ratio of total cholesterol to high-density lipoprotein cholesterol (P less than .003) and a 6.8% lower high-density lipoprotein cholesterol (P less than .03). These results suggest that passive smoking, like active smoking, leads to alterations in lipid profiles predictive of an increased risk of atherosclerosis.

Chest pain in adolescents.

Adolescents with chest pain were compared with healthy adolescents to determine if they were more likely to believe they had cardiac disease and were less healthy than their peers. Perceptions were examined with a questionnaire and results analyzed by chi 2 analysis. Twenty-two percent of adolescents with chest pain were diagnosed with cardiac problems, a prevalence rate higher than previous reports. While knowledge of possible etiologies of chest pain was similar for both patient and control groups, 68% of those with the symptom associated their own pain with heart disease and 44% altered their behavior because of it. Health professionals should avoid inadvertent reinforcement of the patient's fear of heart disease, particularly because subsequent unnecessary self-restrictions can result in an age group in which the symptom most often represents a noncardiac etiology.

Effect of weight restoration on the dyslipoproteinemia of anorexia nervosa.

Dyslipoproteinemia, a risk factor for atherosclerosis, has been described in anorexia nervosa (AN). To assess whether dyslipoproteinemia is present in our AN population, and to investigate the effect of controlled refeeding, we prospectively examined lipid profiles in 16 hospitalized adolescents with anorexia nervosa on admission and at discharge with a body weight of 90% of ideal. Healthy high school females served as controls. Total cholesterol concentration was not different from controls at either time, and there was no change with weight restoration. Triglyceride levels decreased significantly with treatment, and at discharge, levels were significantly lower than controls. High-density lipoprotein-cholesterol (HDL-C) levels increased significantly with weight gain, and were significantly higher than controls at discharge. Apoprotein A1, the major structural protein of high-density lipoprotein, was also significantly higher among the AN patients after weight gain. Low-density lipoprotein-cholesterol (LDL-C) values did not change, but apoprotein B was significantly higher than controls at discharge. The dyslipoproteinemia demonstrated in our patients was characterized by elevated HDL-C and apoprotein A levels with normal LDL-C and low triglyceride concentrations. These changes were accentuated by restoring body weight.

Blunted growth hormone responses to clonidine in adolescent girls with early anorexia nervosa. Evidence for an early hypothalamic defect.

We studied growth hormone (GH) levels in 14 adolescents with anorexia nervosa (AN), 12-20 years of age. All had amenorrhea and the duration of symptoms ranged from 2-24 months. There was no difference in unstimulated GH between the girls with AN and endocrinologically normal girls. However, the GH response to the alpha-adrenergic agent clonidine was blunted (less than 10 ng/ml) in 11 of 14 girls with AN. Our results of a normal basal GH level and blunted response to stimulation is in contrast to some reports of high basal GH levels and an exaggerated response to pituitary stimulation although it agrees with other studies. Our patient population was younger and at an earlier stage of the disease (12 with symptoms for less than 1 year) than the AN patients previously reported to have elevated GH secretion. In view of studies that report an elevated GH response to growth hormone releasing factor, our results suggest that the AN patient's abnormalities in GH secretion may result from an abnormal hypothalamic response to adrenergic stimuli. This hypothalamic abnormality might also contribute to the growth failure seen in adolescent girls with AN.

Attitudes versus performance in providing gynecologic care to adolescents by pediatricians.

This study ascertained current pediatric attitudes verses performance in caring for adolescent females in private practices in a suburban area. Sixty-seven randomly selected pediatricians were given a confidential questionnaire; 90% responded. Areas assessed were attitudes and practice about sexual history, breast examination, teaching self-breast examination, and vaginal examination. Comparisons were made between the different age groups and between male and female pediatricians. Ninety-two percent of pediatricians felt it was important to take a sexual history by age 16 years, while only 73% actually did. More female than male pediatricians thought it was important to take a sexual history and actually did so. Seventy-five percent stated that a breast examination should be routine, and most performed the examination. However only 60% taught self-breast examination despite the fact that 93% believed it was important. An internal vaginal examination as part of a routine physical was performed by only 7%. For specific gynecologic problems most asked to see the patient but most did not do an internal examination. The most likely indication for a pelvic examination was a vaginal discharge, but only 28% of the pediatricians would examine their patient for this complaint. Of the pediatricians who do the examination, 41% were not sure they had received the proper training. These data suggest that despite the American Academy of Pediatrics' recommendations that pediatricians continue the care of patients until age 21 years, there does not appear to be optimal care provided to female adolescent patients.

Reduction in pulmonary function and increased frequency of cough associated with passive smoking in teenage athletes.

Previous studies have suggested that passive smoking (involuntary inhalation of tobacco smoke by nonsmokers) reduces small airways function. We evaluated the exposure to passive smoking and its effects on pulmonary function and symptoms in a group of 12- to 17-year-old high school athletes (N = 209; 119 boys and 90 girls) at their annual presport participation physical examinations. A structured interview was used to assess pulmonary symptoms, personal smoking habits, and passive cigarette smoke exposure. All athletes performed forced expiratory maneuvers on a portable spirometer. We measured forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow 25% to 75% (FEF25-75). The best of three FEF25-75 measured was used. Less than 70% of predicted FEF25-75 was considered abnormal. Of the 209 athletes, 7.7% were active smokers and were excluded. Of the remaining 193 athletes, 68.4% were currently exposed to passive smoking. We found a fourfold increase in incidence of low FEF25-75 and/or cough in athletes exposed to passive smoking compared with athletes not exposed: 18 of 132 exposed athletes (13.6%) had low FEF25-75 and/or cough compared with two of 61 unexposed athletes (3.3%) who had low FEF25-75 and cough (P = .02). Boys were more frequently exposed to passive smoking than girls (74% of boys [80/108] v 61% of girls [52/85] ), but the effects were more pronounced in girls. These data show a relationship between exposure to passive smoking and early pulmonary dysfunction in young athletes. The frequent exposure to passive smoke and the high prevalence of dysfunction in this population, generally considered to be healthy, is of particular concern.