I. Ronald Shenker

The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa.

INTRODUCTION Osteopenia is a serious complication of anorexia nervosa (AN). Although in other states of estrogen deficiency, estrogen replacement therapy increases bone mass, its role in AN remains unresolved. STUDY OBJECTIVE To study the effect of estrogen-progestin administration on bone mass in AN. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study of 50 adolescents with AN (mean age 16.8 +/- 2.3 yrs) was conducted in a tertiary referral center. MAIN OUTCOME MEASURES Bone mineral density (BMD) of the lumbar spine and left hip were prospectively measured using dual-energy x-ray absorptiometry at baseline and annually. INTERVENTIONS Twenty-two subjects received estrogen-progestin and 28 standard treatment (Rx) alone. Estrogen-progestin was administered daily as an oral contraceptive containing 20-35 mcg ethinyl estradiol. All subjects received calcium supplementation and the same medical, psychological, and nutritional intervention (standard Rx). Mean length of follow-up was 23.1 +/- 11.4 months. RESULTS At presentation, patients were malnourished (79.5% +/- 7.6% IBW), hypoestrogenemic (estradiol 24.7 +/- 10.7 pg/mL), and had reduced bone mass (lumbar spine BMD -2.01 +/- 0.69 SD below the young adult reference mean). Ninety-two percent of subjects were osteopenic and 26% met WHO criteria for osteoporosis. Body weight, and no treatment group, was the major determinant of BMD. At one-year follow-up, there were no significant differences in absolute values or in net change of lumbar spine or femoral neck BMD between those who received estrogen-progestin and those who received standard Rx (80% power of finding a 3% difference in BMD at 1 yr). In those followed for 2-3 yrs, osteopenia was persistent and in some cases progressive. CONCLUSION In our study population, estrogen-progestin did not significantly increase BMD compared with standard Rx. These results question the common practice of prescribing hormone replacement therapy to increase bone mass in AN.

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.

Subclinical versus formal eating disorders: Differentiating psychological features

Sixty referrals to a Pediatric Eating Disorder clinic were compared on a number of demographic, clinical, and psychological variables. Twelve patients met definite diagnostic criteria for anorexia nervosa and 14 met criteria for a diagnosis of bulimia nervosa. Twenty-one patients had a subclinical form of anorexia nervosa and eight had subclinical bulimia nervosa. Five patients could not be classified. The subclinical and definite diagnostic groups were compared across a number of demographic, eating pathology, and general psychological variables. The results revealed a clear pattern of difference between the two bulimia nervosa groups on variables related to the regulation of affects and impulses. There was no clear pattern of difference between the definite and subclinical anorexia nervosa groups. The results suggest that the DSM-III-R criteria for anorexia nervosa may substantially underestimate the number of individuals with a psychologically distressing eating disorder, but provide tentative support for the maintenance of strict diagnostic criteria for bulimia nervosa.

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.

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.

Hypophosphatemia during nutritional rehabilitation in anorexia nervosa: implications for refeeding and monitoring

PURPOSE To determine the incidence of hypophosphatemia in adolescents with anorexia nervosa (AN) hospitalized for nutritional rehabilitation and to examine factors predisposing to its development. METHODS A retrospective chart review of 69 patients (66 female, 3 male) with AN consecutively admitted to an inpatient adolescent medical unit between July 1, 1998 and June 30, 2000. Mean age was 15.5 +/- 2.4 (range 8 to 22) years and mean % ideal body weight (IBW) was 72.7 +/- 7%. Serum phosphorus was measured daily for 1 week and then biweekly to weekly. Patients were started on 1200-1400 kcal/day and calories were increased by 200 kcal every 24-48 hours. RESULTS Four (5.8%) patients developed moderate hypophosphatemia (<2.5 and > or = 1.0 mg/dl) and 15 (21.7%) had mild hypophosphatemia (<3.0 and > or = 2.5 mg/dl). Patients who developed moderate hypophosphatemia were significantly more malnourished than those who did not (p = 0.02). Phosphorus nadirs were directly proportional to % IBW (r = 0.3, p = 0.01). Over three-quarters of the patients (81%) reached their phosphorus nadir within the first week of hospitalization. The patient with the lowest phosphorus level experienced short runs of ventricular tachycardia. No other severe complications were seen. Overall, 19 (27.5%) patients required phosphorus supplementation. CONCLUSIONS Phosphorus drops to its nadir during the first week of refeeding. We recommend daily monitoring of serum phosphorus with supplementation as needed during the first week of hospitalization, especially in those who are severely malnourished.

Body shape concerns among adolescents

The Body Shape Questionnaire (BSQ) is a 34-item self-report questionnaire that measures the degree of body shape dissatisfaction. To date, the BSQ has not been used with adolescents. The present study compared the BSQ scores of five adolescent subject samples: Anorexia Nervosa (AN), Bulimia Nervosa (BN), Subclinical Bulimia Nervosa (SB), Subdinical Anorexia Nervosa (SA), and non-eating-disordered adolescent females (Q. Results show that patients with BN have the highest levels of body dissatisfaction. All clinical groups had higher BSQ scores than subjects in the comparison sample but only the BN patients had significantly higher scores. The mean BSQ score for the Comparison group was higher than published means for non-eating-disordered adult samples. The two major findings of the study are that significant body shape concerns are particular features of patients with bulimia nervosa but that some body shape concerns are common among non-eating-disordered adolescent females.

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.

Resolution of vital sign instability: an objective measure of medical stability in anorexia nervosa

PURPOSE To determine the amount of time necessary for stabilization of blood pressure and heart rate in patients with anorexia nervosa (AN) and the percentage of ideal body weight (IBW) at which this occurs. METHODS A retrospective study was conducted on 36 adolescent patients (33 F, 3 M) with AN, restricting type (Diagnostic and Statistical Manual of Mental Disorders, Fourth edition [DSM-IV] criteria), admitted to a specialized eating disorders unit for nutritional rehabilitation between October 1996 and August 1998. Mean age was 16.5 +/- 2.5 years, range 12-23 years. Each morning, pulse and blood pressure were measured supine and after standing for 2 minutes using an automated blood pressure/pulse measuring device (Dynamap). Orthostasis was defined as a drop in systolic blood pressure > 20 mm Hg with or without a drop in diastolic blood pressure > 10 mm Hg or an increase in heart rate >20 bpm on standing. Time of resolution of orthostasis was defined as the day after which the patient was no longer orthostatic for 48 hours. RESULTS On admission mean pulse rate was 54.4 +/- 14.8 bpm (range 38-78) and mean pulse rate slowly increased to 70 bpm by Day 12 of hospitalization. On admission, 60% of patients had orthostatic pulse changes and with refeeding, this number increased to 85% by Day 4 of admission. The mean number of days until patients were no longer orthostatic was 21.6 +/- 11.1 days and resolution of orthostasis occurred when subjects reached 80.1 +/- 5.7% of IBW. Orthostatic pulse changes were more sensitive indicators of hemodynamic instability than orthostatic blood pressure changes and took longer to resolve. CONCLUSION This study demonstrates that of patients with AN, the majority have orthostatic pulse changes on admission. Normalization of orthostatic pulse changes was achieved after approximately 3 weeks of nutritional rehabilitation when subjects reached 80% of their IBW. Resolution of orthostasis can be used as one of the objective measures to determine medical stability and readiness for discharge to an alternate level of care.

Adverse Health Behaviors and Depressive Symptomatology in Adolescents

The Beck Depression Inventory (BDI) and a Health Behavior Questionnaire (HBQ) were administered to 398 junior and senior high school students to assess the relationship between health behaviors and depressive symptomatology. Adverse health behaviors which included cigarette smoking, alcohol use, marijuana use, and the use of drugs other than marijuana were highly intercorrelated. Age of the subjects and BDI items explained up to 31% of the variance of the adverse health behaviors. The suicidal ideation and hopelessness items of the BDI and age of the subjects accounted for most of the explained variance (28%) in adverse health behaviors.