Neville H. Golden

Eating disorders in adolescents: A background paper

Although eating disorders primarily affect adolescents and young adults, much of the recent medical and psychiatric literature fails to consider the unique physiologic, psychologic, and developmental issues relevant to younger patients, more often describing older patients with more chronic and intractable disease. Pediatricians and adolescent medicine specialists see younger patients who have a shorter duration of illness and a different set of physiologic and psychologic responses to weight control. The Practice Guidelines for Eating Disorders, published in 1993 by the American Psychiatric Association (1), provide an excellent overview of the

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.

Optimizing Bone Health in Children and Adolescents

The pediatrician plays a major role in helping optimize bone health in children and adolescents. This clinical report reviews normal bone acquisition in infants, children, and adolescents and discusses factors affecting bone health in this age group. Previous recommended daily allowances for calcium and vitamin D are updated, and clinical guidance is provided regarding weight-bearing activities and recommendations for calcium and vitamin D intake and supplementation. Routine calcium supplementation is not recommended for healthy children and adolescents, but increased dietary intake to meet daily requirements is encouraged. The American Academy of Pediatrics endorses the higher recommended dietary allowances for vitamin D advised by the Institute of Medicine and supports testing for vitamin D deficiency in children and adolescents with conditions associated with increased bone fragility. Universal screening for vitamin D deficiency is not routinely recommended in healthy children or in children with dark skin or obesity because there is insufficient evidence of the cost–benefit of such a practice in reducing fracture risk. The preferred test to assess bone health is dual-energy x-ray absorptiometry, but caution is advised when interpreting results in children and adolescents who may not yet have achieved peak bone mass. For analyses, z scores should be used instead of T scores, and corrections should be made for size. Office-based strategies for the pediatrician to optimize bone health are provided. This clinical report has been endorsed by American Bone Health.

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.

Depression, self-esteem, and life events in adolescents with chronic diseases

This study assesses whether nonhospitalized adolescents with chronic diseases differ from their healthy peers on standardized measurements of depression, self-esteem, and life events. The study group consisted of 80 patients (20 with sickle cell disease, 40 with asthma, and 20 with diabetes). All patients had been admitted at least twice in the preceding year, had their disease for at least 2 years, and were between the ages of 12 and 18. The control group consisted of 100 adolescents, matched for age and socioeconomic status, from local schools. All subjects completed a questionnaire compiled from the Beck Depression Inventory (BDI), the Rosenberg Scale of Self-Esteem, and the McCutcheon Life Events Checklist. Adolescents with chronic disease had higher depression scores (p less than 0.001) and lower self-esteem (p less than 0.001) than their healthy age-matched controls. There was no statistically significant difference in life events between the chronic disease and control groups. Depression, self-esteem, and life events did not differ significantly among the three disease groups. These findings suggest a need for intervention strategies to address depression and low self-esteem in adolescents with chronic disease.

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.

The Pathophysiology of Amenorrhea in the Adolescent

Menstrual irregularity is a common occurrence during adolescence, especially within the first 2–3 years after menarche. Prolonged amenorrhea, however, is not normal and can be associated with significant medical morbidity, which differs depending on whether the adolescent is estrogen‐deficient or estrogen‐replete. Estrogen‐deficient amenorrhea is associated with reduced bone mineral density and increased fracture risk, while estrogen‐replete amenorrhea can lead to dysfunctional uterine bleeding in the short term and predispose to endometrial carcinoma in the long term. In both situations, appropriate intervention can reduce morbidity. Old paradigms of whom to evaluate for amenorrhea have been challenged by recent research that provides a better understanding of the normal menstrual cycle and its variability. Hypothalamic amenorrhea is the most prevalent cause of amenorrhea in the adolescent age group, followed by polycystic ovary syndrome. In anorexia nervosa, exercise‐induced amenorrhea, and amenorrhea associated with chronic illness, an energy deficit results in suppression of hypothalamic secretion of GnRH, mediated in part by leptin. Administration of recombinant leptin to women with hypothalamic amenorrhea has been shown to restore LH pulsatility and ovulatory menstrual cycles. The use of recombinant leptin may improve our understanding of the pathophysiology of hypothalamic amenorrhea in adolescents and may also have therapeutic possibilities.

Reversibility of Growth stunting in early onset anorexia nervosa: A prospective study

PURPOSE To evaluate the growth of premenarchal patients with anorexia nervosa. METHODS Growth parameters were measured semi-annually in 16 subjects with anorexia nervosa until 1 year post-menarche. RESULTS Despite the accelerated growth that followed nutritional rehabilitation, the patients did not achieve their genetic height potential.