illness. However, anorexia nervosa is a severe psychiatric disorder, and those who remain ill have high rates of psychiatric comorbidity and are at risk for premature death. Diagnostic migration appears to be common between AN-R to AN-B/P and AN-B/P to bulimia nervosa. Little is known about the course and outcome of bulimia nervosa among adolescents, but among adults, bulimia nervosa is a chronic relapsing condition with a 50% recovery rate and a low mortality rate.

The most notable medical complications of anorexia nervosa result from malnutrition. Subcutaneous tissue is lost, muscle wastes, and patients display sunken cheeks and prominence of bony protuberances. Body temperature is usually low and patients often wear multiple layers of clothing to keep warm. The hands and feet may be cold and blue (acrocyanosis); the skin may be pale, dry, and yellow in color. Fine downy hair (lanugo) may be present over the arms, back, and abdomen. Scalp hair is dry, listless, and brittle and there may be evidence of hair loss. Resting pulse and blood pressure are both low, and dizziness and fainting may occur upon standing, as a result of changes in pulse and blood pressure. There may be generalized muscle weakness.

In anorexia nervosa, life-threatening complications include electrolyte disturbances and cardiac arrhythmias. Patients may present with dehydration and abnormal serum levels of sodium, potassium, chloride, carbon dioxide, and blood urea nitrogen. Electrolyte disturbances are more likely in those who are vomiting or abusing laxatives or diuretics. Hyponatremia (low sodium levels) can occur in those who drink excessive amounts of water to either satisfy hunger urges or falsely elevate body weight prior to a medical visit. Water intoxication with hyponatremia can cause seizures, coma, and death. Serum phosphorus levels may be normal on presentation but may drop upon refeeding, and hypophosphatemia may play a role in the development of cardiac arrhythmias and sudden unexpected death seen in the “refeeding syndrome” (Kohn, Golden, & Shenker, 1998).

Resting pulse rates among patients with anorexia nervosa may be as low as 30–40 beats per minute (Palla & Litt, 1988) and systolic and diastolic blood pressures are low. Within the first 4 days of hospitalization, 60%–85% of patients demonstrate orthostatic pulse changes on stand

ing (Shamim, Golden, Arden, Filiberto, & Shenker, 2003). Electrocardiographic (EKG) abnormalities have been noted in up to 75% of hospitalized adolescent patients (Palla & Litt, 1988; Galetta et al., 2002). A prolonged QTc interval, one type of EKG abnormality, is of particular concern because it appears to precede ventricular arrhythmias and sudden death in patients hospitalized with anorexia nervosa (Isner, Roberts, Heymsfield, & Yager, 1985). A pericardial effusion (fluid around the heart) can develop in very malnourished patients (Silverman & Krongrad, 1983). Mitral valve prolapse has been reported in patients with anorexia nervosa (Johnson, Humphries, Shirley, Mazzoleni, & Noonan, 1986; Meyers, Starke, Pearson, & Wilken, 1986), but the apparent prolapse is reversible with weight restoration, whereas true prolapse is a permanent degeneration of the mitral valve (Schocken, Holloway, & Powers, 1989). Congestive heart failure does not usually occur in the starvation phase and is more likely to occur during refeeding (Powers, 1982).

Bloating and constipation are frequent complaints of patients with anorexia nervosa and reflect delayed gastric emptying and decreased intestinal motility. Liver enzymes are elevated in 4%–38% of patients with anorexia nervosa (Mickley, Greenfeld, Quinlan, Roloff, & Zwas, 1996; Palla & Litt, 1988; Sherman, Leslie, Goldberg, Rybczynski, & St. Louis, 1994). Cholesterol levels may be high but most frequently are normal (Arden, Weiselberg, Nussbaum, Shenker, & Jacobson, 1990; Boland, Beguin, Zech, Desager, & Lambert, 2001; Mehler, Lezotte, & Eckel, 1998). Serum carotene levels may be elevated in

13%–62% of cases and may lead to a yellowish discoloration of the skin (Sherman et al., 1994; Boland et al., 2001). The cause of the high serum carotene levels is not clear but is thought to be a combination of increased dietary intake of pigmented vegetables such as carrots and derangements of hepatic conversion of beta-carotene to vitamin A. In contrast to other forms of malnutrition, serum albumin levels are usually normal in anorexia nervosa. Rapid weight loss is associated with gallstone formation. With malnutrition, the metabolic rate slows down as an adaptive response to starvation. In anorexia nervosa, measured resting energy expenditure may be 65%–70% of predicted values (Schebendach et al., 1995). Consequently, in the malnourished state, caloric requirements are lower. With nutritional rehabilitation, metabolic recovery occurs over a 4-to 6-week period and caloric requirements increase dramatically (Schebendach, Golden, Jacobson, Hertz, & Shenker, 1997).

Suppression of the bone marrow occurs frequently in anorexia nervosa, resulting in low white blood cell, red blood cell, and platelet counts. Leukopenia (low white blood cell count) has been reported in one to two thirds of patients with anorexia nervosa and is thought to be secondary to bone marrow suppression (Palla & Litt, 1988; Sharp & Freeman, 1993). Despite the low white blood cell count, there does not appear to be an increased risk of infection. Once a bacterial infection is present, however, low complement levels may prolong the course of the infection. All hematologic abnormalities are reversed with nutritional rehabilitation.

The major neurological complications of eating disorders are seizures and cerebral atrophy, found on computed tomography (CT) and magnetic resonance imaging (MRI) scans (Enzmann & Lane, 1977; Golden et al., 1996; Katzman et al., 1996; Nussbaum, Shenker, Marc, & Klein, 1980). Muscle weakness and a peripheral neuropathy can also occur. Neuropsychological testing has demonstrated impairment of attention, concentration, and memory, with deficits in visuospatial ability (Kingston, Szmukler, Andrewes, Tress, & Desmond, 1996). Although the ventricular enlargement and white matter changes revert to normal after weight restoration (Golden et al., 1996; Katzman, Zipursky, Lambe, & Mikulis, 1997), the gray-matter volume deficits and regional blood flow disturbances may persist. It may be that these changes predate the illness (Golden et al., 1996; Gordon, Lask, Bryant-Waugh, Christie, & Timimi, 1997; Katzman et al., 1997). Similarly, some but not all of the cognitive deficits improve with weight restoration (Kingston et al., 1996).

Adolescents who develop anorexia nervosa prior to the completion of growth can exhibit growth retardation and short stature. Patients are shorter than expected (Nussbaum, Baird, Sonnenblick, Cowan, & Shenker, 1985) and growth stunting may even be the presenting feature (Modan-Moses et al., 2003; Root & Powers, 1983). Growth retardation is more likely to occur in adolescent boys because boys grow, on average, for 2 years longer than girls. In girls, growth is almost complete by menarche, which occurs at an average age of 12.4 years in the United States (Chumlea et al., 2003). Catch-up growth can occur with nutritional rehabilitation, but even with intervention, these adolescents may not reach their genetic height potential (Lantzouni, Frank, Golden, & Shenker, 2002).

Hypothalamic dysfunction is evidenced by amenorrhea (loss of menses) as well as disturbances in satiety, difficulties with temperature regulation, and decreased ability to concentrate urine (Mecklenberg, Loriaux, Thompson, Andersen, & Lipsett, 1976). There is activation of the hypothalamic–adrenal axis with high levels of serum cortisol. Clinically, patients with anorexia nervosa have symptoms that look very much like those seen in hypothyroidism (dry yellow skin, low heart rate, low metabolic rate, amenorrhea, and constipation). Disturbances in thyroid function tests resolve with improved nutrition and should not be treated with thyroid hormone replacement.

Pubertal delay is frequently found among patients who develop anorexia nervosa prior to the completion of puberty (Palla & Litt, 1988; Russell, 1985). Amenorrhea is a cardinal feature of anorexia nervosa, caused by a combination of malnutrition, increased exercise, emotional stress, low body weight, and decreased stores of body fat. Pituitary and ovarian hormones controlling menstruation are all low and the uterus

and ovaries shrink in size (Golden & Shenker, 1992). In most instances, amenorrhea is associated with weight loss, but in approximately 20% of cases loss of menses may precede significant weight loss (Golden et al., 1997). Weight gain is usually accompanied by restoration of normal hypothalamic–pituitary–ovarian function and resumption of spontaneous menses, but in many cases amenorrhea may be prolonged.

Provided weight is restored and menses are regular, the ability to conceive should be normal. Persistence of low body weight and weight control behaviors, however, may be associated with infertility (Bates, Bates, & Whitworth, 1982). A recent study found that women who had a history of anorexia nervosa in the past had pregnancy rates similar to those of healthy controls and were no more likely to have received treatment for infertility (Bulik, Sullivan, Fear, Pickering, & Dawn, 1999). The women with a history of anorexia nervosa, however, were more likely to have a miscarriage, presumably because they continued with inappropriate weight-control behaviors during pregnancy.

The most serious complication of prolonged amenorrhea and a low estrogen state is osteopenia, a substantial reduction in bone mass. In anorexia nervosa, osteopenia may occur after a relatively short duration of illness (Bachrach, Guido, Katzman, Litt, & Marcus, 1990; Grinspoon et al., 2000). Osteopenia is related to a combination of poor nutrition, low body weight, estrogen deficiency, excessive exercise, and high levels of cortisol in the blood stream. The degree of osteopenia in anorexia nervosa is more severe than that seen in women with other conditions associated with amenorrhea and a low estrogen state. This finding suggests that in addition to estrogen deficiency, nutritional factors play an important role (Grinspoon et al., 1999).

Adolescence is a critical time for bone mass acquisition. Approximately 60% of peak bone mass is accrued during the adolescent years, and there is very little net gain in bone mass after 2 years following menarche (Bonjour, Theintz, Buchs, Slosman, & Rizzoli, 1991; Golden & Shenker, 1992; Katzman et al., 1991; Theintz et al., 1992). Whether a young woman will develop osteoporosis in later life depends not only on the rate of bone loss in adulthood but also on the amount of bone present at skeletal maturity, often referred to as “peak bone mass.” Multiple studies have shown that peak bone mass is achieved toward the end of the second decade of life (Bonjour et al., 1991; Faulkner et al., 1996; Katzman et al., 1991; Southard et al., 1991). A woman who develops anorexia nervosa during adolescence will not reach her peak bone mass, thus she will be at increased risk of developing fractures. Because of the lower peak bone mass, the increased fracture risk may persist for years after recovery from anorexia nervosa. Recent studies have demonstrated that more than 90% of adolescents and young adults with anorexia nervosa have reduced bone mass at one or more skeletal sites (Golden, 2003; Grinspoon et al., 2000). Osteopenia that occurs in adolescence may not be completely reversible (Rigotti, Neer, Skates, Herzog, & Nussbaum, 1991; Soyka et al., 2002). Weight gain is associated with some improvement in bone mineral density, but levels do not return to normal (Bachrach, Katzman, Litt, Guido, & Marcus, 1991). A recent study conducted on women who had been in recovery from anorexia nervosa for an average of 21 years found that bone mineral density of the hip remained lower than that of controls, and a relatively high percentage of patients reported a history of pathologic bone fractures (Hartman et al., 2000). Although there are no proven therapies and estrogen has been shown to be ineffective, recent studies have shown that insulin-like growth factor-1 (IGF-1), a nutritionally dependent hormone, may prevent bone loss (Grinspoon, Thomas, Miller, Herzog, & Kilbanski, 2002).

For patients with bulimia nervosa, fluctuations in body weight can be observed, and reflect cycles of dehydration, electrolyte disturbances, and water retention associated with vomiting and abuse of laxatives and diuretics. Massive swelling of the hands and feet can occur among those who abruptly discontinue the use of laxatives or diuretics. Examination of the hands may reveal calluses or scars over the knuckles or skin of the dominant hand (Russell's sign), which are

caused by abrasions by the teeth during self-induced vomiting.

Hypokalemia, a reduced level of potassium in the blood, is the most frequently found significant electrolyte disturbance in patients who vomit or use laxatives or diuretics. Hypokalemia can be associated with life-threatening cardiac arrhythmias, and a low serum potassium level should be carefully corrected. Periods of caloric restriction result in episodes of bradycardia and vital sign instability, although not to the same degree as that seen in patients with anorexia nervosa.

Ipecac, a medication used to induce vomiting after accidental poisoning, is abused by some patients with bulimia nervosa. Ipecac contains the alkaloid emetine, which is toxic to both skeletal and cardiac muscle, and excessive intake may cause muscle weakness, congestive heart failure, and cardiac arrest. Ipecac use is cumulative and ipecac abuse can be a cause of sudden death among adolescents with bulimia nervosa (Schiff et al., 1986).

Enlargement of the parotid and salivary glands occurs in 10% to 30% of patients with bulimia nervosa and is thought to be secondary to binge eating and vomiting (Ogren, Huerter, Pearson, Antonson, & Moore, 1987). Erosion of the dental enamel is most evident on the lingual aspects of the anterior teeth and is caused by the gastric acid. Recurrent vomiting leads to gastroesophageal reflux, esophagitis, tears of the esophagus, and, less frequently, esophageal rupture. Small tears may be evidenced by blood-stained vomiting. Esophageal rupture is a catastrophic event and is usually fatal. Esophagitis is associated with epigastric or retrosternal chest pain and warrants treatment.

The goals of medical management of patients with eating disorders are acute medical stabilization, normalization of eating behaviors, and reversal of medical complications. For patients with anorexia nervosa, weight restoration is an important goal of treatment and is usually associated with improvements in mood and eating disorder symptoms.