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Eating disorders: Epidemiology, pathogenesis, clinical features, and course of illness Author Sara F Forman, MD Section Editor Joel

Yager, MD Deputy Editor David Solomon, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Dec !" . # This topic last updated: Sep $, !" . INTROD !TION % Many aspects o& the 'nited States culture display an obsession with weight loss. (omen)s maga*ines typically have a cover highlighting a story about weight management, dieting hints, or how to tighten speci&ic muscle groups. Models and actors display an unattainable level o& thinness. Some athletes relentlessly pursue a leaner body &or per&ormance enhancement. +ur culture)s obsession to achieve lower weight conveys an unavoidable message to maturing adolescents. According to the !!, Youth -is. /ehavior Survey, 0$ percent o& adolescent girls believed that they were overweight and 1! percent were attempting to lose weight. 2n the 0! days be&ore 3uestioning, 4 percent o& adolescent girls reported that they had tried vomiting or had ta.en la5atives to help control their weight. 6he epidemiology, pathogenesis, and clinical &eatures o& eating disorders are reviewed here. 6reatment and outcomes o& eating disorders7 medical complications o& eating disorders and their management7 evaluation &or medical complications and criteria &or hospitali*ation7 and the re&eeding syndrome in anore5ia nervosa are discussed separately. 8See 9Eating disorders: 6reatment and outcome9.; 8See 9Anore5ia nervosa in adults and adolescents: Medical complications and their management9.; 8See 9/ulimia nervosa and binge eating disorder in adults: Medical complications and their management9.; 8See 9Anore5ia nervosa in adults: Evaluation &or medical complications and criteria &or hospitali*ation to manage these complications9.; 8See 9Anore5ia nervosa in adults and adolescents: 6he re&eeding syndrome9.;

DE"INITION# % According to the American <sychiatric Association)s Diagnostic and Statistical Manual, Fourth Edition, 6e5t -evision 8DSM=2>=6-;, eating disorders include ?"@: Anore5ia nervosa /ulimia nervosa Eating disorders not otherwise speci&ied

$nore%ia nervosa % 6he DSM=2>=6- criteria &or anore5ia nervosa include re&usal to maintain body weight at or above a minimally normal weight &or age and height, intense &ear o& gaining

weight or becoming &at despite being underweight, distorted perception o& body weight and shape, and amenorrhea 8table "; ?"@. 6he diagnosis is discussed separately. 8See 9Anore5ia nervosa in adults: Diagnosis, associated clinical &eatures, and assessment9, section on )Diagnostic criteria) and 9Anore5ia nervosa in adults: Diagnosis, associated clinical &eatures, and assessment9, section on )Di&&erential diagnosis).; &ulimia nervosa % 6he DSM=2>=6- criteria &or bulimia nervosa include recurrent episodes o& binge eating and inappropriate compensatory behavior to prevent weight gain, occurring on average at least two times per wee. &or three months 8table ; ?"@. 6he diagnosis is discussed separately. 8See 9/ulimia nervosa in adults: Alinical &eatures, diagnosis, and assessment9, section on )Diagnosis) and 9/ulimia nervosa in adults: Alinical &eatures, diagnosis, and assessment9, section on )Di&&erential diagnosis).; Eating disorder not otherwise specified % DSM=2>=6- also includes a de&inition &or Eating Disorder Bot +therwise Speci&ied 8ED=B+S; ?"@. 6his category includes patients with clearly aberrant eating patterns and weight management habits who do not meet the criteria &or anore5ia nervosa or bulimia nervosa. 6he most notable prototypes are binge eating disorder, night eating syndrome, sleep related eating disorder, and purging disorder. &inge'eating disorder % According to research criteria, binge=eating disorder is de&ined as eating an amount o& &ood in a discrete period o& time that is de&initely larger than most people would eat in a similar period o& time under similar circumstances ?"@. 6hese episodes occur at least twice a wee. &or at least si5 months. Episodes o& binge eating are associated with a lac. o& control and with distress over the eating. Additional in&ormation about the de&inition o& binge= eating disorder, as well as the epidemiology, treatment planning, and use o& cognitive=behavior therapy are discussed separately. 8See 9/inge=eating disorder: +verview o& treatment in adults9 and 9/inge=eating disorder: Aognitive=behavioral therapy 8A/6;9.; E(IDE)IOLO*+ % 6rends in the epidemiology o& eating disorders are di&&icult to assess because o& changes in the diagnostic criteria over time, and because detection by sel&=report may not be reliable in an illness characteri*ed by secrecy and denial ? @. Most studies report increased prevalence over the past $! years ?0@, although trends over the past "! years are debated. +ne study among college students in Aali&ornia noted a decrease in bingeCpurge behaviors &rom the "D4!s to the "DD!s ?E@. Fowever, most clinicians believe that increased numbers o& eating disordered patients are presenting to their practices. 6he li&etime prevalence o& anore5ia nervosa in women is estimated to be !.0 to " percent ?$@. -ates &or men are signi&icantly lower. Data &rom the Bational Aomorbidity -eplication survey indicate a li&etime prevalence o& !.D and !.0 percent &or women and men respectively ?1@. Data &rom a Finnish birth cohort study suggest a higher li&etime prevalence 8 . percent;, with inclusion o& untreated cases identi&ied by screening ?,@.

/ulimia nervosa is now diagnosed using more stringent criteria in the DSM=2> than in earlier editions o& the DSM. 6his, combined with the shorter length o& time that this illness has been recogni*ed, clouds interpretation o& epidemiologic data. <revalence rates o& " to ".$ percent o& women have been reported ?1,4@. -ates &or younger adolescents are generally lower than those &or college students. ED=B+S occurs in appro5imately 0 to $ percent o& women between the ages o& "$ and 0! in (estern countries ?D@. Eating disorders have become more common among minority culture groups as these groups become assimilated into American society ?"!@. 6he estimated li&etime prevalence o& bulimia nervosa is " to 0 percent and &or anore5ia nervosa is !.$ percent ?"@. Many more have disordered eating and meet criteria &or ED=B+S. 6here are two pea.s o& the onset &or anore5ia nervosa, at ages "E and "4, though patients may present &rom late childhood through adulthood. 6he epidemiology o& binge=eating disorder is discussed separately. 8See 9/inge=eating disorder: +verview o& treatment in adults9, section on )Epidemiology).; )ales with eating disorders % More males sought treatment &or eating disorders in the "DD!s than in the "D4!s ?""@. 2t is unclear whether this re&lects an increase in prevalence or that males are see.ing treatment more o&ten. 6wo studies have &ound that male and &emale anore5ia nervosa patients have similar &amily histories o& eating disorders ?" ,"0@. ($T,O*ENE#I# % 6here is no consensus regarding the causes o& eating disorders. A combination o& genetic, biological, psychological, &amily, environmental, and social &actors probably contribute to developing an eating disorder. An an5ious or per&ectionistic individual may e5perience decreased sel&=esteem or sel&=control because o& predisposing &actors 8eg, biology, &amily history, traumatic events; and then use dieting behavior or weight loss to provide a sense o& stability or control ?"E@. A number o& &actors have been noted to be associated with the development o& eating disorders: 2n one study, a history o& dieting was the most important predictor o& a new eating disorder in adolescent children ?"$@. Ahildhood preoccupation with a thin body and social pressure about weight are associated with the development o& binge eating disorders in adolescence ?"1@. Sports and artistic endeavors in which leanness is emphasi*ed 8eg, ballet, running, or wrestling; and sports in which scoring is partly subGective 8eg, s.ating or gymnastics; are associated with a higher incidence o& eating disorders. Young women with restrictive eating disorders and amenorrhea have been re&erred to as having the 9&emale athlete triad,9 which consists o& an eating disorder, amenorrhea, and osteoporosis ?",@. 8See 9Amenorrhea and in&ertility associated with e5ercise9.;

Studies con&lict about the association o& eating disorders and se5ual abuse. +ne study reported an association between childhood se5ual abuse and bulimia nervosa, but not anore5ia nervosa ?"4@.

A role &or genetics in the pathogenesis o& eating disorders is supported by studies that &ound that young women whose &irst degree relatives have eating disorders were at a si5= to ten=&old increased ris. &or developing an eating disorder ?"D@. Mono*ygotic twins have a higher rate o& concordance &or eating disorders compared with di*ygotic twins ? !, "@. 6here is also a higher prevalence o& a&&ective disorders ? @ and alcoholism ? 0@ in &irst=degree relatives o& patients with eating disorders. Hin.age analysis studies have &ound a susceptibility locus &or bulimia nervosa on chromosome "!p ? E@ and &or anore5ia nervosa on chromosome "p ? $@. <sychiatric problems are common in patients with eating disorders, including a&&ective disorders, an5iety disorders, obsessive=compulsive disorder, and personality disorders, tobacco and other substance abuse ? , 1@. Adult women with eating disorders appear to have had higher rates o& obsessive=compulsive personality traits in childhood ? ,@. Alcohol problems are more prevalent among those with bulimia nervosa than among patients with restrictive anore5ia nervosa ? 0@. Family distress o& any .ind can be a signi&icant &actor in the development o& an eating disorder. Bo strong empirical data support a particular &amily prototype that enhances the development o& eating disorders. Family characteristics associated with eating disorders may include high perceived parental e5pectations &or achievement and appearance, &amilies who have di&&iculties managing con&lict, poor communication style 8particularly related to &eelings;, enmeshment and, less &re3uently, estrangement between &amily members, devaluation o& the mother or the maternal role, and marital tension. Families struggling with an eating disorder o&ten have di&&iculties responding positively to the changing physical and emotional needs o& their adolescent. As with other psychiatric disorders, in &amilies that are highly critical o& the patient 8so=called Ihigh e5pressed emotionJ &amilies; outcomes are less &avorable ? 4@. Role of the central nervous system % Beurotransmitters may have a role in the pathogenesis o& anore5ia nervosa. Decreased levels o& the neurotransmitter norepinephrine may partially account &or the bradycardia and hypotension seen with starvation ? D@. Serotonin plays a role in the brain)s appetite and satiety centers and may account &or some neuropsychiatric changes and loss o& appetite ?0!@. +ne study, &or e5ample, &ound that serotonin metabolite levels were high in anorectic patients a&ter weight restoration ?0"@. Stimulation o& serotonin 8$=F6E; receptors in the brain reward center o& mice reduced their eating drive7 these receptors also mediate the anorectic e&&ect o& the 9club drug9 ecstasy in mice, suggesting a possible path &or the addictive aspect o& anore5ia nervosa ?0 @. M-2 studies have shown brain changes in patients with anore5ia nervosa, including decreased volumes in the gray and white matter with increased ASF volume ?00@. Another report &ound that the grey matter volumes did not entirely normali*e and cerebrospinal &luid volume remained

signi&icantly increased compared with controls a&ter weight recovery ?0E@. 2n comparison, white matter did not signi&icantly di&&er &rom controls a&ter weight recovery. 6he signi&icance o& these &indings is unclear. (RE#ENT$TION $ND #!REENIN* $nore%ia nervosa % 6he core &eatures o& anore5ia nervosa are an abnormally low body weight, intense &ear o& gaining weight, distorted perception o& body weight and shape, and amenorrhea ?"@. 6he clinical &eatures o& anore5ia nervosa are discussed separately. 8See 9Anore5ia nervosa in adults: Diagnosis, associated clinical &eatures, and assessment9, section on )Associated clinical &eatures) and 9Anore5ia nervosa in adults: Diagnosis, associated clinical &eatures, and assessment9, section on )Diagnostic criteria).; &ulimia nervosa % 6he core &eatures o& bulimia nervosa are binge eating 8ie, eating an amount o& &ood that is de&initely larger than most people would eat under similar circumstances; and inappropriate compensatory behavior to prevent weight gain ?"@. 6he prototypic se3uence o& behavior in bulimia nervosa consists o& caloric restriction, binge eating, and sel&=induced vomiting ?0$@. 6he clinical &eatures o& bulimia nervosa are discussed separately. 8See 9/ulimia nervosa in adults: Alinical &eatures, diagnosis, and assessment9, section on )Alinical &eatures) and 9/ulimia nervosa in adults: Alinical &eatures, diagnosis, and assessment9, section on )Aomorbid psychopathology).; #creening tools % A number o& other instruments have been developed to identi&y patients with eating disorders. Some are long and not ideally suited &or screening in a primary care setting. At least two shorter instruments have been developed and, although neither has been e5tensively validated, may help identi&y patients who need &urther evaluation ?01,0,@. (e suggest the SA+FF 3uestionnaire, which consists o& &ive 3uestions ?01,04@: Do you ma.e yoursel& #ic. because you &eel uncom&ortably &ullK Do you worry you have lost !ontrol over how much you eatK Fave you recently lost more than One stone 8"E pounds or 1.0$ .g; in a three month periodK Do you believe yoursel& to be "at when others say you are too thinK (ould you say that "ood dominates your li&eK

A second short tool, the Eating disorder Screen &or <rimary care 8ES<;, has also been evaluated as a screening tool &or eating disorders ?0,@: Are you satis&ied with your eating patternsK 8Bo is abnormal; Do you ever eat in secretK 8Yes is abnormal; Does your weight a&&ect the way you &eel about yoursel&K 8Yes is abnormal; Fave any members o& your &amily su&&ered with an eating disorderK 8Yes is abnormal;

Do you currently su&&er with or have you ever su&&ered in the past with an eating disorderK 8Yes is abnormal;

6he original study describing the SA+FF reported that a 9yes9 to two or more 3uestions was associated with a sensitivity and speci&icity o& "!! and 4,.$ percent &or the diagnosis o& an eating disorder ?01@. A subse3uent report that proposed and evaluated the ES< &ound that two abnormal responses to the ES< had a sensitivity and speci&icity o& "!! and ," percent, and that the sensitivity and speci&icity o& SA+FF was lower 8,4 and 44 percent, respectively; ?0,@. Further validation o& both o& these instruments is needed in broader populations. 6he Eating Attitudes 6est 8EA6; is one o& the most widely used sel&=report eating disorder instruments. 6he 1=item version has an accuracy rate o& at least D! percent when screening patients &or the presence o& a DSM=2> eating disorder, using a cuto&& score o& ! 8table 0; ?0D@. 6he <rimary Aare Evaluation o& Mental Disorders <atient Fealth Luestionnaire is a brie& instrument that both screens &or and provides a categorical DSM=2> diagnosis &or bulimia nervosa, as well as depressive, an5iety, alcohol, and somato&orm disorders ?E!@. 2t was speci&ically designed &or use in primary care, is &ully sel&=administered by the patient, has good diagnostic validity overall 8sensitivity ,$ percent, speci&icity D! percent;, e5cellent diagnostic validity &or eating disorders 8sensitivity 4D percent, speci&icity D1 percent;, and the median physician time to review the results is one to two minutes 8table E;. Additional in&ormation about assessment o& patients with bulimia nervosa is discussed separately. 8See 9/ulimia nervosa in adults: Alinical &eatures, diagnosis, and assessment9, section on )Assessment).; )EDI!$L E-$L $TION $nore%ia nervosa % All patients with anore5ia nervosa should be evaluated &or medical complications 8table $; ?"!,E"@. 6he complications and their signs and symptoms are secondary to caloric restriction and weight loss. 6he evaluation should include a history, physical e5amination, and laboratory testing. 6he evaluation &or medical complications and criteria &or hospitali*ation to manage these complications are discussed separately. 8See 9Anore5ia nervosa in adults: Evaluation &or medical complications and criteria &or hospitali*ation to manage these complications9.; &ulimia nervosa % All patients with bulimia nervosa should be evaluated &or medical complications ?"!,E"@. 6he complications and their signs and symptoms are secondary to persistent purging. 6he evaluation should include a history, physical e5amination, and laboratory testing. 6he evaluation &or medical complications and criteria &or hospitali*ation to manage these complications are discussed separately. 8See 9/ulimia nervosa and binge eating disorder in adults: Medical complications and their management9 and 9Eating disorders: 6reatment and outcome9, section on )Fospitali*ation).;

)EDI!$L !O)(LI!$TION# % Many medical complications can occur during starvation or persistent purging ?"!,E"=E0@. $nore%ia nervosa % Aomplications o& anore5ia nervosa include myocardial atrophy, mitral valve prolapse, pericardial e&&usion, bradycardia, &unctional hypothalamic amenorrhea, antenatal and postpartum problems, osteoporosis, gastroparesis, and constipation 8table $;. 2n addition, growth disturbance can occur in adolescents. Medical complications o& anore5ia nervosa and their management are discussed separately. 8See 9Anore5ia nervosa in adults and adolescents: Medical complications and their management9.; &ulimia nervosa and .inge eating disorder % Aomplications o& bulimia nervosa include dehydration, hypo.alemia, menstrual irregularities, Mallory=(eiss syndrome, ipecac=induced myopathy, and erosion o& dental enamel. Electrocardiogram changes can occur in both disorders. Medical complications o& bulimia nervosa and binge eating disorder, and their management are discussed separately. 8See 9/ulimia nervosa and binge eating disorder in adults: Medical complications and their management9.; !O R#E O" ILLNE## $nore%ia nervosa % +utcome studies have &ocused upon anore5ia nervosa ?EE,E$@. +ne review &ound that appro5imately $! percent o& patients have good outcomes 8de&ined by return o& menses and weight gain;, $ percent have intermediate outcomes, and $ percent have a poor outcome ?E$@. A number o& patients with anore5ia nervosa have a bulimic phase during their recoveries. <oor outcomes are associated with later age at onset o& the eating disorder, longer duration o& the illness, lower minimal weight ?EE@, and lower percent body &at a&ter weight restoration ?E1@. +verall, 0 to ,! percent recover &ully at ! years o& &ollow=up7 those who do not may have increased psychiatric comorbidity ?" ,E,,E4@. <sychological variables are important predictors o& outcome. 2n one &our=year &ollow=up study, strong &ears o& maturing predicted a poor outcome in patients with restricting anore5ia nervosa, while low sel&=esteem was associated with a poor outcome in those with bulimia nervosa ?ED@. Signi&icant items predicting better outcome in another report in patients with anore5ia nervosa were insight and success&ul interpersonal relationships7 mood and personality disorders were negative predictors ?$!@. <atients with anore5ia nervosa who recover o&ten su&&er persisting psychiatric problems. 2n a case=control study o& ,! &emale patients, those who no longer met criteria &or anore5ia nervosa still mani&ested relatively low body weight and cognitive &eatures 8per&ectionism and cognitive restraint; o& the disorder, as well as high rates o& li&etime comorbid maGor depression, alcohol dependence, and an5iety disorders ?$"@.

&ulimia nervosa % +ne study that &ollowed ",0 women with bulimia nervosa &ound that the number o& patients who continued to meet the &ull criteria &or bulimia nervosa declined as the duration o& &ollow=up increased ?$ @. Fowever, recurrent binging and purging behaviors persisted over appro5imately "! years o& &ollow=up in 0! percent. Substance abuse and long duration o& the disorder were associated with poor outcome. )ORT$LIT+ % Several studies suggest that all cause mortality is elevated in patients with eating disorders ?$0@. $nore%ia nervosa % Anore5ia nervosa appears to be associated with increased mortality: A meta=analysis o& E studies conducted between "D ! and "D4! 80,!!1 patients &ollowed &or a median o& 4 years; &ound that all cause mortality was !.$1 percent per year ?$E@. Medical complications o& anore5ia nervosa accounted &or appro5imately $! percent o& the deaths and suicide accounted &or $ percent. Feterogeneity was not reported. A review o& &our studies 811! patients; &ound that all cause mortality was $ times the e5pected value 8based upon general population mortality statistics;, and suicide deaths were 0 times greater ?$0@. A subse3uent prospective study o& "01 patients &ollowed &or a median o& nine years &ound that all cause mortality was " times greater compared with the general population 8standardi*ed mortality ratio "".1, D$M A2 $.$= ".0;, and that completed suicide was $, times greater in patients with anore5ia nervosa 8standardi*ed mortality ratio $1.D, D$M A2 "$.0="E$.,; ?$$@. Duration o& anore5ia nervosa and severity o& alcohol use disorder were associated with an increased ris. o& all cause mortality. Fowever, most mortality studies &or anore5ia nervosa were per&ormed at re&erral centers that speciali*ed in treatment resistant patients who were o&ten hospitali*ed, and mortality rates may be lower outside o& these centers. A retrospective community study e5amined mortality in !4 patients with relatively mild anore5ia nervosa 8most had never seen a psychiatrist and &ew had been hospitali*ed &or the disorder; over a median &ollow=up o& !.E="."; ?$1@. &ulimia nervosa % /ulimia nervosa may possibly be associated with increased mortality: A retrospective study o& D!1 patients who were &ollowed &or a mean o& "D years through the 'nited States Bational Death 2nde5 &ound that all cause mortality was appro5imately twice as high, compared with the general population 8standardi*ed mortality ratio ".1, D$M A2 "."= . ;, and that the rate o& suicide was appro5imately seven times greater 8standardi*ed mortality ratio 1.$, D$M A2 .4=" .4; ?$,@ A retrospective study o& D1 patients &ollowed &or E to "$ years &ound that all cause mortality was nine times the e5pected value ?$0,$4@ years7 all cause mortality &or patients and &or the general population were comparable 8standardi*ed mortality ratio !.,, D$M A2

Fowever, in a prospective study o& ""! patients with bulimia nervosa, mortality &or patients and mortality &or the general population were comparable 8standardi*ed mortality ratio ".0, D$M A2 !.!=,. ; ?$$@. Eating disorder not otherwise specified % Eating disorders not otherwise speci&ied may be associated with increased mortality. A retrospective study o& 4! patients with an eating disorder not otherwise speci&ied, who were &ollowed &or a mean o& ", years through the 'nited States Bational Death 2nde5, &ound that all cause mortality was nearly twice as high compared with the general population 8standardi*ed mortality ratio ".4, D$M A2 ".0= .$;, and that the rate o& suicide was nearly &our times greater 8standardi*ed mortality ratio 0.D, D$M A2 "."="!.!; ?$,@ IN"OR)$TION "OR ($TIENT# % 'p6oDate o&&ers two types o& patient education materials, I6he /asicsJ and I/eyond the /asics.J 6he /asics patient education pieces are written in plain language, at the $th to 1th grade reading level, and they answer the &our or &ive .ey 3uestions a patient might have about a given condition. 6hese articles are best &or patients who want a general overview and who pre&er short, easy=to=read materials. /eyond the /asics patient education pieces are longer, more sophisticated, and more detailed. 6hese articles are written at the "!th to "
th

grade reading level and are best &or patients who want in=depth in&ormation and

are com&ortable with some medical Gargon. Fere are the patient education articles that are relevant to this topic. (e encourage you to print or e=mail these topics to your patients. 8You can also locate patient education articles on a variety o& subGects by searching on Ipatient in&oJ and the .eyword8s; o& interest.; /asics topics 8see 9<atient in&ormation: Anore5ia nervosa 86he /asics;9 and 9<atient in&ormation: /ulimia nervosa 86he /asics;9; # ))$R+ $ND RE!O))END$TION# A DSM=2>=6- diagnosis o& anore5ia nervosa re3uires each o& the criteria listed in the table 8table ";. 6he two subtypes o& anore5ia nervosa are restricting and binge eatingCpurging. 8See )Anore5ia nervosa) above and 9Anore5ia nervosa in adults: Diagnosis, associated clinical &eatures, and assessment9, section on )Diagnostic criteria).; 6he DSM=2>=6- diagnostic criteria &or bulimia nervosa include binge eating 8consuming a large amount o& &ood in a discrete period o& time; and inappropriate compensatory behavior to prevent weight gain, both occurring on average at least two times per wee. &or three months 8table ;. 8See )/ulimia nervosa) above and 9/ulimia nervosa in adults: Alinical &eatures, diagnosis, and assessment9, section on )Diagnosis).; 2n DSM=2>=6-, binge=eating disorder is characteri*ed by episodes o& eating an amount o& &ood in a discrete period o& time that is de&initely larger than most people would eat in a similar period o& time under similar circumstances. 6hese episodes occur at least twice a wee. &or at least si5 months. Episodes o& binge eating are associated with a lac. o&

control and with distress over the eating. 8See )/inge=eating disorder) above and 9/inge= eating disorder: +verview o& treatment in adults9.; 6he estimated li&etime prevalence o& anore5ia nervosa in women is !.D and in men !.0 percent. 6he estimated li&etime prevalence o& bulimia nervosa in women is " to ".$ percent. 6he estimated li&etime prevalence o& binge=eating disorder in women is 0.$ and men .! percent. 8See )Epidemiology) above and 9/inge=eating disorder: +verview o& treatment in adults9, section on )Epidemiology).; 6here is no consensus regarding the causes o& eating disorders. A combination o& genetic, biological, psychological, &amily, environmental, and social &actors probably contribute to developing an eating disorder. 8See )<athogenesis) above.; 6he SA+FF is a &ive=item sel&=report measure that screens &or eating disorders. +ther screening tools include the ES<, EA6, and <rimary Aare Evaluation o& Mental Disorders <atient Fealth Luestionnaire. 8See )Screening tools) above.; All patients with anore5ia nervosa and bulimia nervosa should be evaluated &or medical complications. 6he evaluation should that include a history, physical e5amination, and laboratory testing. 8See 9Anore5ia nervosa in adults: Evaluation &or medical complications and criteria &or hospitali*ation to manage these complications9 and 9/ulimia nervosa and binge eating disorder in adults: Medical complications and their management9, section on )Medical evaluation) and 9Eating disorders: 6reatment and outcome9, section on )Fospitali*ation).; Many medical complications can occur during starvation andCor persistent purging. Aomplications o& anore5ia nervosa include myocardial atrophy, mitral valve prolapse, pericardial e&&usion, bradycardia, &unctional hypothalamic amenorrhea, antenatal and postpartum problems, osteoporosis, gastroparesis, and constipation 8table $;. Aomplications o& bulimia nervosa include dehydration, hypo.alemia, Mallory=(eiss syndrome, ipecac=induced myopathy, and erosion o& dental enamel. Electrocardiogram changes can occur in both disorders. 8See 9Anore5ia nervosa in adults and adolescents: Medical complications and their management9 and 9/ulimia nervosa and binge eating disorder in adults: Medical complications and their management9.; Appro5imately $! percent o& patients with anore5ia nervosa have good outcomes 8de&ined by return o& menses and weight gain;, $ percent have intermediate outcomes, and $ percent have a poor outcome. +utcome in bulimia nervosa is poor in appro5imately 0! percent. 8See )Aourse o& illness) above.; All cause mortality appears to be elevated in eating disorders. <atients with anore5ia nervosa &re3uently die &rom medical complications o& the disorder or by suicide. 8See )Mortality) above.; 'se o& 'p6oDate is subGect to the Subscription and Hicense Agreement. RE"EREN!E# ". American <sychiatric Association. Diagnostic and Statistical Manual o& Mental Disorders, Fourth Edition, 6e5t -evision, American <sychiatric Association, (ashington, DA, !!!.

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(a.eling A. Epidemiology o& anore5ia nervosa. <sychiatry -es "DD17 1 :0. Hucas A-, /eard AM, +)Fallon (M, Nurland H6. $!=year trends in the incidence o& anore5ia nervosa in -ochester, Minn.: a population=based study. Am J <sychiatry "DD"7 "E4:D",. Featherton 6F, Bichols <, Mahamedi F, Neel <. /ody weight, dieting, and eating disorder symptoms among college students, "D4 to "DD . Am J <sychiatry "DD$7 "$ :"1 0. Foe. F(, van Foe.en D. -eview o& the prevalence and incidence o& eating disorders. 2nt J Eat Disord !!07 0E:040. Fudson J2, Firipi E, <ope FO Jr, Nessler -A. 6he prevalence and correlates o& eating disorders in the Bational Aomorbidity Survey -eplication. /iol <sychiatry !!,7 1":0E4. Nes.i=-ah.onen A, Foe. F(, Susser ES, et al. Epidemiology and course o& anore5ia nervosa in the community. Am J <sychiatry !!,7 "1E:" $D. Fairburn AO, /eglin SJ. Studies o& the epidemiology o& bulimia nervosa. Am J <sychiatry "DD!7 "E,:E!". <utu.ian M. 6he &emale triad. Eating disorders, amenorrhea, and osteoporosis. Med Alin Borth Am "DDE7 ,4:0E$. American <sychiatric Association. 6reatment o& patients with eating disorders,third edition. American <sychiatric Association. Am J <sychiatry !!17 "10:E. /raun DH, Sunday S-, Fuang A, Falmi NA. More males see. treatment &or eating disorders. 2nt J Eat Disord "DDD7 $:E"$. Strober M, Freeman -, Morrell (. 6he long=term course o& severe anore5ia nervosa in adolescents: survival analysis o& recovery, relapse, and outcome predictors over "!="$ years in a prospective study. 2nt J Eat Disord "DD,7 :00D. Strober M, Freeman -, Hampert A, et al. Males with anore5ia nervosa: a controlled study o& eating disorders in &irst=degree relatives. 2nt J Eat Disord !!"7 D: 10. Oarner, DM, Oar&in.el, <E. Fandboo. o& treatment &or eating disorders, nd ed, Ouil&ord <ress, Bew Yor. "DD,. <atton OA, Sel*er -, Ao&&ey A, et al. +nset o& adolescent eating disorders: population based cohort study over 0 years. /MJ "DDD7 0"4:,1$. McNnight 2nvestigators. -is. &actors &or the onset o& eating disorders in adolescent girls: results o& the McNnight longitudinal ris. &actor study. Am J <sychiatry !!07 "1!: E4. Battiv A, Agostini -, Drin.water /, Yeager NN. 6he &emale athlete triad. 6he inter= relatedness o& disordered eating, amenorrhea, and osteoporosis. Alin Sports Med "DDE7 "0:E!$. Sanci H, Ao&&ey A, +lsson A, et al. Ahildhood se5ual abuse and eating disorders in &emales: &indings &rom the >ictorian Adolescent Fealth Aohort Study. Arch <ediatr Adolesc Med !!47 "1 : 1". (oodside D/. A review o& anore5ia nervosa and bulimia nervosa. Aurr <robl <ediatr "DD$7 $:1,. Nendler NS, MacHean A, Beale M, et al. 6he genetic epidemiology o& bulimia nervosa. Am J <sychiatry "DD"7 "E4:"1 ,. Strober M. Family=genetic studies o& eating disorders. J Alin <sychiatry "DD"7 $ Suppl:D. Fer*og D/, Bussbaum NM, Marmor AN. Aomorbidity and outcome in eating disorders. <sychiatr Alin Borth Am "DD17 "D:4E0. Falmi NA, Ec.ert E, Marchi <, et al. Aomorbidity o& psychiatric diagnoses in anore5ia nervosa. Arch Oen <sychiatry "DD"7 E4:," . /uli. AM, Devlin /, /acanu SA, et al. Signi&icant lin.age on chromosome "!p in &amilies with bulimia nervosa. Am J Fum Oenet !!07 , : !!. Orice DE, Falmi NA, Fichter MM, et al. Evidence &or a susceptibility gene &or anore5ia nervosa on chromosome ". Am J Fum Oenet !! 7 ,!:,4,. Nrug 2, 6reasure J, Anderluh M, et al. <resent and li&etime comorbidity o& tobacco, alcohol and drug use in eating disorders: a European multicenter study. Drug Alcohol Depend !!47 D,:"1D. Anderluh M/, 6chanturia N, -abe=Fes.eth S, 6reasure J. Ahildhood obsessive= compulsive personality traits in adult women with eating disorders: de&ining a broader eating disorder phenotype. Am J <sychiatry !!07 "1!: E . van Furth EF, van Strien DA, Martina HM, et al. E5pressed emotion and the prediction o& outcome in adolescent eating disorders. 2nt J Eat Disord "DD17 !:"D.

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<ir.e NM. Aentral and peripheral noradrenalin regulation in eating disorders. <sychiatry -es "DD17 1 :E0. Naye (F. <ersistent alterations in behavior and serotonin activity a&ter recovery &rom anore5ia and bulimia nervosa. Ann B Y Acad Sci "DD,7 4",:"1 . Naye (F, Owirtsman FE, Oeorge D6, Ebert MF. Altered serotonin activity in anore5ia nervosa a&ter long=term weight restoration. Does elevated cerebrospinal &luid $= hydro5yindoleacetic acid level correlate with rigid and obsessive behaviorK Arch Oen <sychiatry "DD"7 E4:$$1. Jean A, Aonductier O, Manri3ue A, et al. Anore5ia induced by activation o& serotonin $= F6E receptors is mediated by increases in AA-6 in the nucleus accumbens. <roc Batl Acad Sci ' S A !!,7 "!E:"100$. Nat*man DN, Hambe EN, Mi.ulis DJ, et al. Aerebral gray matter and white matter volume de&icits in adolescent girls with anore5ia nervosa. J <ediatr "DD17 " D:,DE. Hambe EN, Nat*man DN, Mi.ulis DJ, et al. Aerebral gray matter volume de&icits a&ter weight recovery &rom anore5ia nervosa. Arch Oen <sychiatry "DD,7 $E:$0,. Howe, M-. Dietary restraint and overeating. 2n: Eating Disorders and +besity, , Fairburn, AO, /rowell, ND 8Eds;, 6he Ouil&ord <ress, Bew Yor. !! . p.44. Morgan JF, -eid F, Hacey JF. 6he SA+FF 3uestionnaire: assessment o& a new screening tool &or eating disorders. /MJ "DDD7 0"D:"E1,. Aotton MA, /all A, -obinson <. Four simple 3uestions can help screen &or eating disorders. J Oen 2ntern Med !!07 "4:$0. Fill HS, -eid F, Morgan JF, Hacey JF. SA+FF, the development o& an eating disorder screening 3uestionnaire. 2nt J Eat Disord !"!7 E0:0EE. Mint* H/, +)Falloran MS. 6he Eating Attitudes 6est: validation with DSM=2> eating disorder criteria. J <ers Assess !!!7 ,E:E4D. Spit*er -H, Nroen.e N, (illiams J/. >alidation and utility o& a sel&=report version o& <-2ME=MD: the <FL primary care study. <rimary Aare Evaluation o& Mental Disorders. <atient Fealth Luestionnaire. JAMA "DDD7 4 :",0,. Eating Disorders: Aore 2nterventions in the 6reatment o& and Management o& Anore5ia Bervosa, /ulimia Bervosa and -elated Eating Disorders. Bational 2nstitute &or Alinical E5cellence, Alinical Ouideline D. http:CCguidance.nice.org.u. 8Accessed on December , !"!;. Mehler, <S, /irmingham, HA, Arow, SJ, Jahraus, J<. Medical complications o& eating disorders. 2n: 6he 6reatment o& Eating Disorders: A Alinical Fandboo., Orilo, AM, Mitchell, JE 8Eds;, 6he Ouil&ord <ress, Bew Yor. !"!. p.11. Falmi, N. Eating disorders: Anore5ia nervosa, bulimia nervosa, and obesity. 2n: 6he American <sychiatric <ublishing 6e5tboo. o& <sychiatry, Fi&th Edition, Fales, -E, Yudo&s.y, SA, Oabbard O+ 8Eds;, American <sychiatric <ublishing, 2nc., (ashington, DA !!4. p.D,". Oolden BF, Nat*man DN, Nreipe -E, et al. Eating disorders in adolescents: position paper o& the Society &or Adolescent Medicine. J Adolesc Fealth !!07 00:ED1. Steinhausen FA. 6he outcome o& anore5ia nervosa in the !th century. Am J <sychiatry !! 7 "$D:" 4E. Mayer HE, -oberto AA, Olaso&er D-, et al. Does percent body &at predict outcome in anore5ia nervosaK Am J <sychiatry !!,7 "1E:D,!. 6heander S. +utcome and prognosis in anore5ia nervosa and bulimia: some results o& previous investigations, compared with those o& a Swedish long=term study. J <sychiatr -es "D4$7 "D:ED0. -ussell, OF. 6he prognosis o& eating disorders, Springer=>erlag, Bew Yor. "DD". p."D4. van der Fam 6, van Strien DA, van Engeland F. <ersonality characteristics predict outcome o& eating disorders in adolescents: a E=year prospective study. Eur Ahild Adolesc <sychiatry "DD47 ,:,D. Saccomani H, Savoini M, Airrincione M, et al. Hong=term outcome o& children and adolescents with anore5ia nervosa: study o& comorbidity. J <sychosom -es "DD47 EE:$1$. Sullivan <F, /uli. AM, Fear JH, <ic.ering A. +utcome o& anore5ia nervosa: a case= control study. Am J <sychiatry "DD47 "$$:D0D.

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Neel <N, Mitchell JE, Miller N/, et al. Hong=term outcome o& bulimia nervosa. Arch Oen <sychiatry "DDD7 $1:10. Farris EA, /arraclough /. E5cess mortality o& mental disorder. /r J <sychiatry "DD47 ",0:"". Sullivan <F. Mortality in anore5ia nervosa. Am J <sychiatry "DD$7 "$ :"!,0. Neel <N, Dorer DJ, Eddy N6, et al. <redictors o& mortality in eating disorders. Arch Oen <sychiatry !!07 1!:",D. NorndPr&er S-, Hucas A-, Suman >J, et al. Hong=term survival o& patients with anore5ia nervosa: a population=based study in -ochester, Minn. Mayo Alin <roc !!07 ,4: ,4. Arow SJ, <eterson A/, Swanson SA, et al. 2ncreased mortality in bulimia nervosa and other eating disorders. Am J <sychiatry !!D7 "11:"0E . <atton OA. Mortality in eating disorders. <sychol Med "D447 "4:DE,. 6opic !D0 >ersion "0.!

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&ulimia nervosa and .inge eating disorder in adults: )edical complications and their management Authors James E. Mitchell, MD Ahristie Qun.er, <hD, A<F, AFES Section Editor Joel Yager, MD Deputy Editor David Solomon, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Dec !" . # This topic last updated: Bov 0!, !" . INTROD !TION % Medical complications and symptoms o& poor health are common in patients with bulimia nervosa 8/B; and binge eating disorder 8/ED; ?", @. As an e5ample, an epidemiologic study &ound that somatic symptoms such as shortness o& breath, chest pain, Goint pain, gastrointestinal problems, menstrual problems, and headache occurred in signi&icantly more patients with either /B or /ED compared with patients who had no psychiatric disorder. 6he medical complications o& /B and /ED and their management are reviewed here. 6he epidemiology, pathogenesis, clinical &eatures, treatment, and outcome are discussed separately, as are the medical complications o& anore5ia nervosa.

8See 9Eating disorders: Epidemiology, pathogenesis, clinical &eatures, and course o& illness9.; 8See 9Eating disorders: 6reatment and outcome9.; 8See 9/inge=eating disorder: +verview o& treatment in adults9.; 8See 9Anore5ia nervosa in adults and adolescents: Medical complications and their management9.;

DE"INITION# &ulimia nervosa % /B is mar.ed by episodes o& binge eating. 2n addition, there are inappropriate compensatory behaviors to prevent weight gain, including sel&=induced vomiting7 misuse o& la5atives, diuretics, or enemas7 e5cessive e5ercise7 &asting7 or strict diets 8table "; ?0@. 6he de&inition o& /B is discussed separately. 8See 9Eating disorders: Epidemiology, pathogenesis, clinical &eatures, and course o& illness9, section on )/ulimia nervosa).; &inge eating disorder % /ED is characteri*ed by episodes o& binge eating, without the inappropriate compensatory behaviors that are seen in bulimia nervosa. 6he de&inition o& /ED is discussed separately. 8See 9/inge=eating disorder: +verview o& treatment in adults9, section on )De&inition o& binge=eating disorder 8/ED;).; )EDI!$L E-$L $TION % 6he medical evaluation should pursue symptoms and signs o& the medical complications described below. 2n addition, all patients with /B should receive a basic panel o& laboratory tests, and additional tests as indicated by &indings &rom the history and physical e5amination. <atients with medical complaints due to /B o&ten attempt to hide their eating disorder &rom clinicians ?E@. 6he medical evaluation o& patients with /ED is the same as it is &or patients in the general population, and is guided by the medical status o& the patient. )edical history % 6he most common medical symptoms o& /B are lethargy, irregular menses, abdominal pain and bloating, and constipation ?E,$@. (hysical e%amination % (ithin the conte5t o& a complete physical e5amination, .ey portions include weight and height7 vital signs including heart rate, blood pressure both supine and standing, and temperature7 s.in7 oropharyngeal7 abdominal and neurologic e5amination 8to loo. &or other causes o& weight loss or vomiting, eg, abdominal or central nervous system mass;. !ommon physical signs % Aommon signs o& /B are ? ,1@: 6achycardia Fypotension 8R D! mm Fg systolic; Serosis 8dry s.in; <arotid gland swelling Erosion o& dental enamel

+ther signs that are o&ten present include hair loss, edema, and scarring or calluses on the dorsum o& the hand. La.oratory assessment % 6ests should be guided by the symptoms and physical &indings. Haboratory tests indicated &or all patients with /B include ?,@: Serum electrolytes /lood urea nitrogen Serum creatinine Aomplete blood count including di&&erential Hiver &unction tests 'rinalysis

Severely ill patients with /B warrant additional tests ?,@: Serum calcium, magnesium, and phosphorous Electrocardiogram 8EAO;

For patients with suspected pancreatitis, clinicians should chec. serum amylase, &ractionated &or salivary gland isoen*yme ?,@. <ersistent amenorrhea should be investigated with luteini*ing hormone, &ollicle=stimulating hormone, prolactin, and beta=human chorionic gonadotropin. Suspected la5ative abuse can be assessed by chec.ing stool or urine &or bisacodyl, emodin, aloe=emodin, and rhein. Bo speci&ic laboratory tests are indicated &or patients with /ED, unless they are obese and obesity=associated comorbidity is suspected. )EDI!$L !O)(LI!$TION# O" & LI)I$ NER-O#$ % 6he medical complications that occur in patients with /B a&&ect many organ systems, and depend upon the method and &re3uency o& purging, ie, sel&=induced vomiting or misuse o& la5atives, diuretics, or enemas. 6reatment &or each complication includes discontinuation o& purging. *astrointestinal % Oastrointestinal complications include ? ,$,,="!@: <arotid and submandibular 8salivary; gland hypertrophy, with pu&&y or swollen chee.s Hoss o& gag re&le5 Esophageal dysmotility Abdominal pain and bloating Feme=stained emesis Mallory=(eiss syndrome 8esophageal tears; Esophageal rupture 8/oerhaavesT syndrome; Oastroesophageal re&lu5 disease 8OE-D; Oastric dilation

Diarrhea and malabsorption Steatorrhea <rotein=losing gastroenteropathy Fypo.alemic ileus Aolonic dysmotility Aonstipation Melanosis coli Aathartic colon <ancreatitis

6he di&&erential diagnosis o& vomiting and right upper 3uadrant pain includes biliary disease ? @. An ultrasound can e5clude the presence o& gallstones. 8See 9<athogenesis, clinical &eatures, and diagnosis o& acute cholecystitis9 and 9Approach to the patient with incidental gallstones9.; Swollen parotid and submandibular glands usually do not re3uire treatment, and should decrease in si*e over several months. For patients with pain due to swollen glands, treatment includes applying hot pac.s to the glands and suc.ing on hard candy ? @. 2& this is not success&ul, then oral pilocarpine should be prescribed to stimulate salivary &low, at a dose o& $ mg two to three times per day. /ilateral gland enlargement due to purging should be distinguished &rom unilateral parotitis, which involves a bacterial in&ection and re3uires antibiotic medication. Diagnosis and management o& OE-D are discussed separately. 8See 9Alinical mani&estations and diagnosis o& gastroesophageal re&lu5 in adults9 and 9Medical management o& gastroesophageal re&lu5 disease in adults9.; Management o& diarrhea and malabsorption are discussed separately. 8See 9+verview o& the treatment o& malabsorption9.; Diagnosis and treatment o& protein=losing gastroenteropathy are discussed separately. 8See 9<rotein=losing gastroenteropathy9.; Management o& ileus secondary to hypo.alemia is discussed separately. 8See )-enal and electrolytes) below and 9Alinical mani&estations and treatment o& hypo.alemia9.; 6reatment options &or constipation include si5 to eight glasses o& water per day7 e5ercise7 and "! gram o& &iber per day, one to three tablespoons o& polyethylene glycol powder per day, or lactulose ? ,$@. <atients should avoid high=dose, bul.ing, &iber=containing la5atives or stimulant la5atives that contain senna, cascara, or bisacodyl, which will worsen constipation. 2n addition, patients who misuse la5atives in an e&&ort to lose weight should be educated that la5atives act upon the colon, a&ter caloric absorption has occurred. Additional in&ormation about the evaluation and management o& chronic constipation is discussed separately. 8See 9Etiology and evaluation o& chronic constipation in adults9 and 9Management o& chronic constipation in adults9.;

Acute pancreatitis may develop in patients who abuse alcohol ? @. A review o& $ studies &ound that among patients with /B, 0 percent met criteria &or alcohol abuse andCor dependence ?""@. 2n addition, pancreatitis can occur in patients with /B who do not abuse alcohol or who have been abstinent &rom alcohol &or many years7 the etiology is unclear and not necessarily related to vomiting ?" @. 6reatment o& pancreatitis is discussed separately. 8See 96reatment o& acute pancreatitis9.; )allory'/eiss syndrome % Force&ul vomiting may cause longitudinal mucosal lacerations in the distal esophagus and pro5imal stomach. <atients with the Mallory=(eiss syndrome may vomit bright red blood along with gastric contents. A complete rupture o& the esophageal wall 8/oerhaavesT syndrome; is very rare, but e5tremely dangerous. 6he rupture usually appears in the lower chest, causes intense pain and contamination o& the mediastinum and lungs, and re3uires immediate emergency care ? @. 6he diagnosis and treatment o& the Mallory=(eiss syndrome and /oerhaaveTs syndrome are discussed separately. 8See 9Mallory=(eiss syndrome9 and 9/oerhaave)s syndrome: E&&ort rupture o& the esophagus9.; Renal and electrolytes % 6he most common complications o& /B related to electrolyte imbalances include 8table ; ? ,,@: Dehydration Fypo.alemia Fypochloremia Metabolic al.alosis 8because o& volume contraction;

+ther complications include hypomagnesemia, hypophosphatemia, and hyponatremia ?$@. -outine screening detects an electrolyte abnormality in "! percent o& patients with /B ?$@. Fypo.alemia may cause muscle wea.ness, cardiac arrhythmias, and impair renal &unction ?$,4@. 6o correct an electrolyte abnormality, it is usually su&&icient to discontinue the purging behavior ?$@. Management o& electrolyte abnormalities is discussed separately: 8See 9Evaluation o& the patient with hypo.alemia9.; 8See 9Alinical mani&estations and treatment o& hypo.alemia9.; 8See 9Evaluation and treatment o& hypomagnesemia9.; 8See 9Diagnosis and treatment o& hypophosphatemia9.; 8See 96reatment o& metabolic al.alosis9.;

Dehydration % Dehydration can cause volume depletion, with symptoms o& di**iness and orthostasis. 6reatment includes replenishing intravascular &luid with saline ? @. For inpatients, intravenous normal saline should be used. Aaution must be e5ercised to avoid edema. For outpatients, salt cubes in water or chic.en broth should be ingested, starting with three cups per day and increasing as needed. 6he goal is to increase output o& lighter=colored urine, increase

venous Gugular pressure, and eliminate postural changes in pulse and blood pressure. Additional in&ormation about rehydration is discussed separately. 8See 9Maintenance and replacement &luid therapy in adults9, section on )-eplacement &luid therapy).; !ardiac % Aardiac complications are rare in patients with /B ? @. Aomplications include ?,@: Fypotension and orthostasis Sinus tachycardia <alpitations Edema Electrocardiogram 8EAO; changes Depressed S6 segment L6 prolongation (idened L-S comple5 2ncreased <=wave amplitude 2ncreased <- interval Supraventricular and ventricular ectopic rhythm 6orsade de pointes

Arrhythmia

2& L6 prolongation is present, clinicians should avoid medications that prolong the L6 c interval 8table 0; ?,@. 8See 9Ac3uired long L6 syndrome9.; 6reatment o& cardiovascular complications includes correcting any associated cause, eg, hypo.alemia or volume depletion. 2& complications persist despite corrective measures, or i& complications are accompanied by chest pain, shortness o& breath, di**iness, or loss o& consciousness, a cardiology consult should be obtained. Ipecac'induced myopathy % 2pecac syrup is an over=the=counter emetic that some patients with /B ingest to induce vomiting. A case series o& 11" patients with /B &ound that nine percent chronically abused ipecac ?"0@. Ahronic use damages muscle cells including the myocardium, which may lead to cardiomyopathy. !ardiac % +ne component o& ipecac is emetine, which accumulates in cardiac muscle cells and is to5ic ?D,"E@. Emetine is eliminated &rom the body slowly, and has been detected in urine 1! days a&ter chronic use. Signs and symptoms o& cardioto5icity include precordial chest pain, dyspnea, hypotension, supraventricular tachycardia, atrial premature contractions, &lattened or inverted 6 waves, prolonged L6 and <- intervals, ventricular tachycardia and &ibrillation, cardiac &ailure, pericardial e&&usion, pulmonary congestion, and cardiac arrest.

Small, chronic doses have caused cumulative, &atal to5icity in a &ew patients. 6he lethal chronic dose is not .nown. Absorption o& emetine is enhanced in patients who become re&ractory to the emetic e&&ects o& the drug during chronic misuse. <atients suspected o& chronic ipecac abuse should receive a cardiology consult. 6reatment includes discontinuation o& ipecac and supportive care ?D@. Bo speci&ic antidote or pharmacologic antagonist &or the cardioto5ic e&&ects o& emetine e5ists, and patients may die despite intensive care. -ecovery may be prolonged 8eg, months; because emetine is slowly eliminated &rom the body. #0eletal muscle % Ahronic abuse o& ipecac may damage s.eletal muscle ?,,D,"0@. Symptoms include generali*ed wea.ness, especially in the nec. and pro5imal muscles o& the e5tremities7 myalgia and tenderness7 hypore&le5ia7 slurred speech7 dysphagia7 and di&&iculty with tas.s re3uiring muscular activity 8eg, climbing stairs;. 2pecac=induced myopathy is associated with elevated liver &unction tests, nonspeci&ic abnormalities on an electromyographic 8EMO; recording, and abnormal muscle biopsy. Bormal muscular activity is slowly restored &ollowing discontinuation o& ipecac. Ahronic ipecac abuse and subse3uent cardiac myopathy are both discussed separately. 8See )2pecac=induced myopathy) above.; Endocrine % Endocrine complications o& /B involve the reproductive and s.eletal systems, and there may be an association between /B and diabetes. Severe complications can occur in patients with /B and comorbid diabetes ?$@. 6he most common endocrine complication involves the reproductive system. Among 4 women treated &or /B, menstrual irregularities were present in E$ percent at pretreatment and in 0" percent at " month &ollow=up ?"$@. /y contrast, an epidemiologic study o& E!0 healthy, premenopausal women aged "4 to 0D years &ound that $ percent had anovulatory menstrual cycles ?"1@. Signs and symptoms o& reproductive system complications include impaired &ertility, spotty and scanty menstrual periods, oligomenorrhea, or amenorrhea ?,@. /B may be associated with diabetes. An epidemiologic study o& E1$" &emales, treated in primary care or obstetric gynecology settings, &ound that diabetes was present in signi&icantly more patients with /B compared with patients who had no eating disorder 8D versus 0 percent; ?",@. Aonversely, a meta=analysis o& eight case=controlled studies 8,E4 &emale patients with type " diabetes and "$4, nondiabetic &emales; &ound that the prevalence o& /B was signi&icantly higher in the diabetic patients compared with the nondiabetic patients 8".,0 versus !.1D percent; ?"4@. Diagnosis and treatment o& diabetes are discussed separately. 8See 9+verview o& medical care in adults with diabetes mellitus9.; +steopenia and osteoporosis may be more common in /B, particularly in patients who have had previous episodes o& anore5ia nervosa ?,@. Management o& osteoporosis is discussed separately. 8See 9Evaluation and treatment o& premenopausal osteoporosis9.;

6hyroid &unction is usually normal in /B ? @. A study compared ,$ bulimic women with 1E healthy control women and &ound similar values &or &ree 6E and &ree 60 ?"D@. Dental % Oastric acid in vomitus so&tens and erodes dental enamel, which may cause sensitivity to hot and cold temperatures in &ood and drin.s ? @. Some patients e5hibit decalci&ication o& the teeth 8perimylolysis;, particularly on the lingual, palatal, and posterior occlusal sur&aces ?E@. 6eeth may also become discolored, and caries and gum disease may occur. Enamel loss can be reduced by instructing patients to wash out their mouth a&ter vomiting, gargle with ba.ing soda in water to al.alini*e their mouth, wait at least 0! minutes be&ore brushing their teeth, and use al.aline toothpaste ? @. Fot and cold &oods and li3uids should be limited as needed to avoid pain. Acidic &oods 8eg, &ruit and yogurt; should also be limited ?$@. Ahewing sugarless gum is recommended to increase salivary &low. 2n addition, a dentist should be consulted &or restorative procedures a&ter purging is controlled. #0in % A nearly pathognomonic dermatologic complication is scarring or calluses on the dorsum o& the hand 8-ussellTs sign7 due to pressure o& the teeth against the s.in while stimulating the gag re&le5 to induce vomiting; 8picture "; ? ,,@. A study o& " ? "@. Sel&=inGurious behavior is common in /B, and patients may show acute or chronic signs o& trauma &rom cuts or burns ?$@. Other % +ther medical complications include &luctuation o& body weight, vitamin de&iciencies, aspiration pneumonitis, and conGunctival hemorrhage ? ,,,D@. )EDI!$L !O)(LI!$TION# O" &IN*E E$TIN* DI#ORDER % <atients with /ED o&ten describe somatic symptoms and dissatis&action with health. Fowever, there is little evidence o& medical complications that can be directly attributed to binge=eating symptoms ?",, study suggests hypercholesterolemia is associated with /ED ? @. , 0@. +ne patients with /B detected this sign in 0! percent ? !@. Serosis, poor s.in turgor, petechia, telogen e&&luvium, and acne may also be seen

An observational study o& $D obese women with a li&etime history o& binge eating and "!, obese women without binge eating compared the prevalence o& sel&=reported hypertension, cardiac problems, diabetes 8type " or ;, osteoarthritis, asthma, visual impairment, or any maGor medical disorder ? 0@. <atients with binge eating reported higher rates o& each disorder, although the di&&erences did not reach statistical signi&icance. An epidemiologic study &ound that Goint pain, headache, gastrointestinal problems, menstrual problems, shortness o& breath, and chest pain each occurred in signi&icantly more patients with /ED than patients without psychiatric disorders ?",@. Fowever, somatic symptoms do not necessarily e3uate with medical complications. Another &inding was that signi&icantly more patients with /ED described their general health as poor or very poor, compared with patients

&ree o& psychiatric disorders 8, versus " percent;, but the association o& /ED with poor health was not signi&icant when the analyses controlled &or comorbid mood disorders. O.esity % Many patients with /ED are obese and su&&er the medical complications associated with obesity ?E,4@. 6he complications o& obesity are discussed separately. 8See 9Fealth ha*ards associated with obesity in adults9.; 2t is not clear i& /ED is associated with medical complications beyond those observed in obese patients ? ,E, 0@. Several studies show higher rates o& gastrointestinal, cardiovascular, pulmonary, and rheumatologic disorders or symptoms in obese patients with /ED compared to obese patients without /ED, but the di&&erences are generally not statistically signi&icant. Dia.etes % /ED does not appear to be associated with diabetes. 2n an observational study, "0E patients with /ED were matched &or age, se5, and body mass inde5 with "0E individuals with no history o& an eating disorder. +ver &ive years o& &ollow=up, the incidence o& new=onset type diabetes was similar &or subGects with and without /ED 8"! versus 4 percent; ? @. Although an epidemiologic study o& patients treated in primary care and obstetric gynecology settings &ound that diabetes was present in signi&icantly more patients with /ED compared with patients who had no eating disorder 81 versus 0 percent;, the comparison did not control &or body mass inde5 ?",@. Most studies indicate that /ED or binge eating do not signi&icantly a&&ect glycemic control in type diabetes ? @. Diagnosis and treatment o& diabetes are discussed separately. 8See 9+verview o& medical care in adults with diabetes mellitus9.; ,ypercholesterolemia % An observational study o& patients with /ED matched &or body mass inde5 with individuals with no eating disorder &ound that hypercholesterolemia occurred in signi&icantly more patients with /ED 80! versus ", percent; ? @.

,O#(IT$LI1$TION % Aertain medical complications re3uire inpatient treatment on an internal medicine, psychiatric, or combined ward. 6he choice depends upon the patientTs medical and psychiatric status, and available resources. Ariteria &or inpatient treatment and principles o& management in this setting are discussed separately. 8See 9Eating disorders: 6reatment and outcome9, section on )Fospitali*ation).; IN"OR)$TION "OR ($TIENT# % 'p6oDate o&&ers two types o& patient education materials, I6he /asicsJ and I/eyond the /asics.J 6he /asics patient education pieces are written in plain language, at the $th to 1th grade reading level, and they answer the &our or &ive .ey 3uestions a patient might have about a given condition. 6hese articles are best &or patients who want a general overview and who pre&er short, easy=to=read materials. /eyond the /asics patient education pieces are longer, more sophisticated, and more detailed. 6hese articles are written at

the "!th to "

th

grade reading level and are best &or patients who want in=depth in&ormation and

are com&ortable with some medical Gargon. Fere are the patient education articles that are relevant to this topic. (e encourage you to print or e=mail these topics to your patients. 8You can also locate patient education articles on a variety o& subGects by searching on Ipatient in&oJ and the .eyword8s; o& interest.; /asics topic 8see 9<atient in&ormation: /ulimia nervosa 86he /asics;9;

# ))$R+ $ND RE!O))END$TION# /B is mar.ed by episodes o& binge eating. 2n addition, there are inappropriate compensatory behaviors to prevent weight gain, including sel&=induced vomiting7 misuse o& la5atives, diuretics, or enemas7 e5cessive e5ercise7 &asting7 or strict diets 8table ";. 8See 9Eating disorders: Epidemiology, pathogenesis, clinical &eatures, and course o& illness9, section on )/ulimia nervosa).; /ED is characteri*ed by episodes o& binge eating, without the inappropriate compensatory behaviors that are seen in bulimia nervosa. 8See 9/inge=eating disorder: +verview o& treatment in adults9, section on )De&inition o& binge=eating disorder 8/ED;).; 6he most common medical symptoms o& /B are lethargy, irregular menses, abdominal pain and bloating, and constipation. 8See )Medical history) above.; (ithin the conte5t o& a complete physical e5amination, .ey portions include weight and height7 vital signs including heart rate, blood pressure both supine and standing, and temperature7 s.in7 oropharyngeal7 abdominal and neurologic e5amination to evaluate &or other causes o& weight loss or vomiting. Aommon signs o& bulimia nervosa are tachycardia, hypotension, 5erosis, parotid gland swelling, and erosion o& dental enamel. 8See )<hysical e5amination) above.; Oastrointestinal complications include parotid and submandibular gland hypertrophy7 loss o& gag re&le57 abdominal pain, bloating and dilatation7 Mallory=(eiss syndrome, gastroesophageal re&lu5 disease 8OE-D;7 diarrhea and malabsorption7 constipation7 and colonic dysmotility. 8See )Oastrointestinal) above.; 6he most common renal and electrolyte complications include dehydration, hypo.alemia, hypochloremia, and metabolic al.alosis. 8See )-enal and electrolytes) above.; Aardiac complications are rare. Aomplications observed in patients with /B include hypotension and orthostasis, sinus tachycardia, palpitations, edema, electrocardiogram changes, and arrhythmia. 8See )Aardiac) above.; 2pecac is used by some patients with /B to induce vomiting, and chronic abuse may cause cardiomyopathy and damage s.eletal muscle. 8See )2pecac=induced myopathy) above and )S.eletal muscle) above.; Endocrine complications o& /B involve the reproductive and s.eletal systems, and there may be an association between /B and diabetes. 8See )Endocrine) above.;

Dental complications o& /B include erosion o& dental enamel, decalci&ication and discoloration o& the teeth, caries, and gum disease. 8See )Dental) above.; Dermatologic complications include scarring or calluses on the dorsum o& the hand 8-ussellTs sign; 8picture ";, 5erosis, poor s.in turgor, petechia, telogen e&&luvium, and acne. 2n addition, patients with sel&=inGurious behavior will show acute or chronic signs o& trauma &rom cuts or burns. 8See )S.in) above.;

<atients with /ED o&ten describe somatic symptoms and dissatis&action with health. Fowever, there is little evidence o& medical complications that can be directly attributed to binge=eating symptoms. 8See )Medical complications o& binge eating disorder) above.;

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'se o& 'p6oDate is subGect to the Subscription and Hicense Agreement. RE"EREN!E# Mitchell JE, Arow S. Medical complications o& anore5ia nervosa and bulimia nervosa. Aurr +pin <sychiatry !!17 "D:E04. Mehler, <S, /irmingham, HA, Arow, SJ, Jahraus, J<. Medical complications o& eating disorders. 2n: 6he 6reatment o& Eating Disorders: A Alinical Fandboo., Orilo, AM, Mitchell, JE 8Eds;, 6he Ouil&ord <ress, Bew Yor. !"!. p.11. American <sychiatric Association. Diagnostic and Statistical Manual o& Mental Disorders, Fourth Edition, 6e5t -evision, American <sychiatric Association, !!!. p.$DE. Mitchell, JE, Arow, SJ. Medical comorbidities o& eating disorders. 2n: 6he +5&ord Fandboo. o& Eating Disorders, Agras, (S 8Eds;, +5&ord 'niversity <ress, Bew Yor. !"!. p. $D. Eating Disorders: Aore 2nterventions in the 6reatment o& and Management o& Anore5ia Bervosa, /ulimia Bervosa and -elated Eating Disorders. Bational 2nstitute &or Alinical E5cellence, Alinical Ouideline D. http:CCguidance.nice.org.u. 8Accessed on December , !"!;. Mehler, <S, Anderson, AE. Eating Disorders: A guide to medical care and complications, nd ed, 6he Johns Fop.ins 'niversity <ress, /altimore, MD !"!. American <sychiatric Association. 6reatment o& patients with eating disorders,third edition. American <sychiatric Association. Am J <sychiatry !!17 "10:E. <omeroy, A, Mitchell, JE, -oerig, J, Arow, S. Medical Aomplications o& <sychiatric 2llness, American <sychiatric <ublishing, 2nc., (ashington, DA !! . American Society o& Fealth=System <harmacists. AFFS Drug 2n&ormation !!4, American Society o& Felath=System <harmacists, American Fospital Formulary Service, /ethesda, MD !!4. p. DD!. Falmi, N. Eating disorders: Anore5ia nervosa, bulimia nervosa, and obesity. 2n: 6he American <sychiatric <ublishing 6e5tboo. o& <sychiatry, Fi&th Edition, Fales, -E, Yudo&s.y, SA, Oabbard O+ 8Eds;, American <sychiatric <ublishing, 2nc., (ashington, DA !!4. p.D,". Folderness AA, /roo.s=Ounn J, (arren M<. Ao=morbidity o& eating disorders and substance abuse review o& the literature. 2nt J Eat Disord "DDE7 "1:". Morris HO, Stephenson NE, Ferring S, Marti JH. -ecurrent acute pancreatitis in anore5ia and bulimia. J+< !!E7 $: 0". Oreen&eld D, Mic.ley D, Luinlan DM, -olo&& <. 2pecac abuse in a sample o& eating disordered outpatients. 2nt J Eat Disord "DD07 "0:E"". 2pecac syrup: Drug in&ormation http:CCuptodate.com 8Accessed on +ctober D, !"!;. Oendall NA, /uli. AM, Joyce <-, et al. Menstrual cycle irregularity in bulimia nervosa. Associated &actors and changes with treatment. J <sychosom -es !!!7 ED:E!D. (aller N, Swan SF, (indham OA, et al. 'se o& urine biomar.ers to evaluate menstrual &unction in healthy premenopausal women. Am J Epidemiol "DD47 "E,:"!,". Johnson JO, Spit*er -H, (illiams J/. Fealth problems, impairment and illnesses associated with bulimia nervosa and binge eating disorder among primary care and obstetric gynaecology patients. <sychol Med !!"7 0":"E$$.

"4. "D. !. ". . 0.

Mannucci E, -otella F, -icca >, et al. Eating disorders in patients with type " diabetes: a meta=analysis. J Endocrinol 2nvest !!$7 4:E",. Monteleone <, Santonastaso <, <annuto M, et al. Enhanced serum cholesterol and triglyceride levels in bulimia nervosa: relationships to psychiatric comorbidity, psychopathology and hormonal variables. <sychiatry -es !!$7 "0E: 1,. Olorio -, Allevato M, De <ablo A, et al. <revalence o& cutaneous mani&estations in !! patients with eating disorders. 2nt J Dermatol !!!7 0D:0E4. Strumia -. Dermatologic signs in patients with eating disorders. Am J Alin Dermatol !!$7 1:"1$. Fudson J2, Halonde JN, Aoit AE, et al. Hongitudinal study o& the diagnosis o& components o& the metabolic syndrome in individuals with binge=eating disorder. Am J Alin Butr !"!7 D":"$14. /uli. AM, Sullivan <F, Nendler NS. Medical and psychiatric morbidity in obese women with and without binge eating. 2nt J Eat Disord !! 7 0 :, .

complications and their management Find <atient <rint Email

$nore%ia nervosa in adults and adolescents: )edical complications and their management Author <hilip Mehler, MD Section Editor Joel Yager, MD Deputy Editor David Solomon, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Dec !" . # This topic last updated: Aug "0, !" . INTROD !TION % Anore5ia nervosa 8AB; is associated with numerous medical complications that are directly attributable to caloric restriction and weight loss ?"@. Some complications are pervasive and one o& them, amenorrhea, is re3uired to diagnose AB in women ? @. Medical complications account &or more than hal& o& all deaths in patients with AB ?0@. A systematic review o& E observational studies 80!!1 patients with AB; &ound that the crude rate o& all=cause mortality was si5 percent ?E@, and a review o& ""D case series 8$$D! patients; &ound a rate o& &ive percent ?$@. Standardi*ed mortality ratios show that the rate o& death in AB is "! to " times greater than the rate in the general population ?1=4@. 6he medical complications o& AB and their management are reviewed here. 6he evaluation &or medical complications and criteria &or hospitali*ation o& patients with AB7 epidemiology, pathogenesis, clinical &eatures, treatment, and outcome o& AB7 re&eeding syndrome7 and medical complications o& bulimia nervosa and binge eating disorder are discussed separately. 8See 9Anore5ia nervosa in adults: Evaluation &or medical complications and criteria &or hospitali*ation to manage these complications9.; 8See 9Eating disorders: Epidemiology, pathogenesis, clinical &eatures, and course o& illness9.; 8See 9Eating disorders: 6reatment and outcome9.; 8See 9Anore5ia nervosa in adults and adolescents: 6he re&eeding syndrome9.; 8See 9/ulimia nervosa and binge eating disorder in adults: Medical complications and their management9.; DI$*NO#I# O" $NORE2I$ NER-O#$ % <atients with AB re&use to maintain a minimally normal body weight o& at least 4$ percent o& that e5pected &or age and height ? @. An alternative and stricter guideline re3uires that the patient have a body mass inde5 8/M2; U",.$ 8calculator "; ?D@. AB is also characteri*ed by intense &ear o& gaining weight and a disturbed perception o& body weight and shape 8table ";. 6here are two subtypes o& AB ? @: -estricting V mar.ed by weight loss through dieting, &asting, and e5cessive e5ercise

/inge eating and purging V mar.ed by episodes o& binge eating and inappropriate compensatory behaviors to prevent weight gain, including sel&=induced vomiting and misuse o& la5atives, diuretics, or enemas

6he clinical &eatures and diagnosis o& AB are discussed separately. 8See 9Eating disorders: Epidemiology, pathogenesis, clinical &eatures, and course o& illness9, section on )Anore5ia nervosa).; 6his topic reviews the medical complications o& the restricting type o& AB. Aomplications due to the binging and purging behaviors are discussed separately within the conte5t o& the medical complications that occur in patients with bulimia nervosa and binge eating disorder. 8See 9/ulimia nervosa and binge eating disorder in adults: Medical complications and their management9.; )EDI!$L E-$L $TION % <atients with the &ood=restricting subtype o& AB should be evaluated &or medical complications 8table ; ?0,"!@. 6he complications and their signs and symptoms can occur in many organ systems. 6he evaluation o& all patients with AB should include a history, physical e5amination and laboratory testing. 6he evaluation &or medical complications o& AB is discussed separately. 8See 9Anore5ia nervosa in adults: Evaluation &or medical complications and criteria &or hospitali*ation to manage these complications9.; *ENER$L (RIN!I(LE# % 6he medical complications o& anore5ia nervosa 8AB; are a direct result o& weight loss and malnutrition ?""," @. Starvation induces protein and &at catabolism that leads to loss o& cellular volume and atrophy o& the heart, brain, liver, intestines, .idneys, and muscles. As an e5ample, muscle wasting, including the myocardium, occurs during starvation in order to provide amino acids &or production o& glucose. 6he number o& organ systems adversely a&&ected increases with the severity o& weight loss 8table ;. 6he reported incidence o& these medical complications varies, depending upon individual predilections and severity o& the current episode o& AB, as reported in cross=sectional studies and case series ?"0,"E@. 6he primary ris. &actors &or developing medical complications in AB are the degree o& weight loss and the chronicity o& the illness ?"0@. 6here are no .nown sociodemographic ris. &actors &or developing complications. 6reatment &or each complication includes nutritional replenishment, and many complications resolve with weight gain ?0@. 6here are no randomi*ed trials that have evaluated the management o& medical complications &rom AB. !$RDIO-$#! L$R % Aardiovascular complications o& anore5ia nervosa 8AB; involve structural ?"$@ and &unctional abnormalities ?"1,",@. #tructural changes % Structural changes include decreased cardiac mass, reduced cardiac chamber volumes, and mitral valve prolapse.

Substantial weight loss in AB is accompanied by atrophy o& cardiac muscle, decreased cardiac mass, and reduced cardiac chamber volumes 8picture "; ?"$@. 6his leads to decreased cardiac output, reduced e5ercise capacity, an attenuated blood pressure response to e5ercise, and subGective &atigue ?",@. Some individuals may also display decreased contractility. Most cardiac changes become clinically signi&icant only when the patient is below 4! percent o& ideal body weight. 6he wea.ened heart muscle generally improves with weight gain, and heart si*e normali*es with clinical recovery over wee.s to months ?"4@. <atients with AB may complain o& chest pain or palpitations, which are o&ten due to mitral valve prolapse. 6he valve prolapses as the patient loses weight because the heart muscle decreases in si*e while the structural tissue that comprises the mitral valve remains the same si*e ?"D@. +ne echocardiography study &ound mitral valve prolapse in ! percent o& patients with AB ?"$@. /y contrast, the Framingham Feart Study &ound an overall prevalence o& .E percent in the general population ? !@. <hysical e5amination in patients with the mitral valve prolapse syndrome o&ten reveals a systolic murmur and Iclic.,J but there are no associated EAO &indings. Alinically signi&icant regurgitation is rare, and there are no .nown cases that re3uired mitral valve surgery ? "@. 6he prolapse generally recedes with weight gain. 6he mitral valve prolapse syndrome is discussed separately. 8See 9Mitral valve prolapse syndrome9 and 9De&inition and diagnosis o& mitral valve prolapse9.; 6here is no evidence o& increased anginal pain in young patients with AB, and autopsy studies do not reveal evidence o& obstructive coronary disease ? @. Although total levels o& cholesterol may be elevated in as many as $! percent o& patients7 this is due to a high level o& cardioprotective FDH and insigni&icant elevations in HDH ? 0@. 6he presumptive cause o& elevated FDH is e5cessive e5ercise and weight loss. An overview o& ris. &actors &or cardiovascular disease and management o& cardiovascular ris. in women are discussed separately. 8See 9+verview o& the ris. e3uivalents and established ris. &actors &or cardiovascular disease9 and 9Determinants and management o& cardiovascular ris. in women9.; <ericardial e&&usion has been reported in adolescents with AB ? E, $@. A study o& " 4 &emale adolescents with AB revealed a pericardial e&&usion in percent 8 D patients;, using two= dimensional Doppler echocardiography ? $@. Bone o& the patients with an e&&usion had a &riction murmur and none had clinical or echocardiographic signs o& cardiac tamponade. 6he e&&usion disappeared within three months o& re&eeding in "4 o& the D 81 percent; patients with an e&&usion at baseline. Diagnosis and treatment o& pericardial e&&usion are discussed separately. 8See 9Diagnosis and treatment o& pericardial e&&usion9.; "unctional changes % Functional cardiovascular changes include bradycardia, hypotension, L6 dispersion, and diminished heart rate variability ?"1,",, 1@. 2n addition, the long L6 syndrome may be seen in some patients, but it is not clear whether AB directly causes the syndrome. 6here are no electrocardiogram 8EAO; &indings speci&ic to AB ? "@. Aside &rom bradycardia, the EAO is o&ten normal. Aase reports describe S6 and 6=wave changes, atrioventricular bloc., or

ventricular arrhythmia, particularly in patients with hypo.alemia or hypomagnesemia ? ,=0"@. An EAO at baseline will screen &or these potential abnormalities. EAO abnormalities should dissipate with weight restoration and correction o& any underlying electrolyte abnormality. An overview o& management o& arrhythmias is discussed separately. 8See 9Arrhythmia management &or the primary care clinician9.; 2ncreased L6 dispersion is another mar.er o& increased arrhythmic ris. in patients with AB, particularly in patients who weigh less than 4! percent o& ideal body weight ?0 =0E@. Bormally, the length o& the L6 interval is similar between each o& the EAO leads. L6 dispersion re&ers to the di&&erence between the ma5imum L6 interval and the minimum L6 interval occurring in any o& the leads on a routine " =lead EAO, and re&lects heterogeneous ventricular depolari*ation. 6he etiology o& increased L6 dispersion in AB is un.nown but may be due to direct inGury o& the myocardium during starvation. <atients with AB may have a two&old or greater increase in L6 dispersion, which correlates with the severity o& their weight loss and reduced metabolic rate. 6he abnormality normali*es with re&eeding. L6 dispersion is discussed separately. 8See 9L6 dispersion: Measurement and interpretation9 and 9L6 dispersion: Alinical applications9.; Aoncerns have been raised that AB causes L6 interval prolongation, which predisposes patients to li&e=threatening ventricular arrhythmias such as torsade de pointes ?0,0$@. Some studies have documented L6 interval prolongation in severe AB ?"1@, which normali*ed a&ter weight gain ?"$,01@. Fowever, other studies have &ound that the L6 interval is usually normal ?0,@. Many authorities thin. that the L6 interval is not inherently prolonged in AB, and that L6 prolongation does not independently cause sudden death in patients with AB ? "@. 6hus, the presence o& a long L6 interval in a patient with AB should prompt a search &or an electrolyte disturbance or the presence o& the congenital long L6 syndrome. 6he long L6 syndrome is discussed separately. 8See 9Ac3uired long L6 syndrome9 and 9Alinical &eatures o& congenital long L6 syndrome9.; 2n patients with AB, abnormal autonomic nervous system &unction appears to diminish heart rate variability ? 1@. Bormally, moment=to=moment &luctuations in heart rate re&lect the underlying stability o& the autonomic nervous system and integration o& sympathetic and parasympathetic &unction. -educed heart rate variability predicts sudden death in patients with heart &ailure, and may also be correlated with an increased incidence o& sudden death in AB, especially in patients who weigh less than 4! percent o& ideal body weight. A decreased rate o& variability suggests that the patient needs a more comprehensive cardiac evaluation. Feart rate variability is discussed separately. 8See 9Feart rate variability: 'ses other than a&ter myocardial in&arction9.; Some patients are hypotensive 8systolic blood pressure RD! mmFg andCor a diastolic blood pressure R$! mmFg; ? "@. +ne study &ound hypotension in "1 percent o& patients with AB ?"0@. Symptoms o& hypotension include &atigue and wea.ness. 2n addition, there may be orthostatic hypotension 8decrease in systolic blood pressure o& W ! mmFg, decrease in diastolic blood pressure o& W"! mmFg, or symptoms o& cerebral hypoper&usion, within two to &ive minutes o& moving &rom a supine position to standing;. Symptoms include lightheadedness upon standing,

wea.ness, and cognitive impairment. +rthostasis may also indicate the need &or hospitali*ation, depending upon the severity ?"!@. Evaluation and treatment o& orthostatic hypotension are discussed separately. 8See 9Mechanisms, causes, and evaluation o& orthostatic and postprandial hypotension9 and 96reatment o& orthostatic and postprandial hypotension9.; &radycardia % /radycardia 8R1! beats per minute; is o&ten &ound in patients with AB, with heart rates as low as $ beats per minute ?0,"0, ",04@. A study o& "E women with AB &ound that the average mean heart rate was 1 beats per minute, and that bradycardia was present in E" percent and hypotension in "1 percent ?"0@. 6he reduced cardiac &unction and use o& energy represent an adaptive, compensatory response to caloric deprivation. 6he cause appears to be increased parasympathetic 8vagal; activity with unchanged sympathetic tone ?0D@. <atients typically describe nonspeci&ic symptoms related to bradycardia, such as &atigue, wea.ness, and lightheadedness. /radycardia is e5pected with AB, and should not, in and o& itsel&, result in therapy directed to increase the heart rate. Although clinicians might &ind com&ort in a normal heart rate, Irelative tachycardiaJ 8pulse o& ,! to "!!; in patients with moderate to severe AB may have more sinister implications ?E!@. A normal heart rate, even i& not strictly in the elevated range 8pulse X"!!;, is probably due to a medication side e&&ect, an5iety, or an impending medical complication, and should be viewed as a warning sign in need o& medical evaluation ?E"@. 6his is especially germane during the early stages o& re&eeding, in which it may be a harbinger o& heart &ailure and the re&eeding syndrome. 8See 9Anore5ia nervosa in adults and adolescents: 6he re&eeding syndrome9, section on )<athogenesis o& the re&eeding syndrome).; +ne clinical issue is deciding what degree o& bradycardia re3uires hospitali*ation &or continuous monitoring o& cardiac &unction with telemetry or treatment in an intensive=care unit. 6here are no studies that have directly addressed this 3uestion in patients with AB. Bearly all authorities agree on the need &or hospitali*ation and telemetry &or any adult patient with a heart rate less than 0! beats per minute. (hether the patient is admitted to an intensive care unit depends upon the presence o& other clinical problems and availability o& resources. 6he American <sychiatric Association practice guideline suggests hospitali*ation &or a heart rate o& less than E! beats per minute ?"!@. /ased upon our clinical e5perience, we suggest telemetry i& the patient has a cardiac rhythm other than sinus bradycardia, or a heart rate o& less than E! beats per minute and hypotension or symptoms o& lightheadedness. /radycardia in patients with AB generally resolves as weight is restored to a level greater than 4! percent o& ideal body weight, or even earlier once a stable pattern o& nutritional replenishment and progressive weight gain ensues ?E @. An overview o& bradycardia is discussed separately. 8See 9Sinus bradycardia9.; *+NE!OLO*I! $ND RE(ROD !TI-E % 6he reproductive system is altered in anore5ia nervosa 8AB;, causing a cascade o& events that results in secondary amenorrhea ?E0@. /y

de&inition, all &emale patients with AB have amenorrhea ? @. 2n contrast, an epidemiologic study o& E!0 healthy, premenopausal women aged "4 to 0D years &ound that $ percent had anovulatory menstrual cycles ?EE@. Aentral nervous system reproductive &unctions are disrupted in AB ?E$,E1@. Bormally, nerve impulses within the hypothalamus trigger the pulsatile secretion o& gonadotropin releasing hormone, which acts upon the pituitary. 6his initiates the release o& luteini*ing hormone and &ollicle=stimulating hormone, which in turn determine the onset o& normal menstrual &unction. 2n patients with AB, secretion o& gonadotropin releasing hormone is reduced, which ultimately prevents ovulation and causes a &unctional hypothalamic amenorrhea. 8See 9Etiology, diagnosis, and treatment o& secondary amenorrhea9, section on )Functional hypothalamic amenorrhea).; (eight loss o& between "! to "$ percent o& normal weight disrupts the menstrual cycle in most women ?E0@. Fowever, amenorrhea may precede weight loss in up to ! percent o& women with AB. 2n addition, rigorous e5ercise in patients with AB contributes to the secondary amenorrhea ?E,,E4@. Aonversely, normal menstrual cycles usually resume with weight gain ?ED@. 6he time course and amount o& weight re3uired &or resumption o& menses has varied among di&&erent studies. A two= year cohort study o& "!! adolescent &emales with AB &ound that menses resumed in a mean average o& nine months, re3uired a weight o& E.$ pounds 8 .g; more than the weight at which menses were lost, and that 41 percent resumed their menses within si5 months o& achieving a weight appro5imately D! percent o& ideal body weight ?ED@. +ther studies support a goal o& attaining D! percent o& ideal body weight in order to restore normal menses ?E0@. Another cohort study &ollowed $1 adolescent &emales with AB and &ound that a return o& menses occurred in 1E percent by one=year &ollow=up ?$!@. +ne study &ound the weight re3uirement &or resumption o& menses varied considerably and was predicted by the weight at which menstruation ceased ?$"@. Amenorrhea persists in about "! to 0! percent o& patients with AB despite weight gain, because o& ongoing abnormal eating behaviors 8binge eating and purging;, e5ercise, or stress ?E0,$ @. For patients distressed by persistent amenorrhea, eventual recovery o& menstrual periods may occur &ollowing psychotherapy. (e do not suggest use o& se5 hormones &or the purpose o& treating amenorrhea in patients with AB. 6he etiology, diagnosis, and treatment o& secondary amenorrhea are discussed separately. 8See 9Etiology, diagnosis, and treatment o& secondary amenorrhea9.; "ertility % <atients with AB may become pregnant despite their amenorrheic state ?$0@. 2n addition, there is a higher rate o& complications o& pregnancy, as well as neonatal complications, in AB ?$E@. Although in&ertility is e5pected in AB due to amenorrhea and decreased libido, patients may nevertheless ovulate and become pregnant ?E0,$0@. Many patients want to avoid pregnancy, and some o& the pregnancies that occur are not planned and lead to an induced abortion. 2n the Borwegian Mother and Ahild Aohort study, an unplanned pregnancy occurred in a signi&icantly

higher percentage o& the 1 patients with AB, compared with the 1",DD4 women with no eating disorder 8$! versus "D percent;. Signi&icantly more patients also had a history o& induced abortion 8 E versus "$ percent;. Fertility is usually restored in patients who recover &rom AB and remain stable ?",$$@. 2& pregnancy does occur, both pregnancy and lactation stress the maternal s.eleton &or minerali*ation o& the &etus and newborn. /ased upon clinical e5perience, clinicians should provide vitamin D and calcium supplementation, and suggest a diet enriched in protein and phosphate. 2n addition, pregnancy in AB is associated with a greater incidence o& complications including miscarriages, premature birth, smaller head circum&erence, and low=birth=weight in&ants, especially i& the disease is active ?$E@. Butrition during pregnancy and pregnancy outcomes in women with eating disorders are discussed separately. 8See 9Butrition in pregnancy9 and 9Eating disorders in pregnant women9, section on )<regnancy outcome).; <atients with AB may conceal their eating disorder when see.ing treatment &or in&ertility ?E0@. +ne study o& 11 women treated in an in&ertility clinic &ound that 4 percent had covert AB ?$1@. Although it is possible &or amenorrheic women to conceive by inducing ovulation using pulsatile gonadotrophin=releasing hormone or gonadotrophins, the presence o& active AB is commonly &elt to be a contraindication &or this type o& in&ertility treatment. ENDO!RINE % <atients with anore5ia nervosa 8AB; have abnormal levels o& several hormones, including low levels o& gonadotropin releasing hormone 8On-F;, luteini*ing hormone 8HF;, &ollicle= stimulating hormone 8FSF;, insulin=li.e growth &actor " 82OF=";, &ree testosterone, triiodothyronine 860;, thyro5ine 86E;, leptin, and antidiuretic hormone 8ADF; ?E$,E1,$,=1"@. 2n addition, there are increased levels o& growth hormone and cortisol. -educed leptin levels correlate with weight, percentage o& body &at, and 2OF=" ?1 ,10@. Amenorrhea in AB may in part be due to reduced leptin ?"@. 8See 9Amenorrhea and in&ertility associated with e5ercise9, section on )Heptin and other peptides).; ,ypothalamus and pituitary % AB disrupts hypothalamic &unction, which results in abnormal levels o& several hormones ?E$,E1,$,=$D@. Secretion o& gonadotropin=releasing hormone is reduced in patients AB, which reduces levels o& luteini*ing hormone and &ollicle=stimulating hormone 8despite low estrogen levels; ?E$,E1@. 6his prevents ovulation and causes a &unctional hypothalamic amenorrhea. 8See )Oynecologic and reproductive) above.; 2ncreased activation o& the hypothalamic=pituitary=adrenal a5is in AB leads to elevated blood levels o& cortisol 8due to increased production and secretion o& hydrocortisone &rom the adrenal glands, and decreased metabolic clearance; ?$,,1E@. /y contrast, adrenal production o& androgens is diminished with decreased blood levels o& total and &ree testosterone ?1!,1",1$@. 2ncreased cortisol and decreased testosterone may each contribute to osteoporosis. 2n addition,

reduced testosterone leads to a diminished anabolic state and libido. 6here is no therapeutic role &or testosterone replacement therapy ?11@. 8See )+steoporosis) below.; 2n addition, many patients with AB have elevated growth hormone levels and decreased production o& 2OF=2, a pro&ile observed in starvation ?$4=1!,1,,14@. -educed 2OF=2 levels impede bone &ormation ?1!,1,@. 8See )+steoporosis) below.; Antidiuretic hormone levels are also low, which may rarely cause central diabetes insipidus, with &ailure to concentrate urine, and resultant hypernatremia and polyuria. 8See 9Diagnosis o& polyuria and diabetes insipidus9.; Fypothalamic abnormalities in thermoregulation are apparent with hypothermia ?1D@. +ne study &ound hypothermia in percent o& patients with AB ?"0@.

Osteoporosis % At least 0! percent o& &emale patients with AB have osteoporosis, which increases their ris. o& &ractures ?"0,,!,,"@. An epidemiologic study identi&ied !4 patients with AB, and &ound that they were nearly three times more li.ely to su&&er a &racture, compared with the general population ?, @, and an observational study &ound a seven=&old ris. o& &ractures ?,0@. 2n addition, osteoporosis in AB may result in irreversible s.eletal damage and long=term disability such as pain, .yphosis, and short stature ?0,,E,,$@. +steoporosis in AB is characteri*ed by increased bone resorption without concomitant increased bone &ormation ?,$@. 6rabecular bone, &ound in the spine and hips, is a&&ected more than cortical bone ? "@. 6he most severely a&&ected site is the lumbar spine ?,$@. /one loss occurs at a rate o& E to "! percent per year ? "@. Multiple &actors contribute to osteoporosis in AB. <ea. bone mass is generally ac3uired during adolescence and young adulthood, which &re3uently coincides with the onset o& AB ?,$@. 6he pea. bone mass ac3uired by a patient with AB depends upon the time o& onset and duration o& the eating disorder, the degree o& nutritional depletion, and changes in body composition. 6he degree o& osteoporosis in AB is correlated with body loss and duration o& amenorrhea ?0,,1,,,@. 2t is generally accepted that a body mass inde5 o& "$ .gCm and amenorrhea &or 1 months can lead to loss o& bone mineral density ?,$@. A study o& ,0 women with AB 8mean average age ", years; &ound that ! months o& amenorrhea was the threshold above which nearly all patients su&&ered signi&icant bone loss ?,E@. 6he osteoporosis observed in AB di&&ers &rom that &ound in the typical postmenopausal state ?1$@. 2n AB, patients have low serum levels o& estrogen, androgens, 2OF=", and leptin. 2n addition, there are high levels o& cortisol ?1E@ and normal serum levels o& calcium, vitamin D, and parathyroid hormone ?,E@. /one mineral density should be measured with dual=energy S=ray absorptiometry 8DESA; in patients with amenorrhea X si5 months 8&igure ";. For patients who continue to su&&er episodes o& AB, a &ollow=up test should be done every two years ?"!, ",,$@. 6here may be a therapeutic

bene&it in providing patients their DESA results, because visual evidence that patients are at ris. &or &ractures may lead to positive behavioral changes ?,4@. 6he epidemiology and etiology o& osteoporosis in premenopausal women are discussed separately. 8See 9Epidemiology and etiology o& premenopausal osteoporosis9.; Treatment % (eight gain and resumption o& menstrual &unction is the best established treatment &or osteoporosis in patients with AB ?,$,,D=4 @. 6here is limited evidence supporting the use o& hormone therapy in the &orm o& estrogen, recombinant human insulin=li.e growth &actor " 82OF=";, or both. A systematic review identi&ied &ive types o& treatment that have been investigated: weight gain, hormone therapy, bisphosphonates, calcium, and e5ercise ?,$@. -estoration o& weight and menses is the cornerstone o& treatment &or AB, and is associated with improved bone mineral density in patients with AB and osteoporosis ?,$,,D=4",40@. Fowever, it is not clear i& bone loss is &ully reversible. Some studies suggest that normal bone mass is restored &ollowing recovery &rom AB ?4E@, whereas other studies &ound that deminerali*ation was not &ully reversible despite weight gain ?4$@, even a&ter &ollow=up o& one year ?1E@. Supplemental estrogen in the &orm o& oral contraceptive 8estrogen plus progestin; or estrogen replacement therapy has a secondary role in minimi*ing and perhaps reversing osteoporosis in patients with AB ? ",,$@. 6here is limited evidence &rom multiple studies to support this widespread practice ?,!,,$,,D,41@. 6his contrasts with the une3uivocal bene&its seen in postmenopausal osteoporosis. A randomi*ed trial o& "" adolescents with AB &ound that a&ter si5 months, the mean average increase in bone mineral density was signi&icantly higher in patients who received oral contraceptive, compared with patients who received placebo ?4,@. At one year, the mean increase was still higher in patients who received oral contraceptive, but the di&&erence &rom placebo was no longer statistically signi&icant. A randomi*ed trial o& oral contraceptive in E4 women with AB &ound that a&ter appro5imately ".$ years, bone mineral density did not di&&er signi&icantly between patients who received oral contraceptive and patients who received placebo ?4 @. Fowever, in severely ill patients with an initial body weight less than ,! percent o& ideal body weight, patients who received oral contraceptive had a E percent increase in mean average bone density, compared to a ! percent decrease in patients who received placebo. Furthermore, in control patients who started the study weighing less than ,! percent o& ideal body weight and who spontaneously resumed their menses, there was a "D percent increase in bone mineral density. An observational study o& "0! women with AB &ound that use o& estrogen did not predict bone mineral density, but that weight was associated with bone density ?,!@. An observational study o& ,$ women with AB &ound that bone mineral density did not increase in patients receiving oral contraceptives despite a mean average increase in

weight o& " percent. Fowever, weight gain and resumption o& menses were each associated with an increase in bone mineral density ?,D@. Himited evidence suggests that recombinant human insulin=li.e growth &actor " 82OF="; is bene&icial ?44@. A randomi*ed trial assigned 1! women with AB to nine months o& treatment with 2OF=" 80! mcgC.g sc twice daily; alone, 2OF=" plus estrogen and progestin, estrogen and progestin, or placebo. /one mineral density increased signi&icantly in both groups that received 2OF=" compared with placebo ?4D@. 2n addition, the greatest increase occurred in patients who received 2OF=" plus estrogen and progestin. /isphosphonates should not be used routinely in AB ?0,"!@. Hong=term side e&&ects in young patients are un.nown, and bisphosphonates are teratogenic and can persist in the body &or many years a&ter discontinuation o& treatment. /isphosphonates have been used &or severe osteoporosis, especially when AB was unli.ely to remit in the near &uture ?,$@. 6his is based upon the .nown e&&ectiveness o& bisphosphonates in decreasing bone resorption and increasing bone mineral density in osteopenic postmenopausal women and adolescent patients with osteogenesis imper&ecta. Studies o& bisphosphonates include the &ollowing. A one=year randomi*ed trial in 0 adolescents with AB &ound a nonsigni&icant increase in bone mineral density in patients treated with alendronate, compared with placebo ?D!@. An open=label study compared bone mineral density in "! women with AB who received risedronate $ mg per day and "E control patients with AB who did not receive risedronate ?D"@. -isedronate increased bone mineral density by E percent at si5 months and $ percent at nine months. /y contrast, the controls su&&ered bone loss despite weight gain. A &ive percent increase in bone mass over a three year period is generally deemed clinically signi&icant and is associated with a $ percent reduction in &racture ris.. 6he use o& bisphosphonates to treat premenopausal and postmenopausal osteoporosis is discussed separately. 8See 9Evaluation and treatment o& premenopausal osteoporosis9, section on )/isphosphonates) and 9+verview o& the management o& osteoporosis in postmenopausal women9, section on )/isphosphonates).; Attempts to stimulate bone &ormation with anabolic medications such as dehydroepiandrosterone 8DFEA; and transdermal testosterone have &ailed to demonstrate any bene&it &or increasing bone mineral density ?0,,$@. Bo randomi*ed trials have &ound a bene&it &or other anabolic agents such as &luoride, teriparatide, or menatetrenone. 6he use o& androgens &or postmenopausal osteoporosis is discussed separately. 8See 9+verview o& the management o& osteoporosis in postmenopausal women9, section on )Androgens).; Aalcitonin and ralo5i&ene are used to treat postmenopausal osteoporosis and have been studied in premenopausal osteoporosis, but there are no credible studies in AB ?,$@. 8See 9+verview o& the management o& osteoporosis in postmenopausal women9, section on )Aalcitonin) and

9+verview o& the management o& osteoporosis in postmenopausal women9, section on )Selective estrogen receptor modulators) and 9Evaluation and treatment o& premenopausal osteoporosis9 and 9Evaluation and treatment o& premenopausal osteoporosis9, section on )+ther).; Aalcium and vitamin D are not e&&ective in restoring bone mineral content in patients with AB and osteoporosis ?,$@. 2n addition, studies have &ound no correlation between calcium inta.e and bone mineral density in AB, suggesting that ade3uate calcium and vitamin D do not prevent osteoporosis. Fowever, calcium is necessary &or bone maintenance and restoration, and is considered standard treatment &or patients with AB. 6he American Academy o& <ediatrics and the Society &or Adolescent Medicine both recommend that all adolescents ingest between " !! and "$!! mg o& calcium a day with 4!! 2' o& vitamin D to achieve pea. bone mass ?D =DE@. Aalcium and vitamin D supplementation in osteoporosis is discussed separately. 8See 9Aalcium and vitamin D supplementation in osteoporosis9.; A &ew observational studies have &ound that e5ercise e5erts a protective e&&ect upon bone mineral density in patients with AB, consistent with the .nown e&&ect that weight bearing e5ercise has in the general population ?,$,D$@. Fowever, other studies have &ound no relationship between the amount o& physical activity in patients and their bone mineral density. 2n addition, a review o& si5 studies &ound limited evidence supporting the use o& moderate e5ercise to help patients with AB gain weight ?D1@. <atients with osteoporosis should re&rain &rom e5cessive e5ercise and activities that signi&icantly increase the li.elihood o& &ractures ?0@. 6he use o& e5ercise to treat premenopausal and osteoporosis is discussed separately. 8See 9Evaluation and treatment o& premenopausal osteoporosis9, section on )2ntensity o& e5ercise).; 6he evaluation and treatment o& osteoporosis in premenopausal women are discussed separately. 8See 9Evaluation and treatment o& premenopausal osteoporosis9.; Thyroid % Euthyroid hypothyro5inemia may develop in AB, mar.ed by normal to decreased serum levels o& thyro5ine 86E; and triiodothyronine 860; levels, a normal level o& thyroid stimulating hormone 86SF;, and an increased level o& reverse 60 ? "@. 6hyroid tests other than 6SF are not indicated unless there is a strong suspicion o& thyroid dys&unction ?"!@. (hen thyroid abnormalities are suspected, we suggest measuring total 6 E, &ree 60, and 60. 6hyroid hormone replacement is not bene&icial, may be harm&ul, and is thus not indicated ?D,@. 6hyroid &unction in nonthyroidal illness and euthyroid hypothyro5inemia are discussed separately. 8See 96hyroid &unction in nonthyroidal illness9 and 9Euthyroid hyperthyro5inemia and hypothyro5inemia9.; ,ypoglycemia % Dietary restriction accompanied by weight loss and e5cessive e5ercise deplete hepatic glycogen stores and disrupt hepatic gluconeogenesis, resulting in hypoglycemia ? "@. Fypoglycemia rarely causes symptoms in mild cases o& AB. /y contrast, individuals with advanced AB and persistent severe hypoglycemia have a poor prognosis7 severe hypoglycemia has been associated with sudden death due to liver &ailure and a depletion o& substrate to

maintain sa&e blood glucose levels ?D4@. An overview o& hypoglycemia is discussed separately. 8See 9Fypoglycemia in adults: Alinical mani&estations, de&inition, and causes9.; Severe complications can occur in patients with comorbid AB and diabetes ?0@. An overview o& medical care in diabetes mellitus is discussed separately. 8See 9+verview o& medical care in adults with diabetes mellitus9.; *$#TROINTE#TIN$L % Anore5ia nervosa 8AB; consistently causes gastroparesis 8delayed emptying o& the stomach; and constipation ?DD@, and there may be mild elevation o& liver &unction tests ?0@. Acute pancreatitis in patients with AB has been described in case reports ?"!!@. 2n addition, the superior mesenteric artery syndrome is a rare complication o& AB ?"!"@. *astroparesis % Oastroparesis 8delayed gastric emptying; &re3uently develops with &ood restriction and a weight loss o& appro5imately "! to ! pounds 8E.$ to D." .g; ?DD,"! @. 6he main symptom is bloating 8gas and distension;, which o&ten occurs a&ter eating and may be severe. /loating is worsened by a high=&iber diet or by &iber=based la5atives. +ther symptoms o& gastroparesis include early satiety, &ullness, nausea, and vomiting 8not sel&=induced;. Feartburn may also occur as a result o& acidic, vomitus=induced esophagitis &rom &ood remaining in the stomach &or prolonged periods o& time. 2n some cases it may be di&&icult to tell whether vomiting is spontaneous andCor sel&=induced. 6he symptoms o& gastroparesis may inhibit the patient &rom eating and hamper attempts at weight restoration. Oastroparesis in AB should be managed with the &ollowing conservative measures ?", ",0$@: -eassure patients that eating is not causing gastroparesis, which will eventually resolve with weight restoration over &our to si5 wee.s Hi3uid &ood supplements should comprise hal& o& the daily calories &or the &irst wee. or two o& re&eeding 2ngest li3uid components as opposed to solids earlier in the meal Divide the daily calorie inta.e into three small meals and two to three snac.s per day Avoid legume=type &oods, e5cessive &iber, and bran products, which promote gas and distention For patients not responding to these measures, clinicians should use metoclopramide, an oral medication that stimulates stomach contraction and hastens emptying o& the stomach ?"@. A dose o& $ or "! mg, 0! minutes be&ore meals and at bedtime, is use&ul to treat bloating and early satiety secondary to weight loss in AB. 2t also acts as an antiemetic medication. Metoclopramide increases ris. &or tardive dys.inesia with long=term use. Oastroparesis induced by weight loss generally improves with partial weight restoration ?0$,"!0@. A signi&icant improvement o&ten occurs with a "! pound 8E.$ .g; weight gain and the disorder largely resolves with weight gain bac. to 4! percent o& ideal body weight. Fowever, symptoms o& bloating may persist despite weight gain, i& there is ongoing psychopathological distress. 6hus, in

rare cases it may be necessary to obtain a nuclear medicine gastric emptying study to investigate persistent symptoms a&ter re&eeding and weight restoration. Additional in&ormation on gastroparesis is discussed separately. 8See 9Etiology and diagnosis o& delayed gastric emptying9 and 96reatment o& delayed gastric emptying9.; !onstipation % Aonstipation &re3uently accompanies weight loss in AB ?DD@. Symptoms include in&re3uent and small bowel movements and abdominal pain. <atients may incorrectly respond to their constipation or pain by starting treatment with bul.ing, &iber=containing la5atives or stimulant la5atives. 6hese may worsen constipation. 2t is help&ul to reassure patients that bowel patterns in healthy ambulatory patients normally vary &rom two or three times per day to three times per wee., that patients with e5tensive weight loss have even &ewer bowel movements, and that there is nothing &undamentally wrong with their bowels other than a need &or weight gain. (ith weight restoration, the patientTs prior bowel pattern should return over a &ew wee.s. Additional conservative measures to manage constipation in AB include ? ",0$@: (ater 8si5 to eight glasses per day; Fiber in low doses 8"! grams per day; Avoiding high doses o& &iber, which can cause bloating <olyethylene glycol powder 8one to three tablespoons per day;

Hactulose, 0! to 1! mH one to two times per day, should be used as a last resort i& the other measures have &ailed ? ",0$@. Additional in&ormation about the treatment o& constipation is discussed separately. 8See 9Management o& chronic constipation in adults9.; Other % AB can lead to other gastrointestinal complications, including elevated liver &unction tests ?0@, the superior mesenteric artery 8SMA; syndrome ?"!"@, and acute pancreatitis ?"!!@. (eight loss and &asting can mildly elevate liver &unction tests 8aspartate aminotrans&erase, alanine aminotrans&erase, al.aline phosphatase, and bilirubin; ?"!E@. A study o& "E women with AB &ound that alanine aminotrans&erase was elevated in " percent, with a range o& 0" to "1" 'CH 8normal , to 0! 'CH; ?"0@. Hiver wasting may also cause decreased protein synthesis ?""@. -arely, transaminases may be mar.edly elevated with severe AB and a sign o& serious multiorgan &ailure ?"!$@. Butritional rehabilitation is then re3uired ?"4@. An overview o& evaluating patients with elevated liver &unctions tests is discussed separately. 8See 9Approach to the patient with abnormal liver &unction tests9.; 6he superior mesenteric artery 8SMA; syndrome is a rare complication that can occur in AB ?"!,"!"@. 2t results &rom compression o& the third portion o& the duodenum between the aorta posteriorly and the SMA anteriorly. 6he SMA is normally covered with &atty tissue7 weight loss reduces the &at pad and narrows the angle between the two vessels, entrapping the duodenum. Depending upon the severity o& the complication, symptoms include early satiety, abdominal pain soon a&ter starting a meal, nausea, and vomiting. (eight gain o& as little as $ to "! pounds 8 .0 to

E.$ .g; can lead to tolerance o& normal &eeding. 6he clinical mani&estations, diagnosis, and treatment are discussed separately. 8See 9Superior mesenteric artery syndrome9.; Acute pancreatitis in patients with AB has been described in multiple case reports ?"!!@. 6he in&lammation is usually mar.ed by acute upper abdominal pain and elevated serum levels o& pancreatic en*ymes. 6he presumptive etiology is that malnutrition activates proteases, such as trypsin, which damage cells. 2n addition, rapid weight loss may cause retrograde pressure or re&lu5 o& duodenal contents into the pancreatic duct. 6he etiology, clinical mani&estations and treatment o& acute pancreatitis are discussed separately. 8See 9Alinical mani&estations and diagnosis o& acute pancreatitis9 and 96reatment o& acute pancreatitis9 and 9Etiology o& acute pancreatitis9.; REN$L $ND ELE!TROL+TE# % <atients with AB may demonstrate a reduced glomerular &iltration rate and problems concentrating their urine, which leads to diuresis and dehydration ?"!1,"!,@. <atients with restricting AB typically present with low creatinine due to reduced muscle mass ?4@. -enal &unction appears to recover with weight gain. <otassium, magnesium, and phosphate are occasionally depleted ? @, and hypo.alemia may induce nephropathy ?"!4@. Fowever, electrolytes in restricting AB are generally normal, and abnormalities may indicate covert purging. 8See 9Fypo.alemia=induced renal dys&unction9.; -ehydration and repletion o& electrolytes should be corrected prior to re&eeding the patient. Management o& electrolyte abnormalities is discussed separately: 8See 9Maintenance and replacement &luid therapy in adults9, section on )-eplacement &luid therapy).; 8See 9Evaluation o& the patient with hypo.alemia9.; 8See 9Alinical mani&estations and treatment o& hypo.alemia9.; 8See 9Evaluation and treatment o& hypomagnesemia9.; 8See 9Diagnosis and treatment o& hypophosphatemia9.;

( L)ON$R+ % AB can lead to wea.ness and wasting o& respiratory muscles, dyspnea, reduced aerobic capacity, and decreased pulmonary capacity ?"!,"!D@. -espiratory muscle wea.ness and diaphragmatic &unctioning may be slow to recover a&ter re&eeding. An overview o& dyspnea and other causes and diagnosis o& bilateral and unilateral diaphragmatic paralysis are discussed separately. 8See 9Approach to the patient with dyspnea9 and 9-espiratory muscle wea.ness due to neuromuscular disease: Alinical mani&estations and evaluation9.; Several studies have &ound abnormal results o& pulmonary &unction tests in patients with AB ?"!D@. As an e5ample, one study o& , patients with AB and "4 healthy controls demonstrated signi&icant &unctional impairment in patients, which worsened progressively with the duration o& AB ?""!@. 6he nature o& the impairment indicated enlargement o& peripheral lung units without alveolar septa destruction, consistent with changes observed in elderly patients and not in

patients with classic emphysema. 2t is not .nown whether this impairment is reversible with re&eeding. <neumothora5 has been described in case reports, with prolonged air lea. in patients with severe malnutrition ?"""@. 2t is not .nown whether the pulmonary changes that predispose to spontaneous pneumothora5 or persistent air lea. are reversible with re&eeding. <neumothora5 and management o& prolonged air lea. are discussed separately. 8See 9<rimary spontaneous pneumothora5 in adults9, section on )2nitial management) and 9<rimary spontaneous pneumothora5 in adults9, section on )<ersistent air lea.).; <neumomediastinum has also been reported in severe cases o& AB, due to alveolar wall wea.ness and rupture, with conse3uent air lea. into the mediastinum ?"" ,""0@. Symptoms include chest pain, dyspnea, and an5iety, and physical e5amination reveals subcutaneous crepitation. 2n the absence o& traumatic or iatrogenic events, the complication should be managed by radiographic surveillance and resolve within a &ew wee.s without surgical drainage. ,E)$TOLO*I! % Aytopenias and bone marrow changes are observed in AB, and are all reversible with nutritional rehabilitation ?""E="",@. 6he bone marrow is o&ten a&&ected in AB. 2n a study o& EE patients with AB, bone marrow biopsies were classi&ied as normal in "" percent, hypoplastic or aplastic in 0D percent, and gelatinous degeneration with serous &at atrophy in $! percent ?"",@. 6he authors &ound that severity o& bone marrow changes correlated with the degree o& weight loss. <atients with AB may present with anemia, leu.openia, or thrombocytopenia in a pattern involving one, two, or all three cell lines simultaneously ?""E@. Appro5imately 00 percent o& patients with AB are anemic, which tends to be normocytic and normochromic ?""$@. Appro5imately 00 percent o& outpatients with AB and as many as ,$ percent o& inpatients are leu.openic, and both relative lymphopenia and neutropenia have been observed ?"0@. 6hrombocytopenia occurs in $ to "! percent o& patients with AB ?""E@, but there are case reports describing both severe thrombocytopenia and bleeding complications ?""1@. Alinicians should have a lower threshold &or considering in&ectious complications because signs o& in&ection such as &ever may be absent. A retrospective study matched 0 cases o& bacterial in&ection in patients with AB to cases o& bacterial in&ection in patients without AB, and &ound that the diagnosis o& the in&ection was o&ten delayed and that more complications occurred in the patients with AB ?""4@. Fowever, the maGority o& outpatients with AB and leu.openia do not seem to have in&ectious complications, and population=based surveys report that in&ection is not a maGor cause o& death in AB ?""1@. <etechiae and purpura may appear on the e5tremities as a result o& these hematologic complications ? ,""D@.

NE ROLO*I! % /rain atrophy is a complication o& AB that is evident on neuroimaging ?" !," "@. 6he speci&ic clinical implications o& brain atrophy are not .nown. A study &ound that gray matter volume was signi&icantly smaller in adolescents with AB compared with controls, but that per&ormance on neuropsychological tests was comparable e5cept &or one test ?" !@. Speci&ic &indings on magnetic resonance imaging 8M-2; and computeri*ed tomography 8A6; include gray matter 8neuron cell bodies; volume loss and enlarged ventricles. An M-2 study &ound that mean average gray matter volume in 0 women with AB was $ percent less than in " control women, a statistically signi&icant and moderate clinical di&&erence ?" @. 2n addition, an M-2 study o& "1 women with AB and "1 matched healthy women &ound that the right and le&t hippocampus were each signi&icantly reduced by 4 percent in the patients ?" 0@. 2t remains unclear whether these brain changes are related to the loss o& neurons, glia, and neuropil, or are merely due to &luid shi&ts. -esults &rom di&&erent studies suggest that brain atrophy is at least partially reversible with weight restoration ?" "," @. An M-2 study o& women with AB &ound that during short=term @. A second M-2 hospitali*ation and weight restoration to D! percent o& ideal body weight, gray matter volumes increased but remained signi&icantly smaller, compared with control women ?" study o& " &emale adolescents with AB and D controls &ound that gray matter volumes were signi&icantly smaller in the patients at the beginning o& their treatment, but that a&ter seven months, there was no signi&icant di&&erence. DER)$TOLO*I! % 6he cutaneous mani&estations o& AB are numerous. Symptoms o& starvation include, in order o& &re3uency ?"E,""D@: Serosis 8dry, scaly s.in; Hanugo=li.e body hair 8&ine, downy, dar. hair; 6elogen e&&luvium 8hair loss; Aarotenoderma 8yellowing; Acne Fyperpigmentation Seborrheic dermatitis 8erythema and greasy scales; Acrocyanosis 8cold, blue, and occasionally sweaty hands or &eet; <erniosis 8pain&ul or pruritic erythema; <etechiae Hivedo reticularis 8reddish=cyanotic circular patches; <aronychia 8in&lamed lateral and posterior nail &olds; <ruritus Striae distensae 8erythematous or hypopigmented linear patches; Slower wound healing

Serosis on the bac. and arms is &re3uently present due to reduced sebaceous gland secretion ?""D," E," $@. A case series o& 1 patients with AB &ound 5erosis in D, percent ?" 1@. Moisturi*ing ointments and humidi&ying the environment can ameliorate the problem and relieve pruritus. Hanugo hair on the bac., abdomen, and &orearms is not a sign o& virili*ation. Aarotenoderma is due to e5cess ingestion o& carotenoid=rich vegetables that are low in calories, and decreased hepatic catabolism o& carotene. Acne can be caused by starvation, but may also be a ris. &actor &or AB, in that a new dieting behavior intended to control acne may additionally lead to weight loss and then AB. Seborrheic dermatitis 8most commonly on the scalp; should be treated with medicated shampoos. Acrocyanosis is associated with arterial vasoconstriction and secondary dilation o& venules, and may represent a mechanism by which the body conserves heat. Delayed wound healing may be the result o& hypothyroidism and *inc de&iciency. Although most complications improve or resolve with weight gain, striae distensae do not ?" E@. 6opical tretinoin may be used 8but only &or three months; i& the areas are not too large. Sel&=inGurious behavior is common in AB, and patients may show acute or chronic signs o& trauma &rom cuts or burns 8dermatitis arte&acta; ?0,"!," $@. IN"OR)$TION "OR ($TIENT# % 'p6oDate o&&ers two types o& patient education materials, I6he /asicsJ and I/eyond the /asics.J 6he /asics patient education pieces are written in plain language, at the $th to 1th grade reading level, and they answer the &our or &ive .ey 3uestions a patient might have about a given condition. 6hese articles are best &or patients who want a general overview and who pre&er short, easy=to=read materials. /eyond the /asics patient education pieces are longer, more sophisticated, and more detailed. 6hese articles are written at the "!th to "
th

grade reading level and are best &or patients who want in=depth in&ormation and

are com&ortable with some medical Gargon. Fere are the patient education articles that are relevant to this topic. (e encourage you to print or e=mail these topics to your patients. 8You can also locate patient education articles on a variety o& subGects by searching on Ipatient in&oJ and the .eyword8s; o& interest.; /asics topic 8see 9<atient in&ormation: Anore5ia nervosa 86he /asics;9;

# ))$R+ $ND RE!O))END$TION# 6he numerous medical complications o& anore5ia nervosa 8AB; are a direct result o& weight loss and malnutrition. 6he number o& organ systems adversely a&&ected increases with the severity o& weight loss 8table ;. 8See )Oeneral principles) above.; 6reatment &or each complication includes nutritional replenishment, and many complications resolve with weight gain. 6here are &ew randomi*ed trials that have evaluated the management o& medical complications &rom AB. 8See )Oeneral principles) above.;

Aardiovascular complications involve structural abnormalities, including decreased cardiac mass, reduced cardiac chamber volumes, and mitral valve prolapse. 2n addition, &unctional changes include bradycardia, increased L6 dispersion, and hypotension. A prolonged L6 interval may be seen in some patients, but it is not clear whether AB directly causes the syndrome. 8See )Structural changes) above and )Functional changes) above.;

6he reproductive system is altered, causing a cascade o& events resulting in secondary amenorrhea. /y de&inition, all patients with AB have amenorrhea 8&unctional hypothalamic amenorrhea;. Bormal menstrual cycles usually resume with weight gain. Fowever, amenorrhea persists in about "! to 0! percent o& patients with AB despite weight gain. 8See )Oynecologic and reproductive) above.;

<atients may become pregnant despite their amenorrheic state. Fertility is intact in patients who recover &rom AB, and remains stable. Fowever, there is a higher rate o& pregnancy and neonatal complications in AB. 8See )Fertility) above.;

<atients with AB have low levels o& gonadotropin releasing hormone, luteini*ing hormone 8HF;, &ollicle=stimulating hormone 8FSF;, insulin=li.e growth &actor " 82OF=";, &ree testosterone, triiodothyronine 860;, thyro5ine 86E;, leptin, and antidiuretic hormone 8ADF;. 2n addition, there are increased levels o& growth hormone and cortisol. 8See )Endocrine) above.;

+steoporosis occurs in at least 0! percent o& &emale patients with AB, which increases their ris. o& &ractures 8&igure ";. 6he degree o& osteoporosis is correlated with weight loss and duration o& amenorrhea. For patients with AB who are amenorrheic &or more than si5 months, a baseline inde5 o& bone mineral density should be established with dual=energy S=ray absorptiometry 8DESA;. For patients who continue to su&&er episodes o& AB, a &ollow=up test should be done every two years. 8See )+steoporosis) above.;

6he best established treatment &or loss o& bone mineral density in AB is weight gain and resumption o& menses. For patients with AB, amenorrhea, and osteoporosis, it is reasonable to prescribe supplemental calcium and vitamin D. For the most severely ill patients with a body weight less than ,! percent o& ideal body weight, there may possibly be a role &or supplemental estrogen. 8See )6reatment) above.;

Oastroparesis consistently occurs in AB. For patients with AB and gastroparesis, we suggest using li3uid &ood supplements to provide hal& o& the daily calories &or the &irst wee. or two o& re&eeding7 ingesting li3uid components earlier in each meal7 dividing the daily calorie inta.e into three small meals and two snac.s per day7 and avoiding legume= type &oods, e5cessive &iber, and bran products7 rather than metoclopramide to restore bowel &unction 8*rade 3!;. 'nresponsive gastroparesis can be treated with metoclopramide $ or "! mg, 0! minutes be&ore meals and at bedtime. 8See )Oastroparesis) above.;

Aonstipation also occurs o&ten in AB. For patients with AB and constipation, we suggest si5 to eight glasses o& water per day, &iber "! grams per day, and polyethylene glycol

powder one to three tablespoons per day, rather than lactulose to restore bowel &unction 8*rade 3!;. 'nresponsive constipation can be treated with lactulose 0! to 1! mH one to two times per day. 8See )Aonstipation) above.; 'se o& 'p6oDate is subGect to the Subscription and Hicense Agreement. RE"EREN!E# Mehler <S. Diagnosis and care o& patients with anore5ia nervosa in primary care settings. Ann 2ntern Med !!"7 "0E:"!E4. American <sychiatric Association. Diagnostic and Statistical Manual o& Mental Disorders, Fourth Edition, 6e5t -evision, American <sychiatric Association, (ashington, DA, !!!. Eating Disorders: Aore 2nterventions in the 6reatment o& and Management o& Anore5ia Bervosa, /ulimia Bervosa and -elated Eating Disorders. Bational 2nstitute &or Alinical E5cellence, Alinical Ouideline D. http:CCguidance.nice.org.u. 8Accessed on December , !"!;. Sullivan <F. Mortality in anore5ia nervosa. Am J <sychiatry "DD$7 "$ :"!,0. Steinhausen FA. 6he outcome o& anore5ia nervosa in the !th century. Am J <sychiatry !! 7 "$D:" 4E. HPwe /, Qip&el S, /uchhol* A, et al. Hong=term outcome o& anore5ia nervosa in a prospective "=year &ollow=up study. <sychol Med !!"7 0":44". Neel <N, Dorer DJ, Eddy N6, et al. <redictors o& mortality in eating disorders. Arch Oen <sychiatry !!07 1!:",D. Fer*og (, Deter FA, Fiehn (, <et*old E. Medical &indings and predictors o& long=term physical outcome in anore5ia nervosa: a prospective, " =year &ollow=up study. <sychol Med "DD,7 ,: 1D. (orld Fealth +rgani*ation. 6he 2AD="! Alassi&ication o& Mental and /ehavioral Disorders: Alinical Descriptions and Diagnostic Ouidelines. http:CCwww.who.intCclassi&icationsCicdCenCblueboo..pd& 8Accessed on December !,, !"!;. American <sychiatric Association. 6reatment o& patients with eating disorders,third edition. American <sychiatric Association. Am J <sychiatry !!17 "10:E. Fuentebella J, Nerner JA. -e&eeding syndrome. <ediatr Alin Borth Am !!D7 $1:" !". /oateng AA, Sriram N, Meguid MM, Aroo. M. -e&eeding syndrome: treatment considerations based on collective analysis o& literature case reports. Butrition !"!7 1:"$1. Miller NN, Orinspoon SN, Aiampa J, et al. Medical &indings in outpatients with anore5ia nervosa. Arch 2ntern Med !!$7 "1$:$1". Mitchell JE, Arow S. Medical complications o& anore5ia nervosa and bulimia nervosa. Aurr +pin <sychiatry !!17 "D:E04. +livares JH, >Y*3ue* M, Fleta J, et al. Aardiac &indings in adolescents with anore5ia nervosa at diagnosis and a&ter weight restoration. Eur J <ediatr !!$7 "1E:040. Aoo.e -A, Ahambers J/, Singh -, et al. L6 interval in anore5ia nervosa. /r Feart J "DDE7 , :1D. Ooldberg SJ, Aomerci OD, Feldman H. Aardiac output and regional myocardial contraction in anore5ia nervosa. J Adolesc Fealth Aare "D447 D:"$. Mehler <S, (in.elman A/, Andersen DM, Oaudiani JH. Butritional rehabilitation: practical guidelines &or re&eeding the anorectic patient. J Butr Metab !"!7 !"!. Johnson OH, Fumphries HH, Shirley </, et al. Mitral valve prolapse in patients with anore5ia nervosa and bulimia. Arch 2ntern Med "D417 "E1:"$ $. Freed HA, Hevy D, Hevine -A, et al. <revalence and clinical outcome o& mitral=valve prolapse. B Engl J Med "DDD7 0E":". Mehler <S, Nrant* M. Anore5ia nervosa medical issues. J (omens Fealth 8Harchmt; !!07 " :00". 2sner JM, -oberts (A, Feyms&ield S/, Yager J. Anore5ia nervosa and sudden death. Ann 2ntern Med "D4$7 "! :ED. Mehler <S, He*otte D, Ec.el -. Hipid levels in anore5ia nervosa. 2nt J Eat Disord "DD47 E: ",.

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FrPlich J, von Oontard A, Hehm.uhl O, et al. <ericardial e&&usions in anore5ia nervosa. Eur Ahild Adolesc <sychiatry !!"7 "!:$E. Doc5 MN, Oewillig M, Simons A, et al. <ericardial e&&usions in adolescent girls with anore5ia nervosa: clinical course and ris. &actors. Eat Disord !"!7 "4: "4. Melanson EH, Donahoo (6, Nrant* MJ, et al. -esting and ambulatory heart rate variability in chronic anore5ia nervosa. Am J Aardiol !!E7 DE:" ",. Aasiero D, Frishman (F. Aardiovascular complications o& eating disorders. Aardiol -ev !!17 "E: ,. Nanbur B+, Ooldberg E, <inhas H, et al. Second=degree atrioventricular bloc. 8Mobit* 6ype 2; in an adolescent with anore5ia nervosa: intrinsic or ac3uired conduction abnormality. 2nt J Eat Disord !!D7 E :$,$. 'lger Q, OZrses D, +*yure. A-, et al. Follow=up o& cardiac abnormalities in &emale adolescents with anore5ia nervosa a&ter re&eeding. Acta Aardiol !!17 1":E0. (alder A, /aumann <. Aardiac le&t bundle branch bloc. and pancytopenia in anore5ia nervosa: higher ris. with mirta*apine and pantopra*oleK Aase report. <harmacopsychiatry !!D7 E :,D. /ravender 6, Nanter -, Quc.er B. Anore5ia nervosa and second=degree atrioventricular bloc. 86ype 2;. 2nt J Eat Disord !!17 0D:1" . Nrant* MJ, Donahoo (6, Melanson EH, Mehler <S. L6 interval dispersion and resting metabolic rate in chronic anore5ia nervosa. 2nt J Eat Disord !!$7 0,:"11. Mehler <S, Nrant* MJ. L6 dispersion in anore5ia nervosa. Am J Aardiol !!$7 D1:"!0E. Mont H, Aastro J, Ferreros /, et al. -eversibility o& cardiac abnormalities in adolescents with anore5ia nervosa a&ter weight recovery. J Am Acad Ahild Adolesc <sychiatry !!07 E :4!4. Mehler, <S, /irmingham, HA, Arow, SJ, Jahraus, J<. Medical complications o& eating disorders. 2n: 6he 6reatment o& Eating Disorders: A Alinical Fandboo., Orilo, AM, Mitchell, JE 8Eds;, 6he Ouil&ord <ress, Bew Yor. !"!. p.11. -oche F, /arth[l[my JA, Mayaud B, et al. -e&eeding normali*es the L6 rate dependence o& &emale anore5ic patients. Am J Aardiol !!$7 D$: ,,. Facchini M, Sala H, Mal&atto O, et al. How=N\ dependent L6 prolongation and ris. &or ventricular arrhythmia in anore5ia nervosa. 2nt J Aardiol !!17 "!1:",!. Awa*u M, Matsuo.a S, Namima.i 6, et al. Absent circadian variation o& blood pressure in patients with anore5ia nervosa. J <ediatr !!!7 "01:$ E. Oaletta F, Fran*oni F, <rattichi**o F, et al. Feart rate variability and le&t ventricular diastolic &unction in anore5ia nervosa. J Adolesc Fealth !!07 0 :E"1. Derman 6, S*abo A<. (hy do individuals with anore5ia dieK A case o& sudden death. 2nt J Eat Disord !!17 0D: 1!. Nrant* MJ, Mehler <S. -esting tachycardia, a warning sign in anore5ia nervosa: case report. /MA Aardiovasc Disord !!E7 E:"!. Shamim 6, Oolden BF, Arden M, et al. -esolution o& vital sign instability: an obGective measure o& medical stability in anore5ia nervosa. J Adolesc Fealth !!07 0 :,0. Nat* MO, >ollenhoven /. 6he reproductive endocrine conse3uences o& anore5ia nervosa. /J+O !!!7 "!,:,!,. (aller N, Swan SF, (indham OA, et al. 'se o& urine biomar.ers to evaluate menstrual &unction in healthy premenopausal women. Am J Epidemiol "DD47 "E,:"!,". Dou&as AO, Mastora.os O. 6he hypothalamic=pituitary=thyroid a5is and the &emale reproductive system. Ann B Y Acad Sci !!!7 D!!:1$. >yver E, Steinegger A, Nat*man DN. Eating disorders and menstrual dys&unction in adolescents. Ann B Y Acad Sci !!47 ""0$: $0. Dalle Orave -, Aalugi S, Marchesini O. 2s amenorrhea a clinically use&ul criterion &or the diagnosis o& anore5ia nervosaK /ehav -es 6her !!47 E1:" D!. Oolden BF, Aarlson JH. 6he pathophysiology o& amenorrhea in the adolescent. Ann B Y Acad Sci !!47 ""0$:"10. Oolden BF, Jacobson MS, Schebendach J, et al. -esumption o& menses in anore5ia nervosa. Arch <ediatr Adolesc Med "DD,7 "$":"1. Oolden BF, Jacobson MS, Sterling (M, Fert* S. 6reatment goal weight in adolescents with anore5ia nervosa: use o& /M2 percentiles. 2nt J Eat Disord !!47 E":0!".

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Swenne 2. (eight re3uirements &or return o& menstruations in teenage girls with eating disorders, weight loss and secondary amenorrhoea. Acta <aediatr !!E7 D0:"EED. <oyastro <inheiro A, 6hornton HM, <lotonicov NF, et al. <atterns o& menstrual disturbance in eating disorders. 2nt J Eat Disord !!,7 E!:E E. /uli. AM, Fo&&man E-, >on Folle A, et al. 'nplanned pregnancy in women with anore5ia nervosa. +bstet Oynecol !"!7 ""1:""01. Noubaa S, Nouba S, F]llstrPm 6, et al. <regnancy and neonatal outcomes in women with eating disorders. +bstet Oynecol !!$7 "!$: $$. /uli. AM, Sullivan <F, Fear JH, et al. Fertility and reproduction in women with anore5ia nervosa: a controlled study. J Alin <sychiatry "DDD7 1!:"0!. Stewart DE, -obinson E, Ooldbloom DS, (right A. 2n&ertility and eating disorders. Am J +bstet Oynecol "DD!7 "10:""D1. Ho Sauro A, -avaldi A, Aabras <H, et al. Stress, hypothalamic=pituitary=adrenal a5is and eating disorders. Beuropsychobiology !!47 $,:D$. Fa*eli <N, Hawson EA, <rabha.aran -, et al. E&&ects o& recombinant human growth hormone in anore5ia nervosa: a randomi*ed, placebo=controlled study. J Alin Endocrinol Metab !"!7 D$:E44D. Mastora.os O, <avlatou MO, Mi*amtsidi M. 6he hypothalamic=pituitary=adrenal and the hypothalamic= pituitary=gonadal a5es interplay. <ediatr Endocrinol -ev !!17 0 Suppl ":", . Estour /, Oermain B, Diconne E, et al. Formonal pro&ile heterogeneity and short=term physical ris. in restrictive anore5ia nervosa. J Alin Endocrinol Metab !"!7 D$: !0. Miller NN, (e5ler 6H, Qha AM, et al. Androgen de&iciency: association with increased an5iety and depression symptom severity in anore5ia nervosa. J Alin <sychiatry !!,7 14:D$D. Mehler, <S, Ec.el, -, Donahoo, (6. Heptin levels in anore5ia nervosa. 2nt J Eat Disord "DD!7 "$!:4DE. Misra M, Miller NN, Alma*an A, et al. Formonal and body composition predictors o& soluble leptin receptor, leptin, and &ree leptin inde5 in adolescent girls with anore5ia nervosa and controls and relation to insulin sensitivity. J Alin Endocrinol Metab !!E7 4D:0E41. Misra M, Miller NN, Alma*an A, et al. Alterations in cortisol secretory dynamics in adolescent girls with anore5ia nervosa and e&&ects on bone metabolism. J Alin Endocrinol Metab !!E7 4D:ED, . Miller NN, Hawson EA, Mathur >, et al. Androgens in women with anore5ia nervosa and normal=weight women with hypothalamic amenorrhea. J Alin Endocrinol Metab !!,7 D :"00E. Miller NN, Orieco NA, Nlibans.i A. 6estosterone administration in women with anore5ia nervosa. J Alin Endocrinol Metab !!$7 D!:"E 4. Oolden BF, Nreit*er <, Jacobson MS, et al. Disturbances in growth hormone secretion and action in adolescents with anore5ia nervosa. J <ediatr "DDE7 " $:1$$. Orinspoon S, /aum F, Hee N, et al. E&&ects o& short=term recombinant human insulin=li.e growth &actor 2 administration on bone turnover in osteopenic women with anore5ia nervosa. J Alin Endocrinol Metab "DD17 4":041E. D^a* M, /ec.er DE. 6hermoregulation: physiological and clinical considerations during sedation and general anesthesia. Anesth <rog !"!7 $,: $. Orinspoon S, 6homas E, <itts S, et al. <revalence and predictive &actors &or regional osteopenia in women with anore5ia nervosa. Ann 2ntern Med !!!7 "00:,D!. (inston A<, Alwa*eer AE, /an.art MJ. Screening &or osteoporosis in anore5ia nervosa: prevalence and predictors o& reduced bone mineral density. 2nt J Eat Disord !!47 E": 4E. Hucas A-, Melton HJ 0rd, Arowson AS, +)Fallon (M. Hong=term &racture ris. among women with anore5ia nervosa: a population=based cohort study. Mayo Alin <roc "DDD7 ,E:D, . -igotti BA, Beer -M, S.ates SJ, et al. 6he clinical course o& osteoporosis in anore5ia nervosa. A longitudinal study o& cortical bone mass. JAMA "DD"7 1$:""00. Aud^ H, >argas DM, Oussiny[ M, et al. Alinical and biochemical determinants o& bone metabolism and bone mass in adolescent &emale patients with anore5ia nervosa. <ediatr -es !! 7 $":ED,. Mehler <S, MacNen*ie 6D. 6reatment o& osteopenia and osteoporosis in anore5ia nervosa: a systematic review o& the literature. 2nt J Eat Disord !!D7 E :"D$.

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(ong S, Au /, Hau E, et al. +steoporosis in Ahinese patients with anore5ia nervosa. 2nt J Eat Disord !!E7 01:"!E. ,,. /a.er D, -oberts -, 6owell 6. Factors predictive o& bone mineral density in eating= disordered women: a longitudinal study. 2nt J Eat Disord !!!7 ,: D. ,4. Sto&&man B, Schwart* /, Austin S/, et al. 2n&luence o& bone density results on adolescents with anore5ia nervosa. 2nt J Eat Disord !!$7 0,: $!. ,D. Miller NN, Hee EE, Hawson EA, et al. Determinants o& s.eletal loss and recovery in anore5ia nervosa. J Alin Endocrinol Metab !!17 D": D0". 4!. /olton JO, <atel S, Hacey JF, (hite S. A prospective study o& changes in bone turnover and bone density associated with regaining weight in women with anore5ia nervosa. +steoporos 2nt !!$7 "1:"D$$. 4". /ass SH, Sa5on H, Aorral AM, et al. Bear normalisation o& lumbar spine bone density in young women with osteopenia recovered &rom adolescent onset anore5ia nervosa: a longitudinal study. J <ediatr Endocrinol Metab !!$7 "4:4D,. 4 . Nlibans.i A, /iller /M, Schoen&eld DA, et al. 6he e&&ects o& estrogen administration on trabecular bone loss in young women with anore5ia nervosa. J Alin Endocrinol Metab "DD$7 4!:4D4. 40. Oolden BF, Han*.ows.y H, Schebendach J, et al. 6he e&&ect o& estrogen=progestin treatment on bone mineral density in anore5ia nervosa. J <ediatr Adolesc Oynecol !! 7 "$:"0$. 4E. (ent* E, MellstrPm D, Oillberg A, et al. /one density "" years a&ter anore5ia nervosa onset in a controlled study o& 0D cases. 2nt J Eat Disord !!07 0E:0"E. 4$. (ard A, /rown B, 6reasure J. <ersistent osteopenia a&ter recovery &rom anore5ia nervosa. 2nt J Eat Disord "DD,7 :,". 41. -obinson E, /achrach HN, Nat*man DN. 'se o& hormone replacement therapy to reduce the ris. o& osteopenia in adolescent girls with anore5ia nervosa. J Adolesc Fealth !!!7 1:0E0. 4,. Stro.osch O-, Friedman AJ, (u SA, Namin M. E&&ects o& an oral contraceptive 8norgestimateCethinyl estradiol; on bone mineral density in adolescent &emales with anore5ia nervosa: a double=blind, placebo=controlled study. J Adolesc Fealth !!17 0D:4"D. 44. Orinspoon S, Fer*og D, Nlibans.i A. Mechanisms and treatment options &or bone loss in anore5ia nervosa. <sychopharmacol /ull "DD,7 00:0DD. 4D. Orinspoon S, 6homas H, Miller N, et al. E&&ects o& recombinant human 2OF=2 and oral contraceptive administration on bone density in anore5ia nervosa. J Alin Endocrinol Metab !! 7 4,: 440. D!. Oolden BF, 2glesias EA, Jacobson MS, et al. Alendronate &or the treatment o& osteopenia in anore5ia nervosa: a randomi*ed, double=blind, placebo=controlled trial. J Alin Endocrinol Metab !!$7 D!:0",D. D". Miller NN, Orieco NA, Mulder J, et al. E&&ects o& risedronate on bone density in anore5ia nervosa. J Alin Endocrinol Metab !!E7 4D:0D!0. D . Oolden BF, Nat*man DN, Nreipe -E, et al. Eating disorders in adolescents: position paper o& the Society &or Adolescent Medicine. J Adolesc Fealth !!07 00:ED1. D0. /a.er SS, Aochran (J, Flores AA, et al. American Academy o& <ediatrics. Aommittee on Butrition. Aalcium re3uirements o& in&ants, children, and adolescents. <ediatrics "DDD7 "!E:""$ . DE. Folic. MF. >itamin D de&iciency. B Engl J Med !!,7 0$,: 11. D$. Oordon AM, Ooodman E, Emans SJ, et al. <hysiologic regulators o& bone turnover in young women with anore5ia nervosa. J <ediatr !! 7 "E":1E. D1. Qun.er A, Mitchell JE, (onderlich SA. E5ercise interventions &or women with anore5ia nervosa: A review o& the literature. 2nt J Eat Disord !"!. D,. 'tiger -D. Altered thyroid &unction in nonthyroidal illness and surgery. 6o treat or not to treatK B Engl J Med "DD$7 000:"$1 . D4. -ich HM, Aaine M-, Findling J(, Sha.er JH. Fypoglycemic coma in anore5ia nervosa. Aase report and review o& the literature. Arch 2ntern Med "DD!7 "$!:4DE. DD. Qip&el S, Sammet 2, -apps B, et al. Oastrointestinal disturbances in eating disorders: clinical and neurobiological aspects. Auton Beurosci !!17 " D:DD. "!!. Morris HO, Stephenson NE, Ferring S, Marti JH. -ecurrent acute pancreatitis in anore5ia and bulimia. J+< !!E7 $: 0".

"!". Mehler <S, (einer NH. 'se o& total parenteral nutrition in the re&eeding o& selected patients with severe anore5ia nervosa. 2nt J Eat Disord !!,7 E!: 4$. "! . Namal B, Ahami 6, Andersen A, et al. Delayed gastrointestinal transit times in anore5ia nervosa and bulimia nervosa. Oastroenterology "DD"7 "!":"0 !. "!0. /enini H, 6odesco 6, Dalle Orave -, et al. Oastric emptying in patients with restricting and bingeCpurging subtypes o& anore5ia nervosa. Am J Oastroenterol !!E7 DD:"EE4. "!E. Barayanan >, Oaudiani JH, Farris -F, Mehler <S. Hiver &unction test abnormalities in anore5ia nervosa==cause or e&&ect. 2nt J Eat Disord !"!7 E0:0,4. "!$. De Aaprio A, Al&ano A, Senatore 2, et al. Severe acute liver damage in anore5ia nervosa: two case reports. Butrition !!17 :$, . "!1. /oag F, (eera.oon J, Oinsburg J, et al. Diminished creatinine clearance in anore5ia nervosa: reversal with weight gain. J Alin <athol "D4$7 04:1!. "!,. Howinger N, Ori&&iths -A, /eumont <J, et al. Fluid restriction in anore5ia nervosa: a neglected symptom or new phenomenonK 2nt J Eat Disord "DDD7 1:0D . "!4. /rown B(. Medical conse3uences o& eating disorders. South Med J "D4$7 ,4:E!0. "!D. /irmingham AH, 6an A+. -espiratory muscle wea.ness and anore5ia nervosa. 2nt J Eat Disord !!07 00: 0!. ""!. Oardini Oardenghi O, /oni E, 6odisco <, et al. -espiratory &unction in patients with stable anore5ia nervosa. Ahest !!D7 "01:"0$1. """. /i&&l (H, Barayanan >, Oaudiani JH, Mehler <S. 6he management o& pneumothora5 in patients with anore5ia nervosa: A case report and review o& the literature. <atient Sa& Surg !"!7 E:". "" . Filosso <H, Oarabello D, Hyberis <, et al. Spontaneous pneumomediastinum: a rare complication o& anore5ia nervosa. J 6horac Aardiovasc Surg !"!7 "0D:e,D. ""0. Fochlehnert A, HPwe /, /ludau F/, et al. Spontaneous pneumomediastinum in anore5ia nervosa: a case report and review o& the literature on pneumomediastinum and pneumothora5. Eur Eat Disord -ev !"!7 "4:"!,. ""E. FZtter O, Oanepola S, Fo&mann (N. 6he hematology o& anore5ia nervosa. 2nt J Eat Disord !!D7 E : D0. ""$. Misra M, Aggarwal A, Miller NN, et al. E&&ects o& anore5ia nervosa on clinical, hematologic, biochemical, and bone density parameters in community=dwelling adolescent girls. <ediatrics !!E7 ""E:"$,E. ""1. Saito S, Nita N, Morio.a AY, (atanabe A. -apid recovery &rom anore5ia nervosa a&ter a li&e=threatening episode with severe thrombocytopenia: report o& three cases. 2nt J Eat Disord "DDD7 $:""0. "",. Abella E, Feliu E, Oranada 2, et al. /one marrow changes in anore5ia nervosa are correlated with the amount o& weight loss and not with other clinical &indings. Am J Alin <athol !! 7 ""4:$4 . ""4. /rown -F, /artrop -, /eumont <, /irmingham AH. /acterial in&ections in anore5ia nervosa: delayed recognition increases complications. 2nt J Eat Disord !!$7 0,: 1". ""D. Strumia -. S.in signs in anore5ia nervosa. Dermatoendocrinol !!D7 ": 14. " !. Aastro=Fornieles J, /argall_ B, HY*aro H, et al. A cross=sectional and &ollow=up vo5el= based morphometric M-2 study in adolescent anore5ia nervosa. J <sychiatr -es !!D7 E0:00". " ". Ehrlich S, /urghardt -, (eiss D, et al. Olial and neuronal damage mar.ers in patients with anore5ia nervosa. J Beural 6ransm !!47 ""$:D ". " . -oberto AA, Mayer HE, /ric.man AM. /rain tissue volume changes &ollowing weight gain in adults with anore5ia nervosa. 2nt J Eat Disord !"!. " 0. Aonnan F, Murphy F, Aonnor SE, et al. Fippocampal volume and cognitive &unction in anore5ia nervosa. <sychiatry -es !!17 "E1:"",. " E. Strumia -. Dermatologic signs in patients with eating disorders. Am J Alin Dermatol !!$7 1:"1$. " $. 6yler 2, (iseman MA, Araw&ord -2, /irmingham AH. Autaneous mani&estations o& eating disorders. J Autan Med Surg !! 7 1:0E$. 126. Olorio -, Allevato M, De <ablo A, et al. <revalence o& cutaneous mani&estations in !! patients with eating disorders. 2nt J Dermatol !!!7 0D:0E4.

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