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UPDATE ON THE MEDICAL MANAGEMENT OF EATING DISORDERS Dr. Richard L. Levine Professor of Pediatrics and Psychiatry Chief, Division of Adolescent Medicine and Eating Disorders Penn State Hershey Children’s Hospital Case Example  K is a 22 y.o. female college student, track star at a local university.  Asked to leave track team this semester because of malnutrition, referred to student health center for evaluation.  Transferred to HMC for severe malnutrition and medical instability.  Evaluated and admitted to MIMC. Case Example  History of severe restriction of food intake and more than 50 lbs.weight loss over 6-9 months. Seen by Internist during summer and cleared for return to school. Asked to “eat better.”  Significant exercise with running, even the day of admission.  No vomiting or laxative use, but history of diet pill use.  Amenorrhea, and fatigue. Case Example  On examination: Ht. 5’11’’, Wt. 109 lbs.  Vital Signs: pulse 32 bpm, BP 88/56.  Laboratories demonstrated hyponatremia, hypokalemia, hypophosphatemia, abnormal LFT and abnormal renal function tests.  Abnormal EKG with heart block and prolonged QTc.  Abnormal echo with dilated RV, LV, low systolic function, MVP and mitral regurgitation. Case Example  Patient did well in MIMC.  Treated with IV fluids, electrolyte replacement including phosphate replacement.  Nutrition slowly improved. However- found exercising in bed- which was discouraged.  Transferred to medical floor bed and then to inpatient eating disorder facility close to family’s home. Diagnostic Criteria  Established in DSM IV  Useful in setting the diagnostic standard  But should not be applied too strictly in determining who is to be treated, especially in adolescents Diagnostic Criteria  Anorexia Nervosa  Refusal to maintain a normal weight for height, leading to a weight which is less than 85% expected  This may include weight loss or failure to make expected weight gains during a period of growth Diagnostic Criteria  Anorexia Nervosa  An intense fear of gaining weight or becoming fat  A disturbance in the perception of body weight or shape  In post-menarchal females- the presence of secondary amenorrhea for three consecutive menstrual cycles Diagnostic Criteria  Anorexia Nervosa  Two subtypes described: Restricting and Binge eating/Purging  Many adolescents with eating disorders do not fulfill all of these criteria  One should not deny treatment to these “sub-clinical” patients Case 2-Bulimia Nervosa  A.M. was a 16 year old female seen on the GI inpatient service with a history of chronic intractable vomiting. Negative w/u. Symptoms     did not improve after cholocystectomy. Eventually admitted to bulimic symptoms History of sexual activity without contraception Positive testing for chlamydia and herpes History of substance use,depression and cutting behavior Diagnostic Criteria  Bulimia Nervosa  Recurrent episodes of binge eating followed by some recurrent inappropriate compensatory behavior  Binges characterized by eating a very large amount of food over a short period of time and feeling a lack of control over eating Diagnostic Criteria  Bulimia Nervosa  The compensatory behavior can include self- induced vomiting, laxatives, enemas, diuretics or compulsive exercise  This behavior must occur on average twice a week for three months  Also demonstrate over-concern with weight and body shape Diagnostic Criteria  Bulimia Nervosa  Two subtypes described:Purging and Non- purging who use fasting and exercise as the compensatory behavior  Also category of Eating Disorder-Not Otherwise Specified Diagnostic Criteria  Significant controversies regarding the diagnostic criteria and possible modifications for DSM V.  Cutoff weight for AN  Amenorrhea for AN  BED  Role of EDNOS  ED in children Epidemiology  Incidence increased 2-5x in past 30 years  Prevalence of AN is about 1/120 adolescent females  Female to male ratio is 10-1  AN demonstrates a bimodal age range with peaks at 14,18  Bulimia nervosa has     prevalence of 1-5% Increased in older teens Female to male ratio of 5-1 to 20-1 Must consider Dx of AN, BN in males All social, economic, cultural classes Epidemiology  Statistics underestimate prevalence of disturbed body image and eating behavior in teens  50%-67% of adolescent females are dissatisfied with wt, body shape  Majority of female teens have dieted  Many use unhealthy wt control methods such as fasting, diet pills and vomiting  Studies correlate abnormal eating attitudes and behavior with other risk-taking behavior Etiology  Etiology is multifactorial  Biological vulnerability and genetic role  Psychological factors  Cultural influences Etiology  Neuroendocrine dysfunction  Serotonin dysregulation  According to family studies the risk of AN or BN is 7- 20 times more common among a female relative of a patient with an ED than the general population.  Most likely not related, however, to one particular gene or chromosome but rather a “multi- hit” process. Etiology  Psychological factors  Individual problems and family dynamics  Patients with AN demonstrate low self esteem and pervasive sense of ineffectiveness  Depressed, anxious, obsessive, perfectionistic.  BN- problems with impulse control Etiology  Cultural Influences are important  Emphasis on thinness in society  Exacerbated by media  Increase in nutrition and fitness articles  Female body shape of models  Role of excessive exercise  Females in gymnastics and ballet  Males in wrestling Differential Diagnosis  Diagnosis usually selfevident  Must consider other conditions  Eating Disorders can present in patients with another chronic disease       Endocrine Gastroenterlogical Neurological Malignancies Chronic Infection Connective Tissue Diseases  Other Psychological Conditions Evaluation  Screen yearly  Assess with complete H/P  Assess eating behavior, weight history, body image, bingeing/purging, exercise, etc.  Complete PE with vital signs, accurate ht. and wt.  Examine looking for physical sequelae of disease and other diagnoses.  Limited laboratory evaluation. In the office  “Red Flags” on Physical Exam  Bradycardia  Hypotension  BMI  Hypothermia  Parotid enlargement  Enamel Erosion  Acrocyanosis  Russel’s sign- abrasions of knuckles of the hand Medical Complications  Serious medical conditions that require early     and aggressive treatment Affect every organ of the body Some are reversible, but concerns about long-term, irreversible complications 4% mortality associated with anorexia Causes of death include suicide, severe electrolyte disturbances, and arrhythmias Metabolism  Patients with Anorexia have an abnormal metabolism with reduced energy expendituresdemonstrated by indirect calorimetry.  Fat and lean body mass are reduced and extra cellular water volume is expanded.  Physiological adaptation to severe malnutrition.  Concept of “Autocannibalization.” Case - Fluids and Electrolytes  CH is 18 year old female with Anorexia Nervosa with purging features.  Long history of eating disorder behavior with restricting and purging via vomiting.  Presents to the emergency room with syncope.  Ht. 65”, Wt. 76 lbs., BP- 93/65, P-60  Labs included Na 132, CL 84, K 1.4, CO2 36 Fluids and Electrolytes  Patients with Bulimia or Anorexia with purging features can present with significant abnormalities in fluids and electrolytes.  With vomiting this takes the form of a hypokalemic, hypochloremic metabolic alkalosis. Fluids and Electrolytes  Patients with laxative abuse develop metabolic acidosis due to bicarbonate losses in the stool.  Patients with anorexia can present with dehydration if fluid restricting.  Patients can also demonstrate symptomatic hypoglycemia. Case One - GI Complications  J is a 19 year old female presenting with a restricting/bingeing/purging cycle. DiagnosisBulimia Nervosa.  History of depression, self-mutilation treated with medication. History of substance abuse including “huffing”.  History of abdominal pain, hematemesis, involuntary vomiting. Case One -GI Complications  On PE- Ht. 5’4’’, Wt. 139 lbs., epigastic     tenderness Endoscopy revealed esophagitis. Patient treated with PPI, sucralfate, and metoclopramide. Poor compliance with medicationssymptoms persist at the present time. Currently in ED-PHP Case Two-GI Complications  MM is 16 year old female who presented with restricting and weight loss, and amemorrhea. Significant family problems.  On PE- Ht. 5’9’, wt. 94.5 lbs.- emaciated appearance.  Started to eat with treatment but began bingeing. Developed abdominal pain and constipation with laxative abuse. Case Two- GI Complications  Gained a large amount of weight quickly- now up to 150 lbs.  Abdominal pain increased. Saw local GI specialist. Had normal barium enema.  Required colace, lactulose, mineral oil for bowel movements.  Condition has currently stabilized but continues to over eat Gastrointestinal Complications  Depend on the nature of the eating disorder.  With Anorexia Nervosa- complications of decreased gastric and small intestinal motility  Early satiety  Gastroparesis  Chronic constipation Gastrointestinal Complications  With Bulimia Nervosa- complications from the purging behavior.  Can develop chronic constipation from laxative abuse.  Cathartic colon syndrome Gastrointestinal Complications  With Bulimia Nervosa significant complications from chronic vomiting  Complications include involuntary regurgitation from weakening of the gastroesophageal sphincter.  Peptic ulcer disease, gastroesophageal reflux with resulting esophagitis, Mallory-Weiss esophageal tears and even esophageal rupture.  Dental caries and loss of enamel- lingual surfaces Gastrointestinal Complications  Medications options- Proton pump inhibitors, Histamine Blockers  Prokinetic agents such as metoclopramide.  Polyethylene Glycol for chronic constipation. Case OneCardiac Complications  J is a 12 year old female with a history of weight loss for several months.  Ht. 64” and wt. 72 lbs. Her pulse rate was 38 bpm in clinic (18 bpm on the ward) and BP was 74/40 with orthostatic changes.  Her EKG demonstrated borderline QTc abnormality.  Echocardiogram demonstrated a pericardial effusion. Case TwoCardiac Complications  E is a 18 year old female also with at history of significant weight loss and eating disorder symptoms for 2 years.  History of food restriction and purging.  Ht. 65”and Wt. 83 lbs.  Echocardiogram revealed abnormal thinning of anterior and lateral left ventricular walls. Cardiac Complications  Patients with Anorexia demonstrate significant bradycardia and hypotension.  Demonstrate EKG abnormalities and arrhythmias.  Right axis deviations, ST-T wave abnormalities, concerns regarding prolonged QT interval. Cardiac Complications  Changes in myocardial function have been shown including decrease in myocardial tissue mass.  Risk of CHF with too rapid hydration and refeeding. Case ThreeCardiac Complications  KK is a 16 year old female admitted for muscle weakness and dyspnea.  Significant muscle weakness on exam.  QTc abnormality on EKG.  Dilated left ventricle and poor cardiac contractility on echocardiogram Cardiac Complications  Admitted to daily purging with self-induced vomiting via ipecac use for several months.  Significant risk of cardiac damage from abuse of Ipecac. Contains toxic alkaloid- emetine.  Rate of excretion is slow and ingestion of regular doses can accumulate.  Leads to a reversible myopathy.  Significant cardiac toxicity including arrhythmias and cardiomyopathy. Cardiac Complications  Significant risk from OTC diet pill use and abuse.  Most compounds contain stimulantsephedra-like compounds  Herbal stimulants  These drugs can cause cardiac arrhythmias, cardiac ischemia, myocardial infarctions and strokes. Neurological Complications  Alterations in neurotransmitter levels including serotonin and others.  Significant role in the etiology and persistence of the condition.  Associated with psychiatric co-morbidities.  Neuropsychiatric abnormalities include impaired attention, concentration, learning and behavior.Could be associated with resistance seen in treatment Neurological Complications  In severe Anorexia, CT scans have demonstrated cortical atrophy and ventricular dilatation.  These changes have been shown to reversible on CT with refeeding and improved nutrition.  However, abnormalities have been shown to persist on MRI scans even after treatment and weight recovery. Neurological Complications  The most recent study is by Wagner et al in Biological Psychiatry in 2006.  This study looked at MRI scans in 40 recovered patients with AN, AN B/P and BN.  Average length of recovery ranged from 29.8-39.5 months Case One- Endocrine Complications  A is a 24 year old female who presented at age 12 with malnutrition and lack of weight gain. +preoccupation with food and wt and distorted body image.  Ht 59.5” and wt. 76.2 lbs.  Patient diagnosed with AN and treated in outpatient program. She lost more wt. and required 3 inpatient hospitalizations.  Now recovered. Ht. 61” and wt. 120 lbs. Case One- Endocrine Complications  Patient has not reached and will not reach her genetic potential for height.  Patient has had primary amenorrhea and demonstrates osteopenia on DEXA scan.  Patient has had 5 stress fractures associated with running. Endocrine Complications  This case demonstrates several of the potential complications- short stature, amenorrhea, and the risk of osteoporosis. Endocrine Complications  Risk of irreversible short stature in patients that develop AN and malnutrition during their adolescent growth spurt.  A recent study demonstrated that the longer the duration of illness at this time, the more disturbance in growth and increased risk of short stature. Amenorrhea  Primary:  Absence of menses:  By age 16 years with normal pubertal development  By 2 years after completion of sexual maturity  By age 14 without secondary sexual characteristics  Secondary:  Absence of 3-6 consecutive menstrual cycles after menarche Endocrine Complications  Amenorrhea related to dysfunction of the hypothalamic- pituitary- ovarian axis.  Evidence suggests a dysregulation of the hypothalamic secretion of GnRH.  Still under debate if due to primary neuroendocrine dysfunction or secondary to malnutrition with decreased energy availability. Endocrine Complications  Amenorrhea typically occurs when 10-15% of body weight is lost but can occur before significant weight loss.  Resumption of menses (ROM) usually occurs at about 90% of IBW with approximately 20% body fat. Case One- Osteoporosis  JJ is a 25 year old female with a long history of AN and primary amenorrhea.  Medical complications have included hypoglycemic seizures, abnormal renal function tests and osteoporosis.  Bone mineral density on DEXA scan of lumbar spine is 0.598 gm/sq..cm. With a T score of -3.76.  Patient treated with hormonal replacement Osteoporosis: Bone Development  Bone is a living tissue.  It is metabolically active and constantly being turned over and remodeled.  Osteoblasts- Bone forming cells.  Osteoclasts- Bone resorbing cells Osteoporosis- Bone Development  There are three phases to bone mineral development: growth, consolidation and senescence.  Adolescence represents a critical window of opportunity for the development of peak bone mass. Bone Mineral Density  NIH consensus statement—bone mass acquired early in life “most important determinant of lifelong skeletal health”  National Institutes of Health Consensus Statement, 2000  Critical years in bone acquisition between ages 10-14 years  About 90% of peak bone mass is attained by age 18  Bonjour JP, Theinz G, Buchs B, et al. J Bone Mineral Research, 1991 Osteoporosis- Bone Development  There is a linear increase of BMD until early puberty which is accelerated in the perimenarchal years.  The majority of bone mineral accretion occurs by the middle of the second decade. A small fraction is gained in the third decade.  Concept of “bone bank” in relation to calcium and bone mineral metabolism. Bone Density over the lifespan Osteoporosis- Bone Development  Bone mineral acquisition is influenced by nutrition, exercise, and the overall hormonal milieu.  Imbalances in any of these factors can lead to insufficient deposition of calcium in the bone bank and/ or increased loss of calcium from the bone bank.  This can result in osteopenia and osteoporosisdefined by abnormal results on DEXA Scan. Osteoporosis  The majority of women with AN show evidence of bone loss.  At least 50% have evidence of osteoporosis.  This is true even for adolescents with AN.  Two studies have suggested that this is not true for BN. Osteoporosis  The pathogenesis of osteoporosis in patients with AN is not completely known.  Involves both decreased bone formation and increased bone resorption.  Factors include: severe malnutrition, poor calcium intake, excessive exercise, hypoestrogenemia, increased serum cortisol, and other hormonal imbalances. Osteoporosis  There are significant concerns about the     lasting impact and possible irreversibility of the osteoporosis in these young patients. Consider bone density evaluation with a DEXA scan. Currently recommend central DEXA scan T score vs. Z score Other modalities being studied including quantitative CT and ultrasound Osteoporosis  Treat risk with nutritional rehabilitation.  Bone density correlates with BMI.  Addition of calcium of 1500 mg/day with vitamin D.  Lifestyle counseling.  Issue of exercise. Osteoporosis  Controversial issue of medication with hormonal replacement with OCP.  Some studies have demonstrated improvement while others have not.  Important not to make patient complacent about nutrition with OCP.  Other experimental treatments include bisphosphonates, DHEA, IGF-1. Refeeding Syndrome  Nutritional rehabilitation is usually done      orally but sometimes NG feeds are done. HAL seen in literature but ? indication. Initial intake between 800-1500 Kcal/day. Gradual increases of 200-300 Kcal/day. Often takes several days of equilibration before the patient will start to gain weight. Expect inpt.weight gain of 1/4-1/2 lbs./day Refeeding Syndrome  Significant risk of refeeding syndrome in malnourished patients with AN.  Patients are in somewhat of an homeostatic state. Too rapid hydration and/or refeeding can upset this balance.  Risk of edema and CHF.  Often develop abdominal pain and bloating due to decreased gastric emptying. Refeeding Syndrome  Patients are total body phosphate depleted but in relative homeostasis with low normal serum phosphate.  With overly rapid refeeding, (either enteral or parenteral), glucose rapidly enters the cells, followed by phosphate- stimulated by insulin.  This can lead to rapid reduction of serum phosphate.  Thus risk of significant hyophosphatemia if patients receive IV, NG or PO nutrition too rapidly. Refeeding Syndrome  Studies have documented potentially life- threatening arrhythmias as well as mental status changes associated with this hypophosphatemia.  Recent study demonstrated that phosphorus reaches its lowest point during the first week of treatment. Refeeding Syndrome  Monitor weight carefully and serum electrolytes, phosphate frequently.  Prevent/ treat with oral phosphate replacement. IV phosphate replacement if life-threatening. Treatment  Goals of treatment include medical stabilization, nutritional rehabilitation, control of abnormal eating behavior, psychological treatment, and prevention of relapse.  Employ an biopsychosocial model for treatment with a multidisciplinary team.  Treatment options differ sometimes with AN, BN, and EDNOS.  APA Guidelines published as supplement to American Journal of Psychiatry, Jan 2006. Treatment  Medical stabilization and some nutritional rehabilitation must occur before significant psychological progress can be made.  Some psychiatric abnormalities such as depression and food obsession can be starvation induced. Treatment  Indications for hospitalization include: Severe malnutrition- less that 75% Ideal body weight, dehydration and electrolyte disturbances,arrhythmias, other medical complications, acute food refusal, uncontrollable bingeing and purging, acute psychiatric emergency, failure of outpatient treatment Treatment  Inpatient treatment options.  Medical monitoring.  Contracts/Approach.  Discharge criteria.- Study using normalization of vital sign instability as discharge criteria.  Insurance issues. Treatment  Outpatient treatment options.  Multidisciplinary team.  Group therapy.  Individual therapy.  Family therapy  Day treatment programs Treatment  Approximate goal weight of set at 90% of IBW using NCHS tables for teens and “rule of thumb rule” for adults.  Used for medical evaluation and follow- up. Usually do not discuss goal weight with patients. Expect wt. gain of 1-2 lbs./week.  Use goal of resumption of menses.  It is clear that the treatment must be long-term and that there is no quick fix. Treatment- Pharmacotherapy  Many studies indicate that fluoxetine is efficacious in treatment of BN especially in conjunction with therapy.  Usual dose is 60 mg per day.  Studies demonstrate that medication plus therapy more efficacious than either alone.  However, therapy more efficacious than medication alone. Treatment-Anticonvulsants Topiramate  Effective in eliminating binging and purging behavior  Improved self-esteem, eating attitudes, anxiety, and body image  Can see cognitive and peripheral nervous system side effects—slow titration of drug may limit effect Treatment - Pharmacotherapy  Fluoxetine also shown in one study to be helpful in preventing relapse in AN.  No medication clearly shown to help in AN when patient is malnourished.  Other medication options- Olanzapine etc.  Recent trials- Significant reduction in depression, anxiety and core eating disorder disturbances. Significant increase in weight.  Need for more controlled medication trials. Prognosis  Prognosis in adolescents with anorexia is much better than that reported in adult literature.  Studies indicate a 71-86% satisfactory outcome on long-term follow-up  Many of the subjects,however, still did had concerns about weight and eating and one study showed some crossover to bulimic symptoms Prognosis  14-29% of patients had a poor outcome  Factors associated with a poor prognosis included: later onset, longer duration of disease, lower minimum weight, failed previous treatment, greater social and family difficulties, more disturbed personality, increased obsessive somatic concerns, and bulimic subtype Prognosis  Long term prognosis is not as clear with BN, often a history of recovery and relapse.  Study- “Outcome in BN” from AM J Psych     Analysis of 5-10 year outcome studies 50 % patients recovered 20% met full criteria for BN 30% had experienced relapse Conclusion  We live in a culture preoccupied with thinness, reflected in the media  This places an enormous burden on adolescent females in our society  In a vulnerable teen, these pressures can interact with other biological, psychological, and familial factors to lead to an eating disorder Conclusion  Anorexia Nervosa and Bulimia Nervosa are serious illnesses that can have significant, sometimes irreversible medical complications  The prognosis with early recognition and aggressive treatment is very favorable