Dr. Richard L. LevineProfessor of Pediatrics and PsychiatryChief, Division of Adolescent Medicine and Eating DisordersPenn 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 self-evident

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 expenditures- demonstrated 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. Diagnosis- Bulimia 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 medications-

symptoms 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 One- Cardiac 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 Two- Cardiac 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 Three-Cardiac 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 stimulants- ephedra-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 life-long 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 osteoporosis- defined 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-AnticonvulsantsTopiramate 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