are diagnostic criteria for eating disorders markers of medical severity?

DOI: 10.1542/peds.2008-1777 2010;125;e1193-e1201; originally published online Apr 12, 2010; Pediatrics

Rebecka Peebles, Kristina K. Hardy, Jenny L. Wilson and James D. Lock Are Diagnostic Criteria for Eating Disorders Markers of Medical Severity?

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Are Diagnostic Criteria for Eating Disorders Markersof Medical Severity?

WHAT’S KNOWN ON THIS SUBJECT: Few studies have focused onany medical sequelae in adolescents with eating disorders nototherwise specified.

WHAT THIS STUDY ADDS: This study provides evidence thatserious medical complications can occur in children andadolescents with eating disorders who do not meet full DSM-IVcriteria for anorexia nervosa or bulimia nervosa.

abstractOBJECTIVE: The objective of this study was to compare the medicalseverity of adolescents who had eating disorders not otherwise spec-ified (EDNOS) with those who had anorexia nervosa (AN) and bulimianervosa (BN).

METHODS: Medical records of 1310 females aged 8 through 19 yearsand treated for AN, BN, or EDNOS were retrospectively reviewed. Pa-tients with EDNOS were subcategorized into partial AN (pAN) and par-tial BN (pBN) when they met all Diagnostic and Statistical Manual ofMental Disorders, Fourth Edition criteria but 1 for AN or BN, respec-tively. Primary outcome variables were heart rate, systolic blood pres-sure, temperature, and QTc interval on electrocardiogram. Additionalphysiologically significant medical complications were also reviewed.

RESULTS: A total of 25.2% of females had AN, 12.4% had BN, and 62.4%had EDNOS. The medical severity of patients with EDNOS was interme-diate to that of patients with AN and BN in all primary outcomes. Pa-tients with pAN had significantly higher heart rates, systolic bloodpressures, and temperatures than those with AN; patients with pBN didnot differ significantly from those with BN in any primary outcomevariable; however, patients with pAN and pBN differed significantlyfrom each other in all outcome variables. Patients with pBN and BN hadlonger QTc intervals and higher rates of additional medical complica-tions reported at presentation than other groups.

CONCLUSIONS: EDNOS is a medically heterogeneous category with se-rious physiologic sequelae in children and adolescents. Broadening ANand BN criteria in pediatric patients to include pAN and pBN may proveto be clinically useful. Pediatrics 2010;125:e1193–e1201

AUTHORS: Rebecka Peebles, MD,a Kristina K. Hardy, PhD,b

Jenny L. Wilson, BA,a and James D. Lock, MD, PhDc

aDivision of Adolescent Medicine, Department of Pediatrics,Stanford University School of Medicine, Mountain View,California; bDepartment of Psychiatry and Behavioral Sciences,Duke University Medical Center, Durham, North Carolina; andcDivision of Child and Adolescent Psychiatry, Department ofPsychiatry and Behavioral Sciences, Stanford University Schoolof Medicine, Stanford, California

KEY WORDSchildren and adolescents, adolescent medicine, eatingdisorders, child psychiatry

ABBREVIATIONSEDNOS—eating disorders not otherwise specifiedDSM-IV—Diagnostic and Statistical Manual of Mental Disorders,Fourth EditionBN—bulimia nervosaAN—anorexia nervosapAN—partial anorexia nervosapBN—partial bulimia nervosaED—eating disorderMBW—median body weightBP—blood pressurepBN-binge/purge—partial bulimia nervosa that does not meetbinging and purging frequency criteriapBN-binge only—partial bulimia nervosa, binging but notpurgingpBN-purge only—partial bulimia nervosa, purging but notbingingpAN-low weight/menstruating—partial anorexia nervosa thatdoes not meet menstrual criteriapAN-low weight/not menstruating—partial anorexia nervosathat meets weight and menstrual criteriapAN-�90%—partial anorexia nervosa, 85% to 90% of medianbody weightpAN-25%—partial anorexia nervosa, lost�25% of premorbidweight at presentationSMR—sexual maturity rating

www.pediatrics.org/cgi/doi/10.1542/peds.2008-1777

doi:10.1542/peds.2008-1777

Accepted for publication Jan 7, 2010

Address correspondence to Rebecka Peebles, MD, StanfordUniversity School of Medicine, Division of Adolescent Medicine,1174 Castro St, Suite 250A, Mountain View, CA 94040. E-mail:[email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2010 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose.

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According to current diagnostic crite-ria, most pediatric patients with disor-dered eating receive a diagnosis ofeating disorders not otherwise speci-fied (EDNOS), defined in the Diagnosticand Statistical Manual ofMental Disor-ders, Fourth Edition (DSM-IV) as “disor-ders of eating that do not meet the cri-teria for any specific eating disorder,”1

a categorization that has long troubledpractitioners.2–9 Although a handful ofstudies have examined bone density,fracture rates, or electrocardiogramsof patients with EDNOS,10–12 most stud-ies on medical sequelae of disorderedeating have focused on bulimia ner-vosa (BN) or anorexia nervosa (AN),and little work has documented the se-verity, frequency, or clinical signifi-cance of EDNOS in young people.4,8,13–15

Studies of patients with EDNOS have fo-cused on psychiatric features, com-paring adult patients who had partialAN (pAN) or partial BN (pBN) with pa-tients who met full DSM-IV criteria. Pa-tients with pAN and pBN typically havesimilar psychological profiles to thosewho meet full criteria for AN and BN,whereas pAN and pBN differ signifi-cantly from each other despite thatboth are subgroups of EDNOS.4,16–30

Numerous medical organizations, in-cluding the American Academy of Pedi-atrics, agree that patients with eatingdisorders and severe malnutrition,bradycardia, hypotension, hypother-mia, or orthostasis are critically ill andrequire hospitalization.31,32 No studyhasexaminedhowDSM-IVdiagnostic cri-teria correlate with medical severity,and there are no data to validate thecommonly held tenet that EDNOS is asso-ciated with lower medical severity.

This article reviews current diagnosticcriteria and discusses their utility inpredicting the medical severity of pa-tients with eating disorders (EDs). Ourgoal is to describe a large group of pe-diatric patients with EDNOS and com-pare them with pediatric patients with

AN and BN. In addition, we compare themedical severity of adolescents whohave EDNOSwith pAN or pBNwith thosewho meet full diagnostic criteria. Wepredicted that those with EDNOS andpAN or pBN would be less medicallycompromised than those with fullDSM-IV syndromes. Furthermore, wepredicted that pAN and pBN would dif-fer significantly from one other withrespect to meeting hospitalizationcriteria.

METHODS

Patients

All 1310 female patients who wereaged 8 to 19 years and had been diag-nosed with AN, BN, or EDNOS in an aca-demic pediatric ED program from Jan-uary 1997 through April 2008 wereidentified. All patients initially receiveda clinical diagnosis from a board-certified psychiatrist or psychologistwith expertise in the assessment ofchildren and adolescents with ED, af-ter diagnostic interviews with both pa-tients and parents or guardians, andas part of a comprehensive evaluationby a multidisciplinary team. Both inpa-tients and outpatients were included.

Because of small within-gender cellsizes that prevented adequate assess-ment of potential gender differences,male patients were excluded fromanalyses, as were patients who werefound not to have a DSM-IV–diagnos-able ED during their evaluation ortreatment. A waiver of informed con-sent and a Health Insurance Portabilityand Accountability Act–compliantwaiver of individual authorizationwere granted; all data collection proto-cols were approved by our Panel onMedical Research in Human Subjectsand compliant with the Health Insur-ance Portability and Accountability Actof 1996.

DSM-IV criteria for EDs are guidelinesand allow for latitude in their applica-tion in clinical settings; however, thisstudy was designed to answer a pri-mary research question of how DSM-IVdiagnostic criteria predict medicaloutcomes. A systematic retrospectivereview of all medical records was con-ducted, therefore, by 2 independent as-sessors and reviewed by the primaryinvestigator to note relevant clinicalparameters at presentation. When in-dicated after this comprehensive re-

FIGURE 1Diagnostic categorizations for analyses.

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view, patients were recategorizedfrom their original clinical ED diagno-sis, by using strict DSM-IV criteria (Fig1). In premenarchal females, AN wasdiagnosed when weight and psychiat-ric criteria were met as per DSM-IVguidelines.

Variables and Outcomes

Predictor variables for primary analy-ses were categorical diagnoses ofEDNOS, AN, and BN. To examine eachseparate criterion for AN and BN in theDSM-IV,1 we further categorized pa-tients with EDNOS into nonoverlappingpAN and pBN categories:

1. pBN-binge/purge: patients whobinge-ate and purged (defined byself-induced vomiting only or laxativeabuse) in themonth before presenta-tion but with less frequency than de-fined in the DSM-IV;

2. pBN-binge only: patients who binge-ate with no purging behaviors, sim-ilar to binge-eating disorder butwith any level of frequency of bingeeating;

3. pBN-purge only: patients who purgedwith no binge-eating behaviors;

4. pAN-low weight/menstruating: pa-tients who met weight criteria forAN but not menstrual criteria;

5. pAN-low weight/not menstruating:patients who met menstrual andweight criteria for AN but did notopenly acknowledge psychiatriccriteria, although exhibiting denialof the severity of their underweightalong with weight and shape con-cerns by parental report were suf-ficient to diagnose a clinical eatingdisorder;

6. pAN-�90%: patients who met men-strual criteria for AN and weighed�85% median body weight (MBW)but�90%; or

7. pAN-25%: patients who were not inother categories of pAN or pBN buthad lost�25% of premorbid weight

at presentation; the DSM-III sug-gested that patients with this de-gree of weight loss be eligible forthe diagnosis of AN even if theywere not �85% MBW,33 althoughthis convention was dropped forthe DSM-IV.

Medical outcome variables are definedin Table 1 on the basis of nationalguidelines for acute hospitalization ofadolescentswith EDs.2,32,34 Primary out-comes were heart rate, blood pres-sure (BP), temperature, and QTc inter-val. Severe malnutrition was not aprimary outcome in this study becausepAN and pBN categories were partlydefined by weight. Secondary outcome

variables included rates of admissionwithin 2 weeks of presentation, lengthof disease, complications that were at-tributed to the ED before presentation,and complications that occurred dur-ing the first hospital stay if the hospi-talization occurred within 2 weeks ofpresentation. There were no deaths inthis series during the first hospitalstay.

Heart rates (measured manually) andBPs (using a sphygmomanometer)were taken after lying supine for 5min-utes, and standing heart rate and BPwere taken after standing for 2 min-utes. When heart rates or BPswere lowsupine or when significant dizziness

TABLE 1 Medical Outcome Variables

Variable Description

Bradycardiaa �50 beats per minuteHypotensiona Systolic BP�90 mm HgOrthostatic by heart rate �20-beat rise in heart rate from lying

to standingOrthostatic by BP �10-point drop in systolic BP from lying

to standingHypothermiaa Oral temperature�35.6°CQTc prolongationa QTc interval�440 msHypokalemia Serum potassium�3.2Hypophosphatemia Serum phosphorus�3.0Severe malnutrition Percentage MBW�75Serious complications before first visit (obtained from Arrhythmiasthe medical record as a report from patient, Ascitesparent, or outside health care professional) Edema

HematemesisHypokalemiaHypophosphatemiaPancreatitisPericardial effusionPneumothorax/pneumomediastinumRenal calculiSeizureSuperior mesenteric artery syndromeSyncope

Serious hospital complications (noted by medical Hematemesisteam during hospital stay and recorded in the Hypokalemia (potassium�3.0)medical record) Hypophosphatemia (phosphorus�3.0)

PancreatitisPericardial effusionQTc prolongation�450 msRefeeding syndromeSeizureSerious arrhythmiasSuperior mesenteric artery syndromeSyncopeTransfer to the ICUVasopressor requirement

a Primary outcomes were continuous: heart rate, BP, temperature, and QTc interval.

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was reported, standing vital signswere not obtained. Temperatureswere obtained orally by using a digi-tal thermometer. Electrocardiogramswere performed by trained staff mem-bers by using a standard 12-leadmethod. Weights were recorded ingowns with no clothing, and heightswere obtained by using a stadiometer.Because electrocardiograms and lab-oratory values were performed clini-cally rather than as part of a researchprotocol, the majority of but not all pa-tients had these tests performed(Table 2).

Percentage Median Body Weight

BMI was calculated by using the equa-tion BMI�weight in kg/(height in m)2.MBW was calculated by using gender-specific 2000 Centers for DiseaseControl and Prevention BMI-for-agegrowth charts for children and ad-olescents aged 2 to 20 years (www.cdc.gov/growthcharts). The 50th per-centile BMI for exact age at presenta-tion on the Centers for Disease Controland Prevention chart was used to cal-culate an MBW, together with theheight at presentation.

Rate of Weight Loss

Reported maximum weights were ex-tracted from the medical record. Totalweight loss before presentation wasdefined as the maximum weight minusthe weight at presentation. Total per-centage weight loss was defined as thetotal weight loss divided by the maxi-mum weight, multiplied by 100. Therate of weight loss was defined as totalpercentage weight loss divided by themonths from the date of maximumweight to the date of presentation. Whenthe maximum weight was the weight atpresentation, the totalweight losswas 0,as was the rate of weight loss.

Statistical Analysis

Data were described with standardmean and frequency statistics and an-

TABLE 2 Demographic and Clinical Description: Overall Data Set

Parameter n % Mean SD

Age, y 1310 15.4 2.0Ethnicity 1273White 959 75.3Asian 105 8.2Hispanic 96 7.5Black 14 1.1Pacific Islander 3 0.2Other 96 7.5Diagnosis 1310AN 330 25.2BN 162 12.4EDNOS 811 62.4pAN 408 31.1pAN-low weight/menstruating 111 8.5pAN-low weight/not menstruating 130 9.9pAN-�90% MBW 121 9.2pAN-25% 46 3.5pBN 223 17.0pBN-binge/purge 79 6.0pBN-purge only 86 6.6pBN-binge only 58 4.4

SMR: breasts 10201 54 5.32 51 5.03 120 11.84 332 32.55 463 45.4Hormonal contraception 109 8.3Months of disease 1300 15.3 14.4Percentage of MBW 1310 89.7 18.0Severe malnutrition 218 16.6Percentage weight loss 1239 17.9 10.7Rate weight loss, %/mo 1176 2.2 2.1Heart rate, bpm 1310 61 15Bradycardia 333 25.4Systolic BP, mm Hg 1308 106 11Hypotension 81 6.2Temperature, °C 1298 36.7 0.5Hypothermia 46 3.5Change in heart rate 1104 18 12Orthostatic by heart rate 415 37.6Change in systolic BP 1104 3 9Orthostatic by BP 62 5.6QTc interval, ms 1088 392 28QTc prolongation 41 3.8Potassium, mmol/L 1179 4.0 0.4Hypokalemia 26 2.2Phosphorus, mg/dL 1074 3.9 0.6Hypophosphatemia 54 5.0Met medical admission criteriaAny 848 64.7Any except weight 790 60.3

Status at initial evaluation/presentationOutpatient 685 52.3Inpatient 624 47.7Admitted to hospital or admission recommended

within 2 wk of first presentation894 68.3

Length of stay if admitted, d 890 17.3 11.7Serious hospital complications if hospitalized

within 2 wk of presentation169 19.0

Serious complications reported beforepresentation

266 20.2



alyzed by using �2 testing, Student’s ttesting, and analysis of variance withTukey’s posthoc comparisons testingon SPSS 17.0 software (SPSS, Inc, Chi-cago, IL). To guard against type I errorin analysis of the primary aims, weused a Hochberg modified Bonferroniprocedure.35 To assess further the re-lationships between primary predictorand outcome variables, we added ageand length of disease as covariates byusing analysis of covariance.

RESULTS

Demographic and clinical characteris-tics are presented in Table 2. Table 3outlines medical differences betweenDSM-IV ED categories at presentation.The medical severity of patients withEDNOS fell between that of patientswith AN and BN in most criteria exam-

ined. Differences were statistically sig-nificant for all primary outcomes. Pe-diatric patients with EDNOS hadsimilar age, length of disease, and rateof weight loss as those with AN, but,otherwise, posthoc testing revealedthat most differences in secondaryoutcomes were significant among all 3diagnostic categories.

Medical outcomes were compared be-tween patients with pAN and AN, pBNand BN, and pAN and pBN (Table 4). Pa-tients with pAN did not differ fromthose with AN in sexual maturity rating(SMR), but patients with pBN wereslightly less pubertally mature thantheir BN counterparts (SMR breast: 4.5vs 4.7 [t� 2.6, P� .05]; pubic hair: 4.5vs 4.7 [t� 2.8, P� .01]). All differencesthat were noted in primary analyses

and detailed in Tables 3 and 4 retainedsignificance after the Hochberg modi-fied Bonferroni correction was ap-plied, except for those related to tem-perature differences between patientswith pBN and BN. Of note, all relation-ships between primary predictor andoutcome variables remained signifi-cant after controlling for age andmonths of disease.

In exploratory analyses, pAN sub-groups were compared with AN, andpBN subgroups were compared withBN. Patients with pAN-low weight/men-struating were significantly older,whereas those who did not meet psy-chiatric criteria were the youngest(15.8 vs 14.3 years: pAN-low weight/notmenstruating; 14.8: pAN-�90%; 15.0:pAN-25%; and 15.3: AN [F � 9.7, P �.001]). Patients with pAN-low weight/not menstruating had the longest QTcintervals (394 vs 393: pAN-low weight/menstruating; 386: pAN-�90%; 378:pAN-25% [F � 3.0, P � .05]). The pAN-25% group, despite being nearly attheir MBW (97.7% vs 77.7%: pAN-lowweight/menstruating; 75.7%: pAN-lowweight/not menstruating; 87.2%: pAN-�90%; and 75.8%: AN [F � 198.8, P �.001]), demonstrated the highest per-centage of weight lost (34.0% vs 19.6%,16.6%, 19.2%, and 23.0% [F� 32.9, P�.001]) at the fastest rate (3.5% vs 2.6%,2.8%, 2.4%, and 2.4%/mo [F� 3.9, P�

.005]). They also had higher rates ofbradycardia (43.5% vs 22.5%, 28.5%,28.9%, and 38.5% [�2� 14.4, P� .01])and orthostasis by heart rate (57.1%vs 52.7%, 37.0%, 32.4%, and 32.8%[�2 � 18.0, P � .001]) than all otherpAN subgroups and were more likelythan all except patients with AN tomeet any admission criteria, excludingweight (76.1% vs 66.7%, 61.5%, 59.5%,and 73.0% [�2 � 11.8, P � .05]). Pa-tients with AN were most likely to havehypotension (16.2% vs 2.7%: pAN-lowweight/menstruating; 6.9: pAN-lowweight/not menstruating; 5.0: pAN-

TABLE 3 Comparison of EDNOS With AN and BN

Parameter AN EDNOS BN �2 F

Age 15.3 15.2 16.4 26.6a,b

Months of disease 14.0 13.7 26.6 61.7a,b

% MBW, mean 75.8 92.0 106.6 242.6a,c

% Severe malnutrition 38.2 11.2 0.0 159.9a

% Weight loss, mean 23.0 16.6 13.2 62.2a,c

Rate loss, mean, %/mo 2.4 2.3 1.4 12.9a,b

Heart rate, mean 56 63 66 31.9a,c

% Bradycardia 38.5 23.3 9.3 53.9a

Systolic BP, mean 101 107 111 68.7a,c

% Hypotension 16.4 2.9 1.9 79.3a

Temperature, mean 36.6 36.7 36.9 21.6a,c

% Hypothermia 5.8 3.3 0.0 10.8d

Change in heart rate, mean 18 19 17 1.8% Orthostatic by heart rate 32.8 40.1 33.3 5.5e

Change in BP, mean 2 3 3 2.1% Orthostatic by BP 6.7 5.6 3.9 1.4QTc interval, mean 388 393 401 10.3a,c

% QTc prolongation 4.2 3.2 6.0 2.5Serum potassium, mean 3.9 4.0 3.9 0.3% Hypokalemia 2.2 1.7 4.8 5.6e

Serum phosphorus, mean 3.8 4.0 4.0 14.6a,f

% Hypophosphatemia 8.3 3.8 3.3 9.4d

% Met admission criteriaAny 81.8 61.6 45.7 71.4a

Any except weight 73.0 58.1 45.7 38.5a

Length of stay, mean, d 20.3 16.3 11.5 20.0a,c

% Serious hospital complications 23.2 16.5 20.3 5.7e

% Serious previous complications 16.4 19.7 31.5 15.9a

a P� .001.b Significant differences on posthoc testing between AN and BN and between EDNOS and BN.c Significant differences among all 3 groups on posthoc testing.d P� .01.e P� .1.f Significant differences between AN and BN and between AN and EDNOS.

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�90%; and 6.5: pAN-25% [�2 � 26.6,P � .001]) and had the lowest phos-phorus levels (3.7 vs 3.9, 4.0, 3.9, and3.8 [F � 3.7, P � .005]). There wereno differences noted among pAN sub-groups and AN with regard to ratesof hypothermia, orthostatic hypoten-sion, hypokalemia, serious hospitalcomplications, or complications be-fore presentation.

Most pBN subgroups did not show sig-nificant differences from each other inmedical hospitalization criteria, al-though small cell sizes precludedmeaningful analyses of some categor-ical outcomes. Patients with BN wereolder (16.4 vs 15.8 years: pBN-binge/purge; 15.6: pBN-purge only; and 15.6:pBN-binge only [F � 6.4, P � .001])and had disease longer than all pBNsubgroups (26.6 mo vs 19.4, 16.5, and

18.7 months [F � 8.5, P � .001]). Pa-tients with pBN-purge only had lostweight faster than patients with BN(2.4% vs 1.5%/month: pBN-binge/purge; 1.9%/month: pBN-binge only;and 1.4%/month: BN [F � 3.0, P �.05]). There were no differences be-tween groups in mean percentageweight loss, BP, orthostatic changes,potassium and phosphorus levels,length of stay if hospitalized, andcomplication rates.

DISCUSSION

These analyses reveal that in this ado-lescent population with ED, 62.4% re-ceived a proper diagnosis of EDNOSwhen current DSM-IV standards werestrictly applied; however, 61.6% ofthese patients with EDNOS met recom-mended criteria for medical hospital-

ization and were more compromisedthan patients with BN in most medicaloutcomes. Despite their younger age,they displayed similar disease dura-tion and rates of weight loss, QTcprolongation, orthostasis, and hypo-kalemia as their full diagnostic coun-terparts. This is despite that theyweighed significantly more than pa-tients with AN. These results do notsupport our initial hypothesis thatEDNOS would be less medically severethan AN or BN.

We proposed new groupings of pa-tients with pAN and pBN within theEDNOS group, with each subgroup di-rectly challenging 1 DSM-IV criterionfor AN or BN. When patients with pANwere compared with those with AN,there were few differences. Patientswith pAN as a whole were less likely tohave a low heart rate or BP but did notdiffer from patients with AN on mostother medical outcomes. Adolescentswith pAN were younger and weighedsignificantly more but had lost weightmore rapidly than those with AN andhad a shorter disease duration.

Of pAN subgroups, patients who hadEDNOS and had lost �25% of theirpremorbid body weight (pAN-25%)seemed more compromised thanother subgroups of pAN and evenmorethan patients with AN in some medicaloutcomes. This is the case despite be-ing at a significantly higher, near“ideal” body weight, reminding us thatmalnutrition is a complex disease withmanifestations at multiple weights. Inaddition, those with pAN-low weight/menstruating were older, possibly in-dicating later recognition of the ED. Pa-tients with pBN were younger, had ashorter duration of disease, weighedless, and had lost weight more rapidlythan their BN counterparts; however,patients with pBN and subgroups didnot differ significantly from adoles-cents with BN on most other medicaloutcomes examined.

TABLE 4 Comparisons of Medical Data Among Diagnostic Subgroups

Parameter pAN AN �2/t pBN BN �2/t pAN vs pBN

Age 15.0 15.3 2.3a 15.7 16.4 4.1b �4.5b

Months of disease 12.0 14.0 2.2a 18.1 26.6 4.9b �5.5b

% MBW, mean 82.2 75.8 �10.6b 104.7 106.6 1.1 �19.5b

% Weight loss, mean 20.2 23.0 3.6b 12.8 13.2 0.3 8.3b

Rate loss, mean, %/mo 2.7 2.4 �2.1a 1.9 1.4 �2.2a 3.9b

Heart rate, mean 61 56 �4.3b 66 66 0.6 �3.1c

% Bradycardia 28.7 38.5 7.9c 12.1 9.3 0.8 22.5b

Systolic BP, mean 105 101 �5.0b 111 111 �0.04 �8.1b

% Hypotension 5.1 16.4 25.3b 1.3 1.9 0.2 5.7a

Temperature, mean 36.7 36.6 �2.4a 36.8 36.9 2.1d �2.9c

% Hypothermia 5.2 5.8 0.2 0.9 0.0 1.4 7.4c

Change in heart rate, mean 19 18 �1.6 19 17 �1.1 0.4% Orthostatic by heart rate 42.0 32.8 5.0a 38.2 33.3 0.9 0.8Change in BP, mean 3 2 �1.3 4 3 �0.5 �1.0% Orthostatic by BP 6.8 6.7 0.0 4.8 3.9 0.2 0.9QTc interval, mean 390 388 �0.8 399 401 0.7 �3.7b

% QTc prolongation 2.5 4.2 1.6 4.8 6.0 0.2 1.9Serum potassium, mean 4.0 3.9 �0.4 4.0 4.0 �0.4 �0.3% Hypokalemia 1.3 2.2 0.8 3.2 4.8 0.4 2.2Serum phosphorus, mean 3.9 3.8 �3.6b 4.0 4.0 0.3 �0.9% Hypophosphatemia 5.2 8.3 2.4 3.0 3.3 0.2 1.3% Severe malnutrition 22.5 38.2 21.4b 0.0 0.0 NA NA% Met admission criteriaAny 71.1 81.8 11.5b 47.5 45.7 0.1 34.2b

Any except weight 64.0 73.0 6.9c 47.5 45.7 0.1 16.0b

Length of stay, mean, d 17.8 20.3 2.6a 13.8 11.5 �1.5 3.1c

% Serious hospital complications 18.2 23.2 2.4 19.0 20.3 0.04 0.04% Serious previouscomplications

18.1 16.4 0.4 25.1 31.5 1.9 4.3a

NA indicates not applicable.a P� .05.b P� .001.c P� .01.d Did not retain significance when Hochberg modified Bonferroni correction was applied.



When pAN was compared with pBN, pa-tients with pAN had a more medicallysevere condition, with the exception ofduration of illness and the QTc interval:patients with pBN had more months ofdisease and longer QTc intervals. Thismirrors our comparison of BN with AN:patients with BN report nearly twicethe duration of disease and longermean QTc intervals. Patients with pANand pBN were similar only in rates ofhypokalemia, hypophosphatemia, andorthostasis. This lends credence to theidea that EDNOS is too heterogeneousa category, because patients with thisdiagnosis differ more from each otherthan they do from AN and BN, respec-tively. Patients who have EDNOS andnarrowly miss criteria for AN and BNare often medically compromised andin need of treatment.

To our knowledge, this is the first pub-lished comparison of reported compli-cations among adolescents with EDfrom all DSM-IV diagnostic groups. Al-though patientswith AN certainly had ahigh rate of objective medical compli-cations observed during their firsthospital stays, the complication pro-files of other patients were hardly re-assuring. Patients with pAN and pBNalso displayed high rates of hospitalcomplications at �18% and 19%, re-spectively, and patients with BN andpBN reported significantly higher num-bers of serious complications beforepresentation than their peers with ANand pAN. Although additional prospec-tive study is required to confirm thesefindings, they suggest the need to de-lineate better the predictors of compli-cations and medical protocols in eachDSM group separately, rather thanmeasuring each group against an ANstandard.

Limitations of this study include that itis a clinical sample from a subspe-cialty ED program, which limits its gen-eralizability. It is also an exclusively fe-male sample, and although it is critical

that we learn better how to treat maleadolescents with EDs, this study doesnot inform that pursuit. Data were col-lected retrospectively; therefore, datamay be missing for nonrandom rea-sons not yet identified. In addition, clin-ical decisions that influenced thechoice of laboratory tests had beenmade, whichmay have introduced biason the basis ofmedical severity. In gen-eral, most variables were missing�10% of data, but phosphorus levels,electrocardiograms, and orthostatictesting were missing for 10% to 20% ofpatients, thereby necessitating cau-tion in the interpretation of thesevariables.

A limitation of any study of currentmedical hospitalization criteria for pa-tients with ED is that they were derivedfrom expert consensus and not fromlongitudinal study. Bradycardia, hypo-tension, orthostasis, and hypothermiahave clearly been shown in studies tobe strong indicators of a malnour-ished state and have therefore beenadopted as indicators of medical se-verity in patients with EDs.31,32 In addi-tion, QTc prolongation has been shownto be a risk factor for sudden cardiacdeath,36 which makes it the most con-cerning complication of the ones ex-amined here. However, we do not haveevidence that these findings mandatehospitalization and are not certain thathospitalization improves long-termmedical outcomes. It is possible that inthe future, outpatient treatment regi-mens may prove to be equally effective

and safe in treating these cardiacsequelae, and additional prospectivestudy is urgently needed to delineatethe most appropriate type of interven-tions and when they are indicated.

These analyses reveal that adolescentpatients with ED exist within a largerEDNOS group and aremedically similarto patients with AN and BN. They pro-vide a rationale to consider changes tothe diagnostic criteria for adolescentswith ED, as other authors have pro-posed.* For example, cut points ofweights, duration of behaviors, and en-docrine dysfunction are not currentlyevidence-based and thus may not betruly reflective of medical severity.47

Our study also suggests that currentcriteria for medical intervention maybe most appropriate for adolescentswith AN but that we may miss criticalopportunities for intervention and pre-vention in other ED groups.

Finally, our data propose another pos-sibility of diagnostic groupings, whichare shown in Fig 2, illustrating the orig-inal percentage of patients in AN, BN,and EDNOS categories and comparingthat with a new grouping in which pANand pBN are counted as a subgroup ofAN and BN, respectively. If patientswithpAN and pBN are combined into AN andBN groups, then only 14.3% of patientswith “true” EDNOS remain, similar toanother diagnostic reclassification ofadult patients with ED.38 If�60% of pa-tients have EDNOS by DSM-IV criteria,

*Refs 3, 4, 6, 9, 15, 16, 25, 26, and 37–46.

FIGURE 2DSM-IV and proposed diagnostic categories.

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then they are effectively forced into adiagnostic category that lacks defini-tion, health care coverage, or medicalknowledge.

CONCLUSIONS

In adolescents and children especially,EDs are a devastating set of diseaseswith multiple long-term sequelae. It isclear that a diagnosis of EDNOS doesnot imply a reassuring medical profile,and these findings underscore the

need to intervene early, even whenyoung patients do not meet full diag-nostic criteria for AN or BN. Futurestudies should be directed toward bet-ter defining the best clinical criteria bywhich we can intervene both medicallyand psychiatrically in these diverse setof illnesses.

ACKNOWLEDGMENTSThe project was funded in part bythe Stanford Child Health Research

Program; Ms Wilson received fund-ing from the Stanford MedicalScholars Research Program, andDr Lock received funding from Na-tional Institutes of Health grant K24MH074467.

We gratefully acknowledge Dr Iris Littfor support and help with editing ofthe manuscript and all of the re-search assistants at the StanfordWEIGHT laboratory who assisted withdata collection for this study.

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DOI: 10.1542/peds.2008-1777 2010;125;e1193-e1201; originally published online Apr 12, 2010; Pediatrics

Rebecka Peebles, Kristina K. Hardy, Jenny L. Wilson and James D. Lock Are Diagnostic Criteria for Eating Disorders Markers of Medical Severity?

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