obesitas kasus

case records of the massachusetts general hospital

T h e n e w e ng l a nd j o u r na l o f m e dic i n e

n engl j med 355;15 www.nejm.org october 12, 2006 1593

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From the Department of Pediatrics (A.G.H., E.S.K.), the Gastrointestinal Unit (L.M.K.), and the Department of Pathology (G.Y.L.), Massachusetts General Hospi-tal; and the Departments of Pediatrics (A.G.H., E.S.K.), Medicine (L.M.K.), and Pathology (G.Y.L.), Harvard Medical School.

N Engl J Med 2006;355:1593-602.Copyright © 2006 Massachusetts Medical Society.

Pr esen tation of C a se

A 15 1�2 -year-old girl was seen in the outpatient Weight Center of this hospital for the evaluation of severe obesity. She had had a normal gestation without complica-tions and had been adopted during the first month of life. She weighed 3.9 kg at birth and 4.8 kg at 1 month of age. At the age of 1 year, her weight-to-length ratio was in the 75th percentile. At 3 years of age, her body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was above the 97th percentile. She was referred to a nutritionist. Her appetite remained steady, and she ate most foods. Although her food intake appeared to be similar to that of the other children in the family, her BMI continued to increase (Fig. 1A).

Snoring and restless sleep began at approximately 5 to 6 years of age. At the age of 7 years, she was enrolled in a monthly weight-control program, and a year later, she was evaluated by a nutrition specialist. Physical examination revealed an overweight child with mild acanthosis nigricans of the neck with no other abnor-malities. The next year, her parents noted that she was eating secretly; hyperpig-mentation of the thighs was noted on physical examination. Between the ages of 10 and 11 years, her weight increased approximately 15 kg, and she began a pro-gram for weight control at her pediatrician’s practice. At 12 years of age, she was seen by a psychiatrist, who noted dysthymia and poor motivation and prescribed sertraline and psychotherapy.

When the patient was 13 years old, her parents noticed nocturnal somnam-bulation and an increased intake of food. At 13 years 3 months, the patient was referred to an endocrinologist because she had not lost weight and had chronic daytime fatigue. Her height was 162.4 cm, her weight 106.9 kg, her blood pres-sure 132/73 mm Hg, and her pulse 76 beats per minute. Breast development was Tanner stage 3, and pubertal development was Tanner stage 5 (with 1 representing immature development and 5 maturity); acanthosis nigricans was present around the neck and groin. The remainder of the examination was normal; there was no hirsutism. Results of laboratory tests are shown in Table 1.

Snoring and insomnia worsened during adolescence. Menarche occurred at the age of 14 years, and her menstrual cycles were irregular. Daytime sleepiness

Case 31-2006: A 15-Year-Old Girl with Severe Obesity

Alison G. Hoppin, M.D., Eliot S. Katz, M.D., Lee M. Kaplan, M.D., Ph.D., and Gregory Y. Lauwers, M.D.

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n engl j med 355;15 www.nejm.org october 12, 20061594

worsened, including falling asleep at school, and morning headaches developed. A combination of dextroamphetamine sulfate and amphetamine as-partate was prescribed to enhance alertness. Dur-ing an evaluation by a sleep specialist at the age of 14 years, physical examination revealed a blood pressure of 120/90 mm Hg; the tonsils were en-larged, but there was no marked crowding. A series of overnight polysomnograms obtained between the ages of 13 and 15 years showed progressive worsening of obstructive sleep apnea, including intermittent oxygen desaturation, hypercapnia, periodic leg movements, and sleep disruption. Bilevel ventilation therapy was started when the patient was 13 years old, but compliance with the therapy was poor. Pulmonary-function testing re-vealed normal spirometric values and lung vol-umes. The results of electrocardiography, chest radiography, and echocardiography were normal.

At the age of 14 years (17 months before this evaluation), the patient attended a summer camp and lost approximately 20 kg; she promptly re-gained the weight after returning home and gained an additional 12 kg during the subsequent year. Three months before presentation, she par-ticipated in a home-administered weight-loss plan

Figure 1. Changes in BMI over Time (Panel A) and Their Association with Specific Weight-Loss Treatments (Panel B).

Panel A shows a comparison of the patient’s BMI (indicated by X) with standard percentiles, according to age and sex. At all ages shown, the patient’s BMI is well above the 97th percentile for her age. Over the course of 3 years, various approaches were used to help the patient lose weight (Panel B). After the dis-continuation of sertraline, sibutramine was added, which was associated with a modest weight loss and no side effects. Over a period of 15 months, in con-junction with moderate-to-high levels of physical activ-ity, the patient lost 3.2 kg. As is typical with pharmaco-therapy for obesity, she regained the weight after stopping the drug. Metformin was begun for the treat-ment of diabetes, in conjunction with dietary counsel-ing. Treatment with orlistat was attempted but was dis-continued after only a few doses because of steatorrhea. At the age of 17 years, she participated in a group-based program at the Weight Center, consisting of be-havioral and nutritional interventions with a group of adolescents, with the parents meeting separately. The patient lost 3.2 kg during the 3-month course of the program and maintained the weight loss in the subse-quent 6 months.

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case records of the massachusetts gener al hospital


on the basis of a point system, but her weight con-tinued to increase.

At the time of the evaluation in the Weight Cen-ter, she had daytime somnolence but no head-aches. She drank low-calorie soft drinks and two glasses of juice daily. She snacked twice during the night on sandwiches or other carbohydrate-containing foods. She exercised with a personal trainer three to five times per week and watched television approximately 6 hours per day on week-

ends. She typically slept 7 hours on school nights and 12 hours per night on the weekends. She had no difficulty initiating sleep, but she was hard to arouse in the morning.

The patient’s early development had been nor-mal; she walked at 12 months of age and spoke in short sentences at 15 months. Her depression had improved after a change in schools during the year preceding her presentation at the Weight Center, and the psychotherapy was discontinued.

Table 1. Laboratory Values.*

Variable Normal Value Patient

8 Yr 2 Mo

13 Yr 3 Mo

13 Yr 3.5 Mo

15 Yr 6 Mo

Aspartate aminotransferase (U/liter) 0–35 25 41

Alanine aminotransferase (U/liter) 0–25 23 50

Alkaline phosphatase (U/liter) 0–322 287 74

Bilirubin (mg/dl) 0.2–1.0 0.4

Cholesterol (mg/dl) Desirable, <200 188 218

High-density lipoprotein 35–100 Normal 34

Low-density lipoprotein Desirable, <130 Normal 126

Triglycerides (mg/dl) 40–150 148 291

Prolactin (ng/ml) <18 5.7 8.4

Testosterone (pg/ml)

Free Woman, 1.1–6.3 Prepubertal girl, 0.2–0.6

7.3 3.3

Total Woman, 10–55 Prepubertal girl, <10

26

Dehydroepiandrosterone sulfate (μg/dl) 183–283 179.0

Estradiol (pg/ml) 30–500 22 50

Luteinizing hormone (IU/liter) Follicular, 2.1–12.2 8.9 3.5

Follicle-stimulating hormone (IU/liter) Follicular, 3.0–11.3 Prepubertal girl, <3.1

5.1 3.8

Sex hormone–binding globulin (μg/dl) Woman, 1.0–3.0 Prepubertal girl, 1.8–5.5

0.3

Thyrotropin (μU/ml) 0.3–6.2 2.1

Thyroxine (μg/dl) 5.3–10.9 6.6 6.8

Glycated hemoglobin (%) 3.8–6.4 5.8 6.7

Calculated mean blood glucose (mg/dl) 107 137

Glucose (mg/dl) 70–110 141

Fasting insulin (μU/ml) 3–12 106

Insulin (μU/ml) 0.0–20.0 166.5

* To convert values for bilirubin to micromoles per liter, multiply by 17.1. To convert values for cholesterol to millimoles per liter, multiply by 0.02586. To convert values for triglycerides to millimoles per liter, multiply by 0.01129. To convert values for thyroxine to nanomoles per li-ter, multiply by 12.87. To convert values for glucose to millimoles per liter, multiply by 0.05551. To convert values for insulin to picomoles per liter, multiply by 7.175.





She was a good student in the 10th grade. A grandmother in her birth family was known to have been overweight; no other biologic-family history was known. Members of her adoptive fam-ily, including her parents and two younger sib-lings, were of normal weight. Her only medication was sertraline, and she had no known allergies.

Her height was 164.5 cm, her weight 126.6 kg, and her BMI 46.7. The blood pressure was 124/95 mm Hg. Severe acanthosis nigricans was present on the neck and axillae, and there was moderate acne on the face; a slightly android pattern of hair growth was evident on the abdomen, and there were moderate striae on the lower abdomen. There was no hair growth on the face, no rash in the skin folds, and no edema. The remainder of the physical examination was normal.

Additional laboratory testing was performed (Table 1), and a plan for management was de-veloped.

Differ en ti a l Di agnosis

Dr. Alison G. Hoppin: This patient presented with un-common manifestations of a common disease. Obesity is common: 17.4% of adolescents in the United States are considered overweight by the standards of the Centers for Disease Control and Prevention.1 However, this patient’s degree of obe-sity was very unusual: with a BMI of 46.7, she had adiposity levels that constituted class 3 obesity (on a scale of 1 to 3, with class 1 indicating a BMI of 30.0 to 34.9, class 2 a BMI of 35.0 to 39.9, and class 3 a BMI of 40.0 or more) in an adult. In ad-dition, she had most of the important medical complications of obesity in children and adoles-cents (Table 2).

This patient’s most acute health issues at pre-sentation were symptoms suggestive of sleep ap-nea and diabetes mellitus. Because the symptoms of sleep apnea are somewhat subjective and there are no clear screening criteria, the problem is prob-ably underdiagnosed in children and adolescents with obesity.2-5 This patient was referred to Dr. Eliot Katz, a specialist in sleep disorders in chil-dren, who will discuss the evaluation and man-agement of her sleep apnea.

Obstructive Sleep Apnea

Dr. Eliot S. Katz: Testing of this patient by over-night polysomnography at 15 years of age (Fig. 2) indicated that her sleep latency was less than

4 minutes (normal, 9 to 33), suggesting objective sleepiness. She had recurrent episodes of partial or complete upper-airway obstruction associated with intermittent hypoxemia (minimum oxygen satu-ration, 86%; normal value, 92 to 96), hypercapnia (awake, 52 mm Hg, and asleep, 64 mm Hg; normal carbon dioxide peak during sleep, ≤53 mm Hg), and electroencephalographic arousal (Fig. 2). Her apnea–hypopnea index was markedly elevated at 21 events per hour (normal value, ≤1). Despite these findings, she had normal sleep architecture and sleep efficiency. Children with severe obstruc-tive sleep apnea often have normal distribution of sleep states, despite frequent episodes of ob-struction and brief electrocortical arousal.

Obesity poses both an obstructive load to the upper airway and an elastic load to the entire pul-monary system. Although pulmonary function, as measured by spirometry, is often normal in obese children during wakefulness at rest, as it was in this child, there are often measurable deficits dur-ing exercise and sleep. Obese children are 4.5 times as likely to have obstructive sleep apnea as are children who are not obese.19 The severity of the condition is related to the degree of visceral adiposity, rather than to the amount of total body fat. This patient had a central pattern of obesity, which has the strongest correlation with the meta-bolic syndrome.20 More than 90% of children with both obesity and habitual snoring have obstruc-tive sleep apnea.21 Thus, this patient probably had obstructive sleep apnea during her 8-to-10-year history of snoring before her initial polysom-nography. Androgens affect ventilatory control and increase visceral fat; thus, obstructive sleep apnea is more commonly seen in boys after pu-berty (rather than before puberty) and in women who have excessive levels of androgen associated with the polycystic ovary syndrome, which was suspected in this patient.22

SequelaeThe consequences of obstructive sleep apnea in-clude cardiovascular abnormalities, neurocogni-tive impairment, daytime sleepiness, and meta-bolic disturbances — several of which were seen in this patient. Her hypertension was probably a consequence of both obstructive sleep apnea and obesity. In extreme cases, biventricular dysfunc-tion and pulmonary hypertension may develop, and screening for pulmonary hypertension with echocardiography is indicated for children with





severe obstructive sleep apnea. The 8-to-10-year history of probable obstructive sleep apnea dur-ing a vulnerable period of brain growth places this patient at risk for neurocognitive impairment, including mood disturbance, which she had. The disease has a minimal effect on intelligence but may impair executive functioning and attention span and has been associated with poor school performance in adolescents.23

In contrast to adults with sleep apnea, most children do not have clinical or objective sleep-iness.24 Sleepiness in adolescents is frequently multifactorial and includes an insufficient amount of sleep, poor sleep hygiene, increased sleep re-quirements and circadian-rhythm disturbances, and disrupted sleep related to obstructive sleep apnea, sleepwalking, and nocturnal eating. Thus, this patient had many reasons for sleepiness.

Both obstructive sleep apnea and obesity are associated with increased levels of inflammatory markers,20,25 which are believed to be involved in

the normal homeostatic regulation of sleep. Thus, increased levels of circulating cytokines may con-tribute to the sleepiness that is characteristic of both obstructive sleep apnea and obesity. Ob-structive sleep apnea can increase insulin resis-tance and leptin levels, independent of obesity,20,25 and treatment with continuous positive airway pressure can reduce insulin resistance and levels of leptin and inflammatory markers.

TreatmentIn contrast to children of normal weight, obese children with adenotonsillar hypertrophy typically do not have complete resolution of obstructive sleep apnea after adenotonsillectomy, although their condition typically improves.26 In this pa-tient, nasopharyngoscopy demonstrated only mild adenotonsillar hypertrophy that was not consid-ered to warrant surgical removal. Weight loss can lessen the severity of obstructive sleep apnea, but residual obstruction is frequently present.27

Table 2. Important Health Effects of Obesity in Children and Adolescents.

DisorderDisorder Present

in the PatientOverall Prevalence

in ChildrenPrevalence in Obese

Children

percent

Obstructive sleep apnea Yes 1–32,3 13–364,5

Diabetes Yes

Type 2 diabetes mellitus6,7 <0.12 4

Impaired fasting glucose level8 7 18

Hypertension9* Yes 5 11

Dyslipidemia10 Yes

Triglycerides ≥110 mg/dl (1.2 mmol/liter) 23 52

High-density lipoprotein cholesterol ≤40 mg/dl (1.0 mmol/liter)

23 50

Polycystic ovary syndrome11,12 Yes 5–10 Increased

Fatty liver disease Yes

Steatosis (by ultrasonography)13 5 50

Inflammation (alanine aminotransferase >30 U/liter)14

2 15

Depression, social exclusion Yes

Orthopedic problems No

Slipped capital femoral epiphysis15 <0.1 About 0.5

Blount’s disease16 Not established Increased

Asthma17 No 11 15

Pseudotumor cerebri18 No <0.01 Increased in adolescents

* Hypertension is defined as a blood pressure in the 90th percentile or higher.





Continuous positive airway pressure and bilevel ventilation are both effective therapies for obstruc-tive sleep apnea.28 However, 15 to 20% of patients will not comply with the use of nasal positive-pressure ventilation at all; for the remainder of patients, the average duration of use is approxi-mately 5 hours per night. Although this patient acknowledged improvements in daytime func-tioning after receiving nocturnal bilevel ventila-tion, she complied poorly with therapy. Thus, her case illustrates both the consequences of sleep apnea and the difficulties in managing it.

Dr. Hoppin: This patient had features of the metabolic syndrome, a constellation of findings associated with an increased risk of atheroscle-rotic cardiovascular disease and type 2 diabetes mellitus.10

Insulin Resistance and Type 2 Diabetes Mellitus

This patient had evidence of insulin resistance, with severe acanthosis nigricans, an elevated in-sulin level after an overnight fast, and a glycated hemoglobin value of 6.7%. Subsequent testing

revealed a blood glucose level of 141 mg per deci-liter (7.8 mmol per liter) 2 hours after an oral glucose load (Table 1), documenting impaired glucose tolerance.29 Insulin resistance is inde-pendently associated with both obesity and pu-berty, so this patient is at risk for both reasons.6-8 In a longitudinal study of obese adolescents, pro-gression from normal to impaired glucose toler-ance occurred in 10% during a 2-year period, and 25% of these patients had progression to type 2 diabetes.30

Six months after the first visit, treatment with metformin was begun, in consultation with an endocrinologist. During the next 2 years, the pa-tient had a slight improvement in glycemic control, with glycated hemoglobin values ranging from 6.5 to 7% and fasting blood glucose levels between 90 and 95 mg per deciliter (5.0 to 5.3 mmol per liter). However, during a period of noncompliance with the metformin, her fasting blood glucose levels rose to a range of 244 to 275 mg per deci-liter (13.5 to 15.3 mmol per liter), diagnostic of diabetes mellitus.

Hypertension and Dyslipidemia

The patient had mild hypertension at her first visit, which gradually worsened during the next 18 months. Pharmacologic intervention is rec-ommended for hypertension that persists despite a modification in diet and for patients with dia-betes mellitus.9 Angiotensin-converting–enzyme inhibitors are recommended preferentially in children with diabetes. Treatment with lisinopril was initiated 18 months after her first visit. Her fasting total cholesterol and triglyceride levels were high, whereas the level of low-density lipo-protein cholesterol was in the borderline range. Our dietary counseling included recommenda-tions for a reduction in dietary fat.31

Polycystic Ovary Syndrome

The patient also had findings that suggested the polycystic ovary syndrome and nonalcoholic fatty liver disease, both of which are associated with the metabolic syndrome phenotype. The classic clinical features of the polycystic ovary syndrome include menstrual disturbance, hirsutism, and poly-cystic ovaries. However, on the basis of broader diagnostic criteria, the disorder is thought to af-fect 5 to 10% of women of reproductive age.11 Al-though the patient had menarche and menstrual patterns that could be considered normal and she

0 30 60 90

Seconds

Right EOG

Left EOG

O2-A1

Chin

Airflow

Chest

Abdomen

Leg

OxygenSaturation(%)

99

86

Figure 2. Sleep Study at 15 Years of Age.

A 90-second portion of an overnight polysomnogram obtained while the patient was in stage 2 sleep shows a series of episodes of obstructive ap-nea and hypopnea (arrows), characterized by a marked reduction in air-f low despite ongoing respiratory efforts. Accompanying the obstructive events are cyclic reductions in oxygen saturation of 5 to 10%. At the end of each obstruction is an arousal consisting of augmentation of electro-myographic tone and a frequency shift in the electroencephalogram. EOG denotes electrooculogram, and O2-A1 right occipital lead referenced to the left mastoid lead.





did not have marked hirsutism, she had an ele-vated level of free testosterone at 13 years of age, suggesting the presence of hyperandrogenism. Two years after her first visit here, she presented with acute right ovarian torsion due to a cyst. Dur-ing surgery to remove the cyst, the contralateral ovary was polycystic on gross examination, con-firming the diagnosis of the polycystic ovary syn-drome. After the operation, treatment with ethi-nyl estradiol and drospirenone was begun.

About 30% of adolescent girls with the poly-cystic ovary syndrome have glucose intolerance or diabetes mellitus.32 Hyperinsulinemia seems to be the common mechanism: insulin acts syn-ergistically with luteinizing hormone to increase the production of androgen by the ovarian theca cells while also decreasing the level of sex hor-mone–binding globulin.12,33 Treatment with metformin can lead to clinical improvement, even in adolescents without overt diabetes mel-litus.34

Nonalcoholic Fatty Liver Disease

On initial evaluation, mild elevations of serum aminotransferase levels were present, without hy-perbilirubinemia. Nonalcoholic fatty liver disease is the most common cause of mild aminotrans-ferase elevations in children and is strongly associ-ated with obesity and the metabolic syndrome.13,14 It is important to exclude other causes of liver disease, so when the finding persisted, we did labo-ratory testing to rule out viral hepatitis, autoim-mune hepatitis, and Wilson’s disease; all the test results were negative. No specific treatments have been established for fatty liver disease in chil-dren or adults, but weight loss is almost certain-ly helpful.

Causes of Obesity

We have discussed the consequences of the pa-tient’s obesity, but what can be said about the causes of it? Because she was adopted in early in-fancy, her case illustrates better than most how biologic determinants of obesity can dominate over lifestyle or environmental exposures, as Dr. Kaplan will discuss.

Dr. Lee M. Kaplan: In obesity, a combination of genetic, developmental, and environmental deter-minants alters the body’s normal system for the regulation of weight. The prevalence of obesity has increased in the past 50 years, with a dispro-portionate increase in severe obesity. Between 1986

and 2000, the prevalence of obesity (BMI >30) in-creased by a factor of 2, the prevalence of class 3 obesity (BMI >40) increased by a factor of 4, and the prevalence of the most severe forms of obe-sity (BMI >50) increased by a factor of 6.35,36

Most people are genetically susceptible to ab-normal weight gain under the right conditions. The availability of highly processed, calorie-dense foods and a decreasing level of physical activity are important environmental contributors to obe-sity, but they are not the only ones. Disrupted meal patterns, disordered and inadequate sleep, distur-bances in normal circadian rhythms, high levels of stress, social isolation, and the use of medica-tions that promote weight gain may be equally important. Several of these factors may have af-fected the patient, including sleep deprivation and the stresses of adolescence. In contrast, the con-tribution of her diet or pattern of eating to the obesity appears to be limited.

The early onset of obesity and the striking difference in weight between the patient and her adoptive siblings despite similar eating habits sug-gest an important contribution of genetics to her obesity.37,38 There is strong evidence that genetic background plays an important role in determin-ing the predisposition to obesity. Obesity often runs in families, and the correlation of BMI among siblings is little affected by whether they were raised together or apart and is often independent of the type or pattern of food intake or physical activity. Studies of twins suggest that genetic fac-tors determine about 50 to 70% of the predispo-sition to the development of obesity.39

We have little information about the biologic relatives of the patient, other than that her grand-mother was overweight. Although the onset of her obesity was very early, most of the known mono-genetic or oligogenetic causes of obesity are un-likely.40 These rare disorders reflect alterations in genes that encode central nervous system regu-lators of body weight, such as leptin, the leptin receptor, melanocyte-stimulating hormone, and the melanocortin 4 receptor (MC4R). Genetic test-ing through a research protocol revealed no evi-dence of an abnormal MC4R in the patient. The plasma leptin level was 47 ng per milliliter (nor-mal range, 3.3 to 18.3); the elevated level was ap-propriate to her obesity, thereby excluding genetic deficiency in leptin or its receptor. Symptoms of the most common, well-defined obesity syndromes — including the Prader–Willi syndrome, the Bar-





det–Biedl syndrome, and a deficiency in single-minded homologue 1 (SIM-1) — were absent.

Many genes contribute to the regulation of body weight, and a genetic predisposition to obe-sity, which the patient and other children with early-onset obesity almost certainly have, prob-ably results from the influence of multiple genes, which combine to support an energy-thrifty phe-notype.41

Discussion of M a nagemen t

Weight-Loss Strategies

Dr. Hoppin: Despite the likelihood of a strong bio-logic basis for the patient’s obesity, there is no specific physiological target that we can address to facilitate her weight management. The patient had lost approximately 20 kg in weight while at-tending a summer weight-loss camp 17 months before presentation to the Weight Center; she rapidly regained this weight after returning home. Such rebounds after acute weight loss from di-etary restriction are very common and probably speak to the resilience of weight-regulatory mecha-nisms rather than to bad habits or a failure of willpower. Thus, we believed that the lifestyle hab-its of the patient and family were not the primary cause of her obesity. Nonetheless, our first ap-proach was to work with her and her family to optimize these habits.

This patient embarked on a new series of weight-control attempts, with limited success (Fig. 1B). She continued to work with a personal train-er, engaging in aerobic and strength training 3 days a week, and received dietary supervision from the trainer, supplemented by individual nu-tritional counseling from a registered dietitian. She was able to stabilize her eating patterns to some degree, and the frequency of nocturnal eat-ing decreased. After her first visit, sertraline was tapered and then discontinued, and a trial of sibutramine was begun 2 months later. Metfor-min was added 4 months later for glycemic con-trol. With these combined therapies, her weight gain stopped, but she lost only 3.2 kg during the first year, and sibutramine was ultimately with-drawn.

When she was 17 years old, she participated in a group-based program at our center with weekly meetings for 3 months. The group con-sisted of adolescent girls with obesity and was led by a dietitian. Specific goals were to improve

food choices and planning and included both nutritional education and behavioral techniques. Dietary guidelines included modest caloric re-striction and a relatively low intake of simple carbohydrates. The parents of the girls met con-currently with a psychologist to address family dynamics related to weight control. The patient participated actively and enthusiastically in the group program; she reduced her weight by an-other 3.2 kg and maintained the weight loss dur-ing the subsequent 6 months.

Three years after her first evaluation, the pa-tient had maintained a 6.8-kg weight loss for about a year. However, her BMI of 44 remained in

A

B

Figure 3. Liver-Biopsy Specimen Obtained during Gastric Bypass Procedure.

Panel A shows marked diffuse macrovesicular steatosis with inflammation (arrows) and ballooning degenera-tion of hepatocytes (inset, arrow) (hematoxylin and eo-sin). Panel B (trichrome stain) shows extensive fibrosis with bridging between portal areas; fine pericellular fi-brosis is seen at a higher magnification (inset). In the absence of a history of alcohol use or other liver dis-ease, the presence of fat is characteristic of nonalco-holic fatty liver disease. The presence of inflammation and fibrosis indicates progression to nonalcoholic ste-atohepatitis.





the range of severe obesity, and she continued to have sleep apnea, diabetes mellitus, hypertension, and dyslipidemia.

Bariatric Surgery

When the patient was 18 years old, we began to consider the possibility of weight-reduction sur-gery. Gastric bypass is clearly the most consis-tently effective treatment for severe obesity in adults42,43; although less is known about out-comes in adolescents, a few published case series suggest that they are similar to those in adults.44 An expert panel45 has recommended that weight-reduction surgery be considered for adolescents with a BMI of more than 40 who have severe medical complications of obesity (such as sleep apnea or diabetes, as in this patient) or with a BMI of more than 50 who have any medical compli-cations and in whom efforts to control weight through other measures have been unsuccessful. In adolescents, medical follow-up to monitor for and treat potential micronutrient deficiencies is essential.46

The patient was an appropriate candidate for bariatric surgery. Her weight and coexisting ill-nesses were appropriate indications according to criteria for both adults and adolescents. She had made a variety of sustained efforts to control her weight by other measures, and she had an excel-lent record of compliance with long-term medi-cal follow-up.

At the age of 19 years, the patient underwent a laparoscopic Roux-en-Y gastric bypass. Her ini-tial postoperative recovery was uncomplicated. A

wedge biopsy of the liver was performed during the operation.

Dr. Gregory Y. Lauwers: The liver biopsy showed histologic evidence of nonalcoholic steatohepa-titis (Fig. 3). The condition is characterized by in-flammation and fibrosis, indicating damage to hepatocytes, and is considered to be a progres-sive form of nonalcoholic fatty liver disease. It has the potential to progress to cirrhosis and hepa-tocellular carcinoma, but the magnitude of the risk is not known.47

Dr. Lynne L. Levitsky (Pediatric Endocrinology): At her most recent follow-up, 1 month after sur-gery, the patient’s weight had decreased from 122.5 kg to 109.6 kg, with a BMI of 39.8. Met-formin and lisinopril had been discontinued at the time of the surgery. The blood pressure was 138/79 mm Hg, and her morning blood glucose levels by finger-stick measurement had been nor-mal on all but two occasions. On physical exami-nation, acanthosis nigricans that had developed on the wrists and ankles had resolved but per-sisted on the neck.

A nat omic a l Di agnosis

Severe childhood obesity with obstructive sleep apnea, hypertension, impaired glucose tolerance progressing to type 2 diabetes mellitus, the poly-cystic ovary syndrome, and nonalcoholic steato-hepatitis.

Dr. Hoppin reports having received grant support from the Massachusetts Vitamin Litigation Fund. No other potential con-flict of interest relevant to this article was reported.

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Lantern Slides Updated: Complete PowerPoint Slide Sets from the Clinicopathological Conferences

Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a teaching exercise or reference material is now eligible to receive a complete set of PowerPoint slides, including digital images, with identifying legends, shown at the live Clinicopathological Conference (CPC) that is the basis of the Case Record. This slide set contains all of the images from the CPC, not only those published in the Journal. Radiographic, neurologic, and cardiac studies, gross specimens, and photomicrographs, as well as unpublished text slides, tables, and diagrams, are included. Every year 40 sets are produced, averaging 50-60 slides per set. Each set is supplied on a compact disc and is mailed to coincide with the publication of the Case Record.

The cost of an annual subscription is $600, or individual sets may be purchased for $50 each. Application forms for the current subscription year, which began in January, may be obtained from the Lantern Slides Service, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114 (telephone 617-726-2974) or e-mail [email protected].



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