PSYCHIATRY

An Overview of the Etiology, Diagnosis, and Management of Anorexia Nervosa

Neville Golden, MD, Ira M. Sacker, MD

The incidence of anorexia nervosa is increasing in adolescents. The pediatrician caring for t^nagers is often the first professional confronted with the early signs and symptoms of this disorder. Clinical features and available literature on the psychological, nutritional, and family disorganization found in patients with anorexia nervosa are reviewed. Different therapeutic approaches are discussed, and current data on outcome are presented.

LNOREXIA NERVOSA was first described in 1689 by an English physician, Richard Morton,' who called it "a nervous consumption," but it was not recognized as a clinical entity until the independent descriptions by Gull in England^ and Lasegue in France in 1873.' Gull coined the term 'anorexia nervosa,' which has persisted despite the fact that it is a bit of a misnomer. Many of these patients are not anorexic, but rather they experience intense feelings of hunger that they either actively deny or fulfill by abnormal eating habits. The condition is primarily seen in young girls (about 10% of cases are male) and is associated with voluntary self-starvation and emaciation, a persistent fear of being fat, a distorted body image, and a relentless pursuit of thinness. These young girls often have a characteristic premorbid personality associated with a par-

ticular family set-up, and they develop definite endocrine abnormalities, mainly at the level of the hypothalamus. These can be detected both clinically and on laboratory testing. In our society, we emphasize thinness, and anorexia nervosa seems to be on the rise.^ There is a very significant mortality of between 5^ and 20 percent."^ Feighner et alP have outlined necessary diagnostic criteria: 1) Age of onset prior to 25 years; 2) Anorexia with weight loss of at least 25 percent of original body weight; 3) A distorted attitude towards eating, food, or weight that overrides even the instinctive responses to hunger and threats; (These first three criteria may be associated with the following characteristics: denial of illness; apparent enjoyment in losing weight; a desired body image of extreme thinness, and unusual avoiding or handling of food.) 4) No known medical illness that would account for the extreme loss of weight; 5) No overt psychiatric illness; and

From the Section of Adolescent Medicine. Department of Pediatrics. Brookdale Hospital Medical Center. State University of New York, Brooklyn, New York. Correspondence to: Neville Golden. MD. Department of Pediatrics, Brookdale Hospital Medical Center, State University of New York, Brooklyn, NY 11212. Received for publication May 1983. revised June and September 1983, and accepted November 1983. CLINICAL PEDIATRICS April 1984

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6) At least two of the following conditions: amenorrhea, lanugo, bradycardia (persistent resting pulse <60), hyperactivity despite severe weight loss, bulimia, and self-induced vomiting. Premorbid Personality These young girls are described as having been "perfect childreri" prior to the illnesscompliant, very successful academically, well liked by their peers, and good athletes. They are usually of average or above average intelligence. Further analysis, however, shows them to be over-achieving, obsessive, dependent, and psychosexually inadequate. Family Background Anorexia nervosa patients often come from upper middle-class families with high achievement orientation. One of the parents, usually the mother, tends to be dominant and over-protective, while the other parent is weak, submissive, and often absent from the home for long periods of time. In a review of the charts of 34 anorexics, Beumont el al.^ found that in just over half the patients, at least one of the parents worked in one of the caring professions (doctors, psychologists, nurses, ministers of religion). The patient's family is ostensibly stable with few broken marriages. The parents are proud of both their family and their child and expect obedience and success from her. What then causes the disintegration of this apparent harmony? Adolescence is a time of changing body image, emotional turmoil, and, hopefully, the attainment of self-identity. These previously over-compliant children have always accepted standards imposed on them by others, and now they find tremendous difficulty in attaining their own identity. They are dependent on their mothers, but at the same time, they struggle for independence from their mother's control. Feelings of hostility toward their mothers are associated with guilt and anxiety, and may result in the adolescent's denial of her own sexuality. Hilda Bruch describes the anorexic's tremendous fear of loss of control. By losing weight, she gains control of her own body and, ultimately, control of the dynamics of the entire family. The anorexic patient never really resolves the tasks of adolescence and continues to function in the style of early childhood with the persistence of egocentricity. She is unable to think abstractly, and her thoughts and actions tend to be of a concrete nature. Although the physical and psychological consequences of severe malnutrition dominate the clinical picture, the primary

disorder is related to deficiencies in the sense of self, identity, and autonomy. Nutritional Disorganization Some investigators have found that the majority of patients are premorbidly overweight,"* but this is not always the case. In one study described by Bruch,^ only six of 45 anorectic patients had a weight above 140 pounds. One third of the patients were described as "slightly plump," but the vast majority were of normal weight for height and age at the onset of disease. Nutritional disorganization is characteristic of this disorder and may be manifested in two forms: a) refusal to eat and b) uncontrolled impulse to binge without being aware of hunger. This may be associated with purging and abuse of laxatives and diuretics. Anorectic patients are preoccupied with food, and they enjoy preparing meals for others. They deny their hunger sensations and complain of abdominal pain and bloating after eating even small portions of food. Many refuse to eat with other family members. They often dispose of food down the toilet, and they may go to excessive lengths to hide their vomiting. They are well read in lay nutrition, obsessively maintain calorie intake charts, and tend to maintain a diet rich in protein and vitamins. Not all anorectic patients are bulimic, and bulimia exists as a distinct syndrome in women who are not anorectic. "Bulimia" is the condition whereby an individual repeatedly loses control of the impulse to binge and rapidly consumes a largeamount of food in a short period of time. Vomiting is then self-induced in an attempt to lose weight. By definition, in anorexia nervosa, a weight loss of 25 percent of original body weight is necessary for diagnosis, while bulimia can occur at any body weight. In four independent reviews,'""''^ each studying more than 100 patients with the diagnosis of anorexia nervosa, bulimia was found in approximately 40 percent of the patients. Some authors" believe that bulimia represents a distinct subgroup of anorexia nervosa. The more prevalent feeling, however, is that anorexia nervosa and bulimia represent a spectrum of eating disorders.'-^ Clinical Picture The primary feature of anorexia nervosa is severe weight loss in excess of 25 percent of previous body weight, but despite this emaciated condition, the patients exhibit endless energy. Most investigators have
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found amenorrhea to be a consistent finding, and this may even preceed the weight reduction. Physical examination may reveal dry skin, the presence of lanugo hair over the back and extremities, hypotension, hypothermia, and bradycardia. Edema may be present, especially after refeeding. The breasts are atrophic and the uterus is small, but the distribution of pubic and axillary hair is normal. Laboratory values are nonspecific; Anemia is an uncommon finding despite the malnutrition, but leukopenia, with a relative lymphocytosis, is seen frequently. Electrolyte abnormalities may be evident, especially in the presence of vomiting or abuse of laxatives and diuretics. Blood glucose levels may be low, normal, or elevated, and the glucose tolerance test may be flat or diabetic in nature. Total protein and albumen levels are normal. Some patients may exhibit low plasma Vit A levels, and hypercarotinemia is a frequent finding, the basis of which is unknown.
Endocrine Abnormalities

many malnourished states and appears to be a protective mechanism to decrease the body's oxygen consumption. This is not specific to anorexia nervosa.
Gonadotropin Secretion

Investigators have found abnormalities in thermoregulation, thyroid function, and the secretion of gonadotropin, cortisol, growth hormone, and vasopressin. These findings, together with the eating disorder and amenorrhea, have led to the belief in a hypothalamic disorder. Some of these abnormalities will be considered briefly.
Thermoregulation

Basal plasma levels of follicular stimulating hormone (FSH), luteinizing hormone (LH), and estradiol have been found to be consistently low,""^^ and administration of gonadotropin releasing hormone (GnRH) results in a delayed rise in plasma FSH and LH levels."'^' Both of these abnormalities are resolved on resumption of normal body weight. In normal individuals, the administration of clomiphene citrate stimulates gonadotropin release by competing with endogenous estrogen and testosterone feedback at the hypothalamic receptor sites. In patients with anorexia nervosa, clomiphene administration does not increase plasma FSH and LH levels,'^'^^ which further implicates a hypothalamic defect. This, too, reverts to normal after adequate weight gain and seems to be inextricably linked with the malnutrition.
Growth Hormone

Resting levels of growth hormone (GH) may be significantly elevated,'^'^^ and they appear to be higher in patients with a low calorie intake. The majority of patients respond to at least one ofthe GH stimulation tests, implying normal pituitary function.
Adrenal Function

Patients with anorexia nervosa exhibit abnormal responses to exposure to heat and cold when compared with control subjects.'*'^ These changes are reversible with restoration of normal body weight. As the hypothalamus is primarily responsible for thermoregulation, this evidence suggests hypothalamic dysfunction.
Thyroid Function

Basal plasma cortisol levels tend to be elevated in patients with anorexia nervosa,'*'^* and there may be a loss of diurnal variation.^^ Boyar et al.^^ demonstrated a normal production rate of cortisol but a prolongation of the cortisol half-life associated with decreased metabolic turnover. Similar findings have been demonstrated in patients with protein calorie malnutrition.'^''
Vasopressin

Amenorrhea, dry skin, constipation, bradycardia, and low basal metabolism rate suggest that these patients might be hypothyroid, but most investigators have found normal levels of thyroxine (T4) and thyroid stimulating hormone (TSH). Administration of thyrotropin releasing hormone to patients with anorexia nervosa results in increased plasma TSH levels, but the peak response tends to be delayed.'* Serum triiodothyronine (T3) levels have been found to be low, and this is accompanied by a corresponding increase in its metabolically inactive mirror-image form, reverse T3. This may be due to deficient peripheral deiodination of T4 to T3.' A similar situation is found in
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Four offivepatients tested in Mecklenberg's series'* and 44 percent of patients in Vigersky's series^'^ demonstrated a defective urinary concentrating mechanism, indicating partial diabetes insipidus. This responded to exogenous vasopressin administration and is further evidence to support a hypothalamic dysfunction in anorectic patients.
Pathogenesis

In light of the above findings, can we better understand the pathophysiology of this condition? We

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know that some of the endocrine abnormalities can be explained on the basis of malnutrition, weight loss, and low calorie intake, and similar findings have been found in other malnourished states. Other findings, however, are indicative of an independent hypothalamic dysfunction. Is the hypothalamic insult secondary to the mental disorder or to starvation itself, or could this be a primary hypothalamic disorder of unknown etiology? This problem has been discussed at length elsewhere,''''^*'^ but at this stage, it is probably simplistic to theorize on a particular sequential pathogenesis. It is clear that the mental disorder, the hypothalamic dysfunction, and malnutrition can individually result in some of the clinical manifestations of anorexia nervosa, and the total picture is probably a result of an intricate interaction of all three mechanisms. In an attempt to explain both the psychiatric and hypothalamic dysfunction on a molecular level, Barry and Klawans^' have proposed an abnormality of neurotransmitter regulation, postulating that many ofthe manifestations of anorexia nervosa can be explained on the basis of increased activity of dopamine at central dopamine receptors in the brain. This postulated increased dopaminergic activity may play a role in the pathogenesis of anorexia nervosa, but further research is required to elucidate the matter. Treatment Treatment is aimed at restoring normal nutrition and body weight, resolving psychiatric abnormalities, and maintaining body weight and a state of well being over a long-term period. Most investigators feel that medical admission into a hospital is necessary for the initial weight gain. This additionally serves to remove the patient from her home environment, provides good supportive nursing care, and allows the initiation of psychotherapy. Starvation itself causes psychological disorganization, and in the malnourished state, it is very difficult to accomplish effective psychotherapy. In the literature, however, there are no treatment studies comparing the effectiveness of initial inpatient management with that of an outpatient program. Halmi^ has suggested that initial outpatient therapy may be successful in adolescents who fulfill the following criteria: those who have had anorexia nervosa for less than four months, those who are not binging or vomiting, and those who have parents who are cooperative in family therapy. There are several approaches to treatment. Many regimens

utilize a multifaceted approach incorporating medical management for nutritional restoration, individual psychotherapy, and family therapy aimed at the dysfunctional family unit. The patient is admitted to a general pediatric floor, and medical management is aimed at correction of electrolyte abnormalities and the restoration of body weight. Weight gain should not be encouraged at too rapid a pace as this may result in edema, congestive cardiac failure,^^ acute gastric dilatation,'***' or precipitate confusion, depression, and even suicide,'^ Weight gain of a quarter to half a pound per day is recommended, and the involvement of a qualified nutritionist is advisable. Daily weights, intake and output charts, and calorie counts should be monitored. Serum electrolytes should be followed closely, especially in those patients who have been vomiting or abusing laxatives. In the medical management of anorexia nervosa, behavior modification is a very efficient means of restoring life-threatening weight loss without resorting to tube feeding or intravenous Buids, It is based on operant conditioning with reward dependent on weight gain,'^''"* Weight loss results in loss of privileges, A contract is agreed upon by both the physician and the patient with a certain predetermined weight gain expected of her. Initially, the patient is placed in an empty room with no visitors, no television, no telephone, and no bathroom privileges. Privileges are earned by appropriate daily weight gain. Treatment should always be accompanied by psychotherapy to correct the basic underlying psychiatric problem. Psychotherapy should be performed by a psychiatrist with expertise in treating anorexics. Probably the most difficult aspect of this is dealing with the patient's denial and helping her develop an awareness of her own feelings in order that she may attain her own identity and autonomy. Psychotherapy should be initiated while the patient is still in the hospital and often needs to be continued for months to years, Minuchin and co-workers'*~'' stress the importance of the dysfunctional family unit and the necessity to address this in the treatment of anorexics. Anorexics, as well as adolescents with psychosomatic disorders, have been studied, and a very definite pattern of organization within these families has been detected. Such families exhibit the characteristics of enmeshment, overprotectiveness, rigidity, and lack of conflict resolution. In addition, the child appears to be involved in the parental conflict in such a way that she can detour, avoid, or suppress the conflict. Furthermore,
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the patient's illness plays a role in maintaining family homeostasis. This type of family tends to support somatic expression and anorectic behavior.^^ Family therapy is aimed at restructuring the dysfunctional family system. While still in the hospital, family lunch sessions are held where the patient, her parents, and siblings are present, and the therapist can observe the family interactions in response to the eating habits of the patient. The therapist intervenes where necessary, and the ultimate aim is to restructure the family group. On discharge of the patient, the family is given tasks to carry out at home, and a behavior modification program is continued outside the hospital. Family therapy deals with the anorectic's symptoms and with the parents' marital problems and usually has to be continued for at least 6 months. Using such a program with 53 anorexics, Rosman et alr"^ were successful in 88 percent of their patients. Pharmocotherapeutic adjuncts to treatment utilizing phenothiazines,^* antidepressants,'^ cyproheptadine,*"* and metochlopramide"" have been discussed elsewhere, but further studies are required to demonstrate their improved effectiveness over other regimens. The modalities described above have been used singly and in combination, and the success rate for initial restoration of body weight is high, irrespective of the method employed. With weight gain, there is a reversal of many of the hormonal abnormalities. Russell"*^ has discussed the problems associated with comparisons between the different treatment programs. Probably the largest variable is patient selection. In addition, many of the studies either utilize too small a number of patients, or the patients are receiving more than one modality of treatment. Better designed, well-controlled studies with follow-up extending for at least 4 years are required before reasonable inferences can be made.
Outcome and Prognosis

no.stic index. The EAT may prove to be a useful instrument in evaluating outcome after discharge from the hospital. In comparing the outcome of anorexics from different series, one has to consider patient sampling, length of follow-up, and the parameters being assessed (for example body weight, menstrual history, eating difficulties, or psychiatric outcome). Hsu''^ reviewed the literature from 1954 to 1978, and the combined results showed that at least 75 percent of the patients had shown improvement in body weight (body weight at least 75% of average) at followup of at least 2 years, but only one third were eating normally. The remaining patients were still avoiding higher calorie foods and 14 to 50 percent had become bulimic. One half of those showing improvement in body weight were menstruating at follow-up. This usually occurred after improvement of the psychiatric disorder and attainment of a certain minimal weight for height.''^ Between one half and two thirds of the patients, however, still suffered from psychiatric symptoms. Long illness before admission, later age of onset, a distorted family background, and bulimia tend to be associated with a poorer prognosis.""^ In adolescents with anorexia nervosa, death may occur as a result of inanition, infection, suicide, and cardiac arrest, probably on the basis of electrolyte abnormalities. Hsu'sfigures'*"*reveal that despite initial improvement in the condition, 25 to 50 percent of these patients experience a relapse and up to 38 percent require medical readmission with 2 years. It is evident that anorexia nervosa tends to be a chronic condition, and long-term psychotherapy and follow-up are required even after apparent improvement.
Acknowledgments The authors would like to thank Mrs. Marsha Nager for lier secretarial assistance.

References

It is widely recognized that most patients gain weight on admission to the hospital irrespective of the treatment modality utilized. Russell, however, points out that their initial response to in-hospital treatment does not predict the ultimate outcome.""^ Recently, Garner and Garfinkef^'"''' developed a self-report Eating Attitudes Test (EAT), which appears to be a reliable objective measure of the symptomatology of anorexia nervosa. They suggest that both the initial EAT score and the score after treatment may be used as a progCLINICAL PEDIATRICS April 1984

1. Morton R. Phlhisiologica; or a treatise of consumptions. Printed for Sam Smith and Benjamin Walford al the Prince's Arms in St. Paul's Churchyard. London. 1689. 2. Gull WW. Anorexia hysteria (Apepsia hysteria). Br Med J 1873;2;527. 3. Lasegue C. On hysterical anorexia. Med Times Hosp Gaz 1873;2:265. 4. Grisp AH. Palmer RL, Kalucy RS. How common is anorexia nervosa? A prevalence study. BrJ Psychiatry 1976; 128:54954. 5. Frazier SH. Anorexia nervosa. Dis Nerv Syst 1965;155-9. 6. Theander S. Anorexia nervosa. A psychiatric investigation of 96 female patients. Acta Psychiatr Scand [SuppI] 1970;214;l-194. 7. Feighner JP. Robins E. Guze SB, et al. Diagnostic criteria for

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26. Russell GFM. The present status of anorexia nervosa. Psychol Med 1977;7:363-7. 27. Barry VC, Klawans HL. On the role of Dopamine in the pathophysiology of anorexia nervosa. J Neural Transm 1976;38:107-22. 28. Halmi KA. Treatment of anorexia nervosa: a discussion. Journal of Adolescent Health Care 1983:4:47-50. 29. Powers PS. Heart failure during treatment of anorexia nervosa. Am J Psychiatry 1982; 139:1167-70. 30. Russell GFM. Acute dilatation of the stomach in a patient with anorexia nervosa. BrJ Psychiatry 1966; 112:203-7. 31. Jennings KP, Klidjian AM. Acute gastric dilatation in anorexia nervosa. Br Med J 1974;2:477-8. 32. Bruch H. Perils of behavior modification in treatment of anorexia nervosa. JAMA 1974;230:1419-22. 33 Halmi KA, Powers P, Cunningham S. Treatment of anorexia nervosa with behavior modification. Arch Gen Psychiatry 1975;32:93-6. 34 Agras S, Werne J. Behavior modification in anorexia nervosa: research foundations. In: Vigersky RA, ed. Anorexia nervosa. New York: Raven Press, 1977:291-303. 35 Minuchin S, Baker L, Rosman BL, et al. A conceptual model of psychosomatic illness in children. Family organization and family therapy. Arch Gen Psychiatry 1975;32:1031-8. 36 Rosman BL, Minuchin S, Baker L, et al. A family approach to anorexia nervosa. Study, treatment and outcome. In: Vigersky RA, ed. Anorexia nervosa. New York: Raven Press, 1977:341-8. 37. Liebman R, Minuchin S, Baker L. An integrated treatment program for anorexia nervosa. Am J Psychiatry 1974;131:432-6. 38 Dally PJ, Sargant W. A new treatment of anorexia nervosa. Br MedJ 1960; 1:1770-5. 39 Mills I. Amitriptyline therapy in anorexia nervosa. Lancet 1976;2:687. 40 Halmi KA, Falk JR. Cyproheptadine, an antidepressant and weight-inducing drug for anorexia nervosa. Lancet 1982;l:1357-8. 41. SalehJW, Lebwohl P. Metochlopramide induced gastric emptying in patients with anorexia nervosa. Am J Gastroenterol 1980;74:127-30. 42 Russell GFM. General management of anorexia nervosa and , difficulties in assessing the efficacy of treatment. In: Vigersky RA, ed. Anorexia nervosa. New York: Raven Press, 1977:277-89. 43 Garner DM, Garfinkel PE. The Eating Attitudes Test: an index of the symptoms of anorexia nervosa. Psychol Med 1979;9:273-9. 44. Garner DM, Olmsted MP, Bohr Y, et al. The Eating Attitudes Test: psychometric features and clinical correlates. Psychol Med 1982;12:87I-8. 45 Hsu LKG. Outcome of anorexia nervosa. Review of the literature (1954 to 1978). Arch Gen Psychiatry 1980;37:1041-6. 46 Wentz AC. Body weight and amenorrhea. Obstet Gynecol 1980;56:482-7.

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