Lesson of the Week: Occult intracranial tumours masquerading as early onset anorexia nervosa

Case reports CASE 1

An 8 1/2 year old boy presented with a six month history of intermittent headaches and vomiting. Clinical examination was unremarkable. A provisional diagnosis of migraine was made after unenhanced computed tomography of the brain showed nothing abnormal. Seven months after presentation the initial symptoms had settled but the patient had developed anorexia. Onset of physical symptoms coincided with the patient becoming introverted, emotionally labile, and periodically morose. His mother had died from a hepatocellular carcinoma when he was 3 years. The combination of unresolved grief, his father being admitted to hospital for a routine operation, and his eldest sister leaving home were thought to have precipitated this change in personality. He could not be coaxed into eating and was referred to a child psychiatrist, who diagnosed childhood onset anorexia nervosa with depression. Over the next nine months the patient continued solely under psychiatric follow up but with negligible improvement in weight gain or stature. His home environment was thought to be contributory, and, in view of these concerns, he was placed on the child protection register.

The patient was subsequently admitted to a second psychiatric unit for re-evaluation. Although clinically depressed, he was unresponsive to three months of psychotherapy. An endocrine opinion confirmed growth arrest both in terms of stature and weight. Despite having prolonged “anorexia,” he had normal skinfold thicknesses. Formal pituitary function tests showed isolated growth hormone deficiency and a high serum prolactin concentration of 841 mU/l (normal </=350 mU/l). Magnetic resonance imaging of the brain showed a craniopharyngioma. This was successfully resected, and the patient made an excellent recovery with immediate improvement in his mental state and resolution of his anorexia.

CASE 2

A 13 year old boy presented with a six month history of anorexia, nausea, difficulty in swallowing, and associated weight loss. Clinical examination and investigations, including barium studies, were normal. Both the patient's mother and maternal aunt had a history of anorexia nervosa in their adolescent and early adult years. The patient's mother had had symptoms for four years but eventually recovered when she met her future spouse. Although the boy had no apparent fear of fatness or distortion of body image, childhood onset anorexia nervosa was diagnosed after he had been referred to a child psychiatrist. He then underwent a stringent behaviour modification programme in hospital. During this period he was noted to have persistently dilated pupils, but visual acuity and peripheral fields were normal. There was, however, transient swelling of the optic discs. Unenhanced computed tomography of the brain showed only calcification of the pineal gland.

Nine months later the patient's condition deteriorated: he was extremely lethargic; he refused to eat, resulting in further weight loss; and he would vomit effortlessly, usually around meal times. He had also developed a right divergent squint but was not complaining of any other visual symptoms.

Psychiatric re-evaluation 10 months after presentation showed no evidence of a primary psychiatric disorder. Visual assessment confirmed a variable right divergent squint due to blindness in that eye and associated optic atrophy. Endocrine evaluation showed statural growth arrest, cortisol insufficiency, bio-chemical diabetes insipidus, and a high serum prolactin concentration of 7800 mU/l. Magnetic resonance imaging showed extensive enhancement of the optic nerves and chiasm, the hypothalamic area, the lower medulla, and upper spinal cord, as well as periventricularly. There was also considerable enhancement of the pineal gland. Diagnosis of a disseminating pineal germinoma was confirmed by stereotactic brain biopsy. The patient had an excellent clinical and radiological response to craniospinal irradiation and gained 12 kg in the six months after treatment.

CASE 3

A 7 year old boy was referred to our hospital with a three year history of progressive anorexia, recurrent episodes of vomiting, coughing, and discomfort on swallowing, and subsequent failure to thrive. Onset of symptoms had coincided with his father leaving home and his stepfather moving in with the family. Extensive investigation showed no organic cause for his symptoms, and computed tomography showed no abnormaility, although there was no imaging below the level of the foramen magnum. Although his symptoms were atypical for anorexia nervosa, the patient was thought to have a psychological eating disorder and received intensive psychiatric input, including a three month period as an inpatient. At the age of 9 years he developed vertical nystagmus. His gait had also become increasingly unsteady and school performance deteriorated. Tests of hypothalamopituitary function were normal. Magnetic resonance imaging showed a cervicomedullary tumour, which proved to be a low grade astrocytoma.

Discussion

Tumours affecting the hypothalamus (cases 1 and 2) and, rarely, those impinging on the brain stem (case 3) are recognised as causing both psychological dysfunction and anorexic symptoms without initial neurological signs.2 Diagnostic confusion with early onset anorexia nervosa has also been reported.2 In all three cases, there were coexistent psychosocial factors. Although intracranial disease was considered early on, this was thought to have been excluded by normal brain imaging. The computed tomography scans of all three patients were reviewed, and, even with hind-sight, were considered to be normal. In particular, there was no suprasellar calcification to suggest a craniopharyngioma (case 1), and in case 2 the calcified pineal gland was no more extensive than that found as a normal variant in up to 30% of pineal glands by the age of 15.3 Although scans of all three patients were unenhanced, magnetic resonance imaging may have proved more discriminating as an initial imaging technique. A high index of suspicion needs to be maintained even with normal neuroradiology, particularly in the presence of atypical clinical features, failure of response to treatment (case 1), or the development of new symptoms or signs (cases 2 and 3).

Childhood onset anorexia nervosa is rare. It is particularly unusual in boys, although several studies suggest that males may comprise a higher proportion (19 to 30%)4 5 of cases in childhood than they do in adolescence and adulthood (5 to 10%).6 Over the four years that these three cases presented we have seen a total of 20 boys referred with an eating disorder. Children may present with a variety of somatic symptoms, including feelings of nausea or fullness and difficulty in swallowing. Depressive symptoms may occur relatively early in children as weight loss tends to be more rapid and emaciation more profound.7

Careful anthropometric and endocrine assessment may give additional clues to the diagnosis. Although starvational states such as anorexia nervosa will stunt statural growth as well as weight gain, the finding of normal skinfold thicknesses (as in case 1), and thereby adequate subcutaneous fat stores, would be inconsistent with such a diagnosis.

In general, therefore, the diagnosis of childhood onset anorexia nervosa should not be entertained unless there is an overt and relentless pursuit of thinness, with an expressed aversion to putting on weight. Had these criteria been applied in the first two cases the diagnosis of anorexia nervosa could not have been made. Even when the diagnosis seems certain, however, a high index of suspicion should be maintained and re-evaluated as the presence of an eating disorder does not necessarily exclude a concurrent organic diagnosis. We recommend that any boy with anorexia should have careful anthropometric and endocrine assessment as well as neuroimaging, which may need to be repeated.

Neuroradiological review of the computed tomography scans from other centres was performed by Dr K Chong, consultant neuroradiologist, Great Ormond Street Hospital, to whom we are grateful.