European Journal of Endocrinology (2008) 159 S95–S99

ISSN 0804-4643

‘Do no harm’: management of craniopharyngioma
Helena Gleeson, Rakesh Amin and Mohamad Maghnie1
Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester M27 4HA, UK and 1Department of Paediatrics, IRCCS,
Giannina Gaslini, University of Genova, Genova, Italy
(Correspondence should be addressed to H Gleeson; Email: helena.gleeson@cmmc.nhs.uk)

Abstract
Craniopharyngioma management is challenging. Although histology is benign, the tumour can be
clinically aggressive with local invasion and frequent recurrences. Extensive morbidity may be present
at diagnosis and furthermore, occurs as a consequence of neurosurgery and radiotherapy.
Hypothalamic symptoms can have a devastating effect on quality of life and may reduce life
expectancy. This case highlights both the challenge of managing hyperphagia and morbid obesity and
the importance of initial treatment preserving existing hypothalamic function and the need to avoid
tumour recurrence and further surgery.
A 11-year old boy presented with hydrocephalus secondary to a craniopharyngioma (he had visual
failure and hypopituitarism but few hypothalamic symptoms). He underwent radical resection followed
by radiotherapy. Following this treatment, he developed psychological and behavioural problems and
hyperphagia. Weight gain in the first year (an increase from C1.4 to C3.7 S.D.) resulted in poor
mobility and a fall which caused a slipped femoral epiphysis. In the next year, there was a 6-month
period of unexpected weight loss (C4.2 to C3.8 S.D.) that culminated in emergency treatment for
diabetic ketoacidosis secondary to severe insulin resistance. He developed a left hemiplegia, and a
subsequent cerebral angiogram identified multiple stenoses of the Circle of Willis with a Moyamoya
appearance secondary to radiotherapy. Weight gain has continued (C3.8 to C5.5 S.D.) so that
bariatric surgery is a management option.
European Journal of Endocrinology 159 S95–S99

Introduction
‘There is perhaps no other primary brain tumour that
evokes passion, emotion, and as a result, controversy
than does the craniopharyngioma’ (1).
Craniopharyngioma is a histological benign epithelial
intracranial lesion arising from the remnants of the
Rathke’s pouch. Despite its benign microscopic appearance, it can be clinically aggressive with the signs of
invasion and a high incidence of recurrence. Although
more common in adults, when the papillary form
predominates, craniopharyngioma is the commonest
pituitary mass in children (2, 3) and represents 6–13%
of paediatric brain tumours with a peak incidence between
5 and 10 years of age (4). The most frequent histological
type in childhood is adamantinomatous, which arises from
neoplastic transformation of embryonic squamous cell
nests of the involuted craniopharyngeal duct that initially
connects Rathke’s pouch with the stomodeum (5, 6).
We report a case that highlights the significant morbidity associated with the diagnosis of craniopharyngioma,
This paper was presented at the 5th Ferring International Paediatric
Endocrinology Symposium, Baveno, Italy (2008). Ferring Pharmaceuticals has supported the publication of these proceedings.

q 2008 European Society of Endocrinology

the sequelae of treatment with neurosurgery and
radiotherapy, and the challenges for the endocrinologist
in deciding an optimal care.

Case history
A 11-year old boy presented after his school teacher had
noticed unequal pupils; there was a 6-month history of
headaches and vomiting. At the initial assessment, he
had visual failure and papilloedema. Magnetic resonance imaging (MRI) scan demonstrated a suprasellar
cystic lesion breaching the floor of the third ventricle
with hydrocephalus suggestive of a craniopharyngioma.
Preoperative endocrine review elicited a history of
fatigue but no problems with growth. His appetite was
unaltered but he was drinking more than usual. On
examination, his height was C0.7 S.D. and weight C1.4
S.D.; he was prepubertal. Baseline investigation showed
that the prolactin level was normal and a-fetoprotein
and b-human chorionic gonadotrophin levels were
undetectable. Thyroid function tests were indicative of
central hypothyroidism (thyroid-stimulating hormone
0.01 mIU/l; fT4 7 pmol/l). Initial endocrine management included hydrocortisone replacement with
DOI: 10.1530/EJE-08-0400
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H Gleeson and others

additional i.v. hydrocortisone cover at the induction of
anaesthesia for neurosurgery. Neurosurgical management included the insertion of an external ventricular
drain followed by radical resection. Histology confirmed
the diagnosis of craniopharyngioma. Neurosurgery
was followed by a 6-week course of external beam
radiotherapy as there was post-operative evidence of
residual tumour.
Diabetes insipidus (DI) occurred immediately postoperatively with increased urine output and rising sodium
levels (peak serum Na 160 mmol/l). This was treated
with desmopressin (DDAVP) and increased fluid input.
After day 4, sodium levels began to fall and the patient
had a seizure on day 6 (serum Na 130 mmol/l). The initial
interpretation of the clinical picture was a syndrome
of inappropriate anti-diuretic hormone secretion
(SIADH) and fluid restriction was introduced. As serum
sodium levels continued to fall and there was concern
about volume depletion, an alternative diagnosis of
cerebral salt wasting (CSW) was considered. Management was changed to sodium and fluid replacement
and optimisation of hormone replacement therapy.
Serum sodium levels increased and the patient once
again developed polyuria and hypernatraemia, thus
signifying permanent DI.
During the early post-operative period, he was noted
to be ‘eating well, rather too well’ and ‘more aggressive’.
Anterior pituitary function testing confirmed panhypopituitarism. Ophthalmology review revealed a marked
afferent papillary defect with optic neuropathy and a
nasal visual field loss. Visual acuity was !1/60 in his
right eye and an intact visual field with reduced visual
acuity of 6/24 was observed in the left eye. This
improved after 24 months.
Psychological, behavioural and social problems were
complicating factors in management. Even in the
immediate post-operative period, he began refusing
medication and blood tests. An aggressive outburst, 8
weeks post-operatively, required acute admission in
order to provide respite for his single parent father.
During that admission, he expressed concerns that ‘he
was fat’ and ‘he wanted to kill himself ’.
During the first post-operative year, his weight
increased from 46 kg (C1.4 S.D.) to 98 kg (C3.7 S.D.;
Fig. 1). Excessive weight was beginning to cause
mobility problems and a fall resulted in a slipped right
upper femoral epiphysis; the epiphyses were pinned
bilaterally. Testosterone and growth hormone (GH)
replacement were started. Needle phobia led to poor
compliance with GH treatment; even so, growth was
unaffected with no reduction in height S.D. (last recorded
height C1.6 S.D.). During the second year, his weight
continued to increase reaching 120 kg (C4.2 S.D.).
However, over a period of 6 months, his weight reduced
to 104 kg (C3.8 S.D.; Fig. 1). The patient refused blood
tests until he became unwell and required further
admission to hospital. Investigations revealed significant dehydration with hyperglycaemia (plasma
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EUROPEAN JOURNAL OF ENDOCRINOLOGY (2008) 159

Figure 1 Patient’s weight chart indicating two time points –
occurrence of fall and slipped femoral epiphysis, and period of
sustained weight loss prior to the diagnosis of DKA secondary to
severe insulin resistance.

glucose 22 mmol/l), ketonuria and acidosis (pH 7.2;
plasma bicarbonate 7 mmol/l). Diabetic ketoacidosis
(DKA), secondary to severe insulin resistance, was
diagnosed and he was treated accordingly. He was obese
and had a family history of type 2 diabetes mellitus, and
acanthosis nigricans, insulin autoantibodies (IAA) and
glutamic acid decarboxylase (GAD) antibodies were
negative and insulin levels were high. He responded well
initially to metformin and subsequently was also started
on a thiazolidinedione and an incretin mimetic.
During his admission with DKA, the patient
developed a left hemiplegia and a subsequent cerebral
angiogram demonstrated widespread stenoses around
the Circle of Willis with a Moyamoya type appearance
(Fig. 2). He made a good recovery but subsequently had
two transient ischaemic attacks and was started on
aspirin and dipyridamole. Following the diagnosis of

Figure 2 Cerebral angiogram demonstrating widespread stenoses
of the arteries around the Circle of Willis and a moderate Moyamoya
appearance.

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2008) 159

type 2 diabetes, his weight continued to increase over
the following year from 104 kg (C3.8 S.D.) to 172 kg
(C5.5 S.D.; Fig. 1). The options for weight management
are currently being considered.

Discussion
This case demonstrates the significant morbidity that is
present at diagnosis and that can occur following
treatment with neurosurgery and radiotherapy. At
presentation, the patient had visual failure and
hypopituitarism, but hypothalamic function was essentially intact. Following radical resection of a craniopharyngioma breaching the floor of the third ventricle,
hypothalamic morbidity occurred. Psychological and
behavioural problems complicated management.
Hyperphagia resulted in uncontrolled obesity that led
to the sequelae of a slipped femoral epiphysis and severe
insulin resistance presenting as DKA. In addition, there
was the occurrence of a rarely reported late effect of
radiotherapy, cerebral artery stenoses which, in the
setting of dehydration with DKA, caused neurological
deficits. Morbid obesity, type 2 diabetes mellitus and a
high risk of stroke have a significant impact on his
quality of life and life expectancy.
The following discussion addresses the importance of
individualising initial treatment for the patient with a
craniopharyngioma and considers potential strategies
for managing hypothalamic obesity. Morbidity is
significant even at initial diagnosis in patients with a
craniopharyngioma (7–9). This may include symptoms
and signs related to raised intracranial pressure (present
in O50%), encroachment of the tumour on the optic
nerves resulting in visual failure (30–60%), hypothalamic involvement (up to 30%), endocrine manifestations such as anterior hypopituitarism (20–30%)
and DI (9–17%), and in some cases, chemical
meningitis following cyst rupture.
The location and the aggressive nature of the tumour
pose challenges in deciding what initial treatment is
optimal. The main modalities include neurosurgery and
external beam radiotherapy. There are no randomised
control studies to inform practice. Most evidence has
come from cancer registries. Mortality rates are affected
by initial treatment. For example, for patients treated
between 1966 and 1992, the 5-year progression-free
survival was 89% for patients treated with radiotherapy
and conservative surgery compared with 81% after
complete excision and 53% after partial excision (10).
The comparable figures at 10 years were 77%, 69% and
37% respectively. Mortality figures are improving; for
instance, patients diagnosed before 1980 had a 50%
survival at 5 and 10 years, whereas this rose to almost
100% when the diagnosis occurred after 1990 (11).
Neurosurgical treatment can range from an aggressive approach when the aim is complete excision
attempted in all patients to a conservative approach

Management of craniopharyngioma

S97

comprising biopsy, drainage of the cyst, chiasm
decompression and no intervention that would affect
the infundibulum or hypothalamus (6). The case for an
aggressive approach rests with the only chance of cure
and the possibility of avoiding the need for radiotherapy.
Complete excision is likely when tumours are less than
2 cm in diameter, but not so if greater than 4 cm (12,
13). Nearly half of craniopharyngiomas are greater
than 3 cm in diameter at diagnosis (12, 14). In patients
with larger tumours, who have hydrocephalus or
hypothalamic involvement and undergo radical resection, there is a high likelihood of hypothalamic
morbidity (O50%), operative mortality (2.5–10%)
and late mortality (11–28%) (15, 16). Of relevance to
the subject of this case presentation, hypothalamic
obesity is associated with the extent of the neurosurgical procedure. MRI studies indicate that when the
anatomy was left undisturbed, body mass index (BMI)
increased by C1.1 S.D.; whereas when there was a
breach of the tuber cinereum, BMI increased by C2.5
S.D; complete deficiency of the floor of the third ventricle
was associated with a 5.5 S.D. increase in BMI (17).
Neurosurgical management is now increasingly influenced by symptoms and signs at presentation and MRI
findings.
There is no consensus on the use of adjuvant
radiotherapy and its timing after neurosurgery. The
case for limited resection and adjuvant radiotherapy is
supported by evidence of adequate long-term control in
70–80% of patients. This treatment modality reduced
recurrence rates from 75–100% to 16–25%, with no
detriment in long-term morbidity or mortality (13). This
approach often avoids repeat surgery that is associated
with the high level of hypothalamic morbidity and
mortality (12, 13). However, there is concern about the
late effects of radiotherapy, which include neurocognitive and neuroendocrine disturbance, optic neuropathy
and the risk of secondary malignant neoplasms (18).
The incidence of these adverse events depends on the
age of the patient, volume of normal brain irradiated,
and dose and type of radiation. In the present case,
radiation-induced vasculopathy caused the Moyamoya
appearance on cerebral angiogram (Fig. 2). This is
potentially a serious complication of whole brain
radiotherapy in children with brain tumours (19).
However, this risk is probably insignificant when
compared with the morbidity and mortality associated
with the tumour itself, radical resection or repeat
surgery.
Careful management of salt and water balance is
essential during the immediate post-operative period.
Ninety per cent of patients develop DI post-operatively
which will remain permanent in 60–80% (8, 14). The
diagnosis of DI is relatively straightforward and
management involves a combination of judicial fluid
balance and DDAVP administration. By contrast,
establishing the cause of hyponatraemia can be
challenging, as illustrated in the present case.
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Possibilities include high urinary salt loss from severe
polyuria with DI, SIADH component of the triphasic
response, considered to be the secondary to vasopressin
neuronal necrosis that occurs 1–14 days following
neurosurgery or CSW. CSW may be a response to
plasma volume expansion as a result of DDAVP
treatment, or to SIADH itself. Alternatively, CSW may
be a primary response to over-secretion of atrial
natiuretic peptide or brain natiuretic peptide. SIADH
and CSW differ in certain characteristics. Thus, there is
evidence of volume depletion and suppressed plasma
aldosterone levels in CSW but not in SIADH. Levels of
uric acid are low in SIADH but not in CSW. Nevertheless, the clinical diagnosis between SIADH and CSW
is often not straightforward. Management involves fluid
restriction in the former, whereas salt and fluid
replacement and in some cases, administration of
fludrocortisone, are required for CSW.
Long-term endocrine follow-up includes assessment of
hypothalamic pituitary function and optimisation of
hormone replacement to maintain water balance, and
normal growth and pubertal development. Hypothalamic
symptoms can complicate management and may involve
disturbance of mood, temperature control and sleep. For
the endocrinologist, disturbances of thirst and appetite are
the most challenging aspects of management (7, 13, 14).
Hypodipsia or adipsia complicates the management of DI
and hyperphagia results in increasing levels of obesity
from damage to the ventromedial nucleus in the
hypothalamus. There are two hypotheses as to the
mechanism of obesity. One relates to disruption of central
appetite centres resulting in hyperphagia, followed by
obesity and hyperinsulinaemia. The other postulates
disinhibition of the efferent output of the vagus nerve
affecting the pancreatic b-cell thereby causing insulin
hypersecretion. This promotes partitioning of energy into
adipose tissue and hence obesity.
The management of hypothalamic obesity is challenging. There is little evidence of benefit from changes in
lifestyle. There is some evidence that pharmacotherapy
is beneficial and recent case reports suggest that
bariatric surgery may also be a therapeutic option. On
the basis that higher levels of insulin drive obesity, the
somatostatin analogue, octreotide, has been studied as a
potential agent to combat hypothalamic obesity. Positive
results were obtained in an initial study of eight patients
who lost 5 kg of weight and reduced their BMI by
2 kg/m2 after 6 months of therapy with octreotide (20).
A follow-up RCT in 18 subjects demonstrated that
patients receiving octreotide showed no change in BMI,
but weight increased by less than 2 kg when compared
with a BMI increase of 2 kg/m2 in a 9 kg increase in
weight in patients on placebo (21). Octreotide appears
to be effective at maintaining but not significantly
reducing weight. The use of octreotide in patients with
hypothalamic obesity remains experimental and the
benefit of weight maintenance has to be considered in
the context of frequent injections and side effects.
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EUROPEAN JOURNAL OF ENDOCRINOLOGY (2008) 159

Sibutramine is an appetite suppressant and has been
shown to be effective in simple obesity. A 20-week
double-blind RCT of sibutramine in 50 children, 22 with
hypothalamic obesity and 28 with simple obesity,
reported significant weight loss (22). However, the
reduction of BMI S.D. in children with hypothalamic
obesity was modest (0.3–0.4 S.D.) when compared with
children with simple obesity (0.9–1.0 S.D.).
Bariatric surgery is considered as the first-line
treatment for adults in the UK with simple obesity and
a BMI of greater than 50 kg/m2. It is also the secondline treatment for BMI greater than 40 kg/m2 or
35 kg/m2 with a comorbidity. There has been reluctance to consider bariatric surgery for patients with
hypothalamic obesity in view of its specific pathophysiology and that ongoing hyperphagia in a patient with
restricted gastric capacity could result in a greater risk
for the patient. The effect of gastric banding was studied
in four children with hypothalamic obesity whose mean
BMI S.D. at the time of surgery was C10.7 (2.7) S.D.;
mean follow-up was 2.9 (1.3) years and mean weight
loss per year was K0.7 (0.3) S.D. (23). In a single case
report of the effect of gastric bypass surgery in an
adolescent with hypothalamic obesity, the BMI had
fallen from O60 kg/m2 to 50 kg/m2 within 2.5 years of
surgery (24). Furthermore, insulin levels decreased
before and after meals; a similar effect occurred in
ghrelin levels pre-prandially. Both these publications
reported an improvement in eating behaviour. Bariatric
surgery may offer hope to patients with hyperphagia
and hypothalamic obesity.
In summary, the goal of treatment in craniopharyngioma is to relieve the raised ICP and optic nerve
compression, preserve existing hypothalamic function
and vision, provide long-term tumour control, avoid
repeat surgery and minimise neurotoxic effects from
surgery and radiotherapy. Initial treatment should be
tailored according to low- or high-risk factors as listed in
Table 1. Ongoing registration of patients in cancer
registries is required to collate long-term outcome in
order to better inform future management strategies in
craniopharyngioma. It is self-evident that management
is undertaken by a multi-disciplinary team, with the
endocrinologist playing a key role.
Table 1 Recommended management pathway for a paediatric
patient with a craniopharyngioma4
Risk factors
Good
Small tumour (%2–4 cm)

Poor

Large (retrochiasmatic) tumour
(O2–4 cm)
No hydrocephalus
Hydrocephalus
No hypothalamic symptoms
Hypothalamic symptoms
No breach third ventricle floor
Breach third ventricle floor
Consider radical resection with Consider limited resection
radiotherapy if necessary
with adjuvant radiotherapy
Recommended management

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2008) 159

Acknowledgements
H G and R A acknowledge the staff of the Department of Paediatric
Endocrinology at Royal Manchester Children’s Hospital who are
responsible for the care of the patient in this case presentation.

Disclosure
This paper forms part of a European Journal of Endocrinology supplement,
supported by Ferring Pharmaceuticals. The authors disclose: no
potential conflicting relationship with Ferring. This article was subject
to rigorous peer review before acceptance and publication.

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Received 22 May 2008
Accepted 4 September 2008

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