The excess mortality in craniopharyngiomas is attributable to their size, site and the traditional surgical approach; aggressive resection predisposes to hypothalamic complications such as obesity, somnolence, thirst disorders and neurocognitive dysfunction. Recently, treatment has been modified to partial resection and radiotherapy. The role of the endocrinologist has expanded from identification and replacement of hormone deficits to include management of hypothalamic disease. Future treatment of craniopharyngioma with neo-adjuvant chemotherapy to minimise surgical resection may improve the outcomes for these patients.
Rachel K Crowley has received an unrestricted educational grant from Novo Nordisk. Christopher J Thompson has no conflicts of interest to disclose.
No funding was received for the publication of this article.
This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution,
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July 06, 2015 Published Online:
August 18, 2015
Rachel K Crowley, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. E: R.Crowley@st-vincents.ie
Craniopharyngiomas are large tumours that extend beyond the sella and suprasellar region into the hypothalamus.1 Every case series has indicated a higher mortality in craniopharyngioma than has been reported in pituitary adenoma series or in other cases of hypopituitarism. There is now a better understanding of the factors that contribute to both the morbidity and mortality associated with craniopharyngioma, which has led to a change in clinical practice and an expansion of the role of the endocrinologist.
Traditional Approach to Management of the Patient with Craniopharyngioma
Although the histology is described as benign, craniopharyngiomas form micropapillary extensions into surrounding hypothalamic tissue, which promote a gliotic reaction.2 Surgical resection of these lesions is difficult because of their adherence to surrounding hypothalamic structures. The traditional surgical approach was to attempt gross total resection (GTR), often via a frontal or pterional craniotomy. Aggressive surgery was associated with high rates of panhypopituitarism and diabetes insipidus, morbid obesity, disorders of appetite and thirst, somnolence, poikilothermia and a range of neurocognitive deficits.3–8 Despite attempts at surgical clearance, rates of tumour recurrence were as high as 40 %.3
Traditional methods of management of craniopharyngioma are also associated with high standardised mortality, despite adequate replacement of pituitary hormone deficiencies.3,9,10 Routine management has changed to address some of the morbidities associated with craniopharyngioma.
In the last 10 years there has been a change in surgical approach to a modified transsphenoidal resection in parallel with radiotherapy and radiosurgery. It is not possible to conduct large-scale trials for this rare tumour, but published data indicate that less-aggressive surgery is not complicated by an increase in tumour recurrence rates.11,12 Hypothalamus-sparing surgery in children with craniopharyngioma results in lower rates of obesity than in children who have undergone a traditional surgical approach.11
Analysis of large pituitary disease registers has revealed that patients with craniopharyngioma differ from other hypopituitary patient groups in the rates of hormone deficiency and response to replacement therapy. Data show that they have higher rates of pre-receptor activation of cortisone to cortisol by the enzyme 11βHSD1.13 There may be less benefit from growth hormone (GH) replacement therapy in reduction of visceral adiposity and improved lipid profile.14 Although GH replacement does not appear to reduce the mortality associated with craniopharyngioma, GH therapy is safe for these patients and does not lead to tumour recurrence.15 Craniopharyngioma is also associated with higher rates of diabetes insipidus that may be complicated by adipsia or polydipsia.16 It is unclear whether modification of hormone replacement therapy will reduce the morbidity and mortality associated with craniopharyngioma; however, the recognition of the unique abnormalities seen in craniopharyngioma patients does prompt the need for further research into accurate hormone replacement in this cohort.
1. Karavitaki N, Cudlip S, Adams CB, Wass JA,
Craniopharyngiomas, Endocr Rev, 2006;27:371–97.
2. Kawamata T, Kubo O, Hori T, Histological findings at the
boundary of craniopharyngiomas, Brain Tumor Pathol,
3. Crowley R, Hamnvik O, O’Sullivan E, et al., Morbidity and
Mortality in Craniopharyngioma Patients after Surgery,
Clin Endocrinol (Oxf), 2010;73:516–21.
4. Crowley RK, Woods C, Fleming M, et al., Somnolence in adult
craniopharyngioma patients is a common, heterogeneous
condition that is potentially treatable, Clin Endocrinol (Oxf),
5. Karavitaki N, Brufani C, Warner JT, et al., Craniopharyngiomas
in children and adults: systematic analysis of 121 cases
with long-term follow-up, Clin Endocrinol (Oxf),
6. Daubenbuchel AM, Hoffmann A, Gebhardt U, et al.,
Hydrocephalus and hypothalamic involvement in pediatric
patients with craniopharyngioma or cysts of rathke’s
pouch: impact on long-term prognosis, Eur J Endocrinol,
7. Honegger J, Barocka A, Sadri B, Fahlbusch R,
Neuropsychological results of craniopharyngioma surgery
in adults: a prospective study, Surg Neurol, 1998;50:19–28;
8. Fjalldal S, Holmer H, Rylander L, et al., Hypothalamic
involvement predicts cognitive performance and psychosocial
health in long-term survivors of childhood craniopharyngioma,
J Clin Endocrinol Metab, 2013;98:3253–3262.
9. Bulow B, Attewell R, Hagmar L, et al., Postoperative prognosis
in craniopharyngioma with respect to cardiovascular
mortality, survival, and tumor recurrence, J Clin Endocrinol
10. Olsson DS, Andersson E, Bryngelsson IL, et al., Excess
mortality and morbidity in patients with craniopharyngioma,
especially in patients with childhood onset: a populationbased
study in Sweden, J Clin Endocrinol Metab,
11. Elowe-Gruau E, Beltrand J, Brauner R, et al., Childhood
craniopharyngioma: hypothalamus-sparing surgery
decreases the risk of obesity, J Clin Endocrinol Metab,
12. Hoffmann A, Warmth-Metz M, Gebhardt U, et al., Childhood
craniopharyngioma - changes of treatment strategies in
the trials KRANIOPHARYNGEOM 2000/2007, Klin Padiatr,
13. Tiosano D, Eisentein I, Militianu D, et al.,11 beta-Hydroxysteroid
dehydrogenase activity in hypothalamic obesity, J Clin
Endocrinol Metab, 2003;88:379–84.
14. Verhelst J, Kendall-Taylor P, Erfurth EM, et al., Baseline
characteristics and response to 2 years of growth hormone
(GH) replacement of hypopituitary patients with GH deficiency
due to adult-onset craniopharyngioma in comparison
with patients with nonfunctioning pituitary adenoma: data
from KIMS (Pfizer International Metabolic Database), J Clin
Endocrinol Metab, 2005;90:4636–43.
15. Karavitaki N, Warner JT, Marland A, et al., GH replacement
does not increase the risk of recurrence in patients with
craniopharyngioma, Clin Endocrinol (Oxf), 2006;64:556–60.
16. Crowley RK, Sherlock M, Agha A, et al., Clinical insights
into adipsic diabetes insipidus: a large case series, Clin
Endocrinol (Oxf), 2007;66:475–82.
17. Bretault M, Boillot A, Muzard L, et al., Clinical review: Bariatric
surgery following treatment for craniopharyngioma: a
systematic review and individual-level data meta-analysis,
J Clin Endocrinol Metab, 2013;98:2239–46.
18. Zoicas F, Droste M, Mayr B, Buchfelder M, Schofl C, GLP-1
analogues as a new treatment option for hypothalamic
obesity in adults: report of nine cases, Eur J Endocrinol,
19. Hamilton JK, Conwell LS, Syme C, et al., Hypothalamic obesity
following craniopharyngioma surgery: Results of a pilot trial
of combined diazoxide and metformin therapy, Int J Pediatr
20. Muller HL, Handwerker G, Gebhardt U, et al.,
Melatonin treatment in obese patients with childhood
craniopharyngioma and increased daytime sleepiness,
Cancer Causes Control, 2006;17:583–9.
21. Brastianos PK, Taylor-Weiner A, Manley PE, et al., Exome
sequencing identifies BRAF mutations in papillary
craniopharyngiomas, Nat Genet, 2014;46:161–5.
22. Aylwin SJ, Bodi I, Beaney R, Pronounced response of
papillary craniopharyngioma to treatment with vemurafenib,
a BRAF inhibitor, Pituitary, 2015 [Epub ahead of print].