Objective: The major part of craniopharyngioma (CP) morbidity is the tumor and/or treatment-related damage, which results in impaired function of the hypothalamic-pituitary axes and metabolic derangements. The aim of the study was to analyze the prevalence of long-term endocrine and metabolic comorbidities in a national cohort of CP patients based on the age at diagnosis and histology criteria. Design: A retrospective-prospective longitudinal cohort analysis. Methods: Forty-six patients with CP treated from 1979 onwards (19 with childhood-onset disease) in a single university institution were included in our study. Median follow-up from presentation was 12.8 years (interquartile range: 8.3–22.2 years) and comparable between age-at-diagnosis and histological subtype groups. Data on tumor histology were extracted from patients’ records and re-evaluated if tissue samples were available (n = 32). Results: Childhood-onset patients presented more frequently with headache, and adult-onset with visual impairment. Prevalence of at least one pituitary axis affected increased from 54% at presentation to 100% at follow-up in childhood-onset and from 41 to 93% in adult-onset CP. Growth hormone deficiency, central diabetes insipidus, and panhypopituitarism were more prevalent in childhood-onset adamantinomatous CP (aCP) and least prevalent in adult-onset papillary CP (pCP). At follow-up, metabolic syndrome (MetS) was diagnosed in 80% of childhood-onset and 68% of adult-onset patients (p = 0.411). In the latter group, it tended to be more frequent in the aCP than pCP subtype (80 vs. 50%, p = 0.110). Conclusions: Long-term endocrine and metabolic complications are very frequent in childhood- and adult-onset CP patients of both histological subtypes. The prevalence of MetS was higher compared to the largest cohort previously reported.

1.
Nielsen
EH
,
Feldt-Rasmussen
U
,
Poulsgaard
L
,
Kristensen
LO
,
Astrup
J
,
Jørgensen
JO
, et al.
.
Incidence of craniopharyngioma in Denmark (n = 189) and estimated world incidence of craniopharyngioma in children and adults
.
J Neurooncol
.
2011
Sep
;
104
(
3
):
755
63
.
[PubMed]
0167-594X
2.
Bunin
GR
,
Surawicz
TS
,
Witman
PA
,
Preston-Martin
S
,
Davis
F
,
Bruner
JM
.
The descriptive epidemiology of craniopharyngioma
.
J Neurosurg
.
1998
Oct
;
89
(
4
):
547
51
.
[PubMed]
0022-3085
3.
Müller
HL
.
Craniopharyngioma and hypothalamic injury: latest insights into consequent eating disorders and obesity
.
Curr Opin Endocrinol Diabetes Obes
.
2016
Feb
;
23
(
1
):
81
9
.
[PubMed]
1752-296X
4.
Müller
HL
,
Gebhardt
U
,
Teske
C
,
Faldum
A
,
Zwiener
I
,
Warmuth-Metz
M
, et al.;
Study Committee of KRANIOPHARYNGEOM 2000
.
Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up
.
Eur J Endocrinol
.
2011
Jul
;
165
(
1
):
17
24
.
[PubMed]
0804-4643
5.
Jensterle
M
,
Jazbinsek
S
,
Bosnjak
R
,
Popovic
M
,
Zaletel
LZ
,
Vesnaver
TV
, et al.
.
Advances in the management of craniopharyngioma in children and adults
.
Radiol Oncol
.
2019
Oct
;
53
(
4
):
388
96
.
[PubMed]
1318-2099
6.
Wijnen
M
,
Olsson
DS
,
van den Heuvel-Eibrink
MM
,
Hammarstrand
C
,
Janssen
JA
,
van der Lely
AJ
, et al.
.
The metabolic syndrome and its components in 178 patients treated for craniopharyngioma after 16 years of follow-up
.
Eur J Endocrinol
.
2018
Jan
;
178
(
1
):
11
22
.
[PubMed]
0804-4643
7.
Wijnen
M
,
van den Heuvel-Eibrink
MM
,
Janssen
JA
,
Catsman-Berrevoets
CE
,
Michiels
EM
,
van Veelen-Vincent
MC
, et al.
.
Very long-term sequelae of craniopharyngioma
.
Eur J Endocrinol
.
2017
Jun
;
176
(
6
):
755
67
.
[PubMed]
0804-4643
8.
Olsson
DS
,
Andersson
E
,
Bryngelsson
IL
,
Nilsson
AG
,
Johannsson
G
.
Excess mortality and morbidity in patients with craniopharyngioma, especially in patients with childhood onset: a population-based study in Sweden
.
J Clin Endocrinol Metab
.
2015
Feb
;
100
(
2
):
467
74
.
[PubMed]
0021-972X
9.
Tomlinson
JW
,
Holden
N
,
Hills
RK
,
Wheatley
K
,
Clayton
RN
,
Bates
AS
, et al.;
West Midlands Prospective Hypopituitary Study Group
.
Association between premature mortality and hypopituitarism
.
Lancet
.
2001
Feb
;
357
(
9254
):
425
31
.
[PubMed]
0140-6736
10.
Sterkenburg
AS
,
Hoffmann
A
,
Gebhardt
U
,
Warmuth-Metz
M
,
Daubenbüchel
AM
,
Müller
HL
.
Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes
.
Neuro-oncol
.
2015
Jul
;
17
(
7
):
1029
38
.
[PubMed]
1522-8517
11.
Pascual
JM
,
Prieto
R
,
Rosdolsky
M
,
Strauss
S
,
Castro-Dufourny
I
,
Hofecker
V
, et al.
.
Cystic tumors of the pituitary infundibulum: seminal autopsy specimens (1899 to 1904) that allowed clinical-pathological craniopharyngioma characterization
.
Pituitary
.
2018
Aug
;
21
(
4
):
393
405
.
[PubMed]
1386-341X
12.
Müller
HL
.
Hypothalamic involvement in craniopharyngioma-Implications for surgical, radiooncological, and molecularly targeted treatment strategies
.
Pediatr Blood Cancer
.
2018
May
;
65
(
5
):
e26936
.
[PubMed]
1545-5009
13.
Lustig
RH
,
Post
SR
,
Srivannaboon
K
,
Rose
SR
,
Danish
RK
,
Burghen
GA
, et al.
.
Risk factors for the development of obesity in children surviving brain tumors
.
J Clin Endocrinol Metab
.
2003
Feb
;
88
(
2
):
611
6
.
[PubMed]
0021-972X
14.
Holmer
H
,
Ekman
B
,
Björk
J
,
Nordstöm
CH
,
Popovic
V
,
Siversson
A
, et al.
.
Hypothalamic involvement predicts cardiovascular risk in adults with childhood onset craniopharyngioma on long-term GH therapy
.
Eur J Endocrinol
.
2009
Nov
;
161
(
5
):
671
9
.
[PubMed]
0804-4643
15.
Goschzik
T
,
Gessi
M
,
Dreschmann
V
,
Gebhardt
U
,
Wang
L
,
Yamaguchi
S
, et al.
.
Genomic alterations of adamantinomatous and papillary craniopharyngioma
.
J Neuropathol Exp Neurol
.
2017
Feb
;
76
(
2
):
126
34
.
[PubMed]
0022-3069
16.
Rostami
E
,
Witt Nyström
P
,
Libard
S
,
Wikström
J
,
Casar-Borota
O
,
Gudjonsson
O
.
Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant-targeted therapy
.
Acta Neurochir (Wien)
.
2017
Nov
;
159
(
11
):
2217
21
.
[PubMed]
0001-6268
17.
Roque
A
,
Odia
Y
.
BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors
.
CNS Oncol
.
2017
Apr
;
6
(
2
):
95
9
.
[PubMed]
2045-0907
18.
Himes
BT
,
Ruff
MW
,
Van Gompel
JJ
,
Park
SS
,
Galanis
E
,
Kaufmann
TJ
, et al.
.
Recurrent papillary craniopharyngioma with BRAF V600E mutation treated with dabrafenib: case report
.
J Neurosurg
.
2018
Apr
;
130
(
4
):
1
5
.
[PubMed]
1933-0693
19.
Aylwin
SJ
,
Bodi
I
,
Beaney
R
.
Pronounced response of papillary craniopharyngioma to treatment with vemurafenib, a BRAF inhibitor
.
Pituitary
.
2016
Oct
;
19
(
5
):
544
6
.
[PubMed]
1386-341X
20.
Brastianos
PK
,
Taylor-Weiner
A
,
Manley
PE
,
Jones
RT
,
Dias-Santagata
D
,
Thorner
AR
, et al.
.
Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas
.
Nat Genet
.
2014
Feb
;
46
(
2
):
161
5
.
[PubMed]
1061-4036
21.
Müller
HL
,
Martinez-Barbera
JP
. Adamantinomatous Craniopharyngioma: Genomics, Radiologic Findings, Clinical, and Prognosis.
Pituitary Disorders of Childhood, Contemporary Endocrinology
.
Cham
:
Humana Press
;
2019
. pp.
41
70
.
22.
Prabhu
VC
,
Brown
HG
.
The pathogenesis of craniopharyngiomas
.
Childs Nerv Syst
.
2005
Aug
;
21
(
8-9
):
622
7
.
[PubMed]
0256-7040
23.
Cole
TJ
,
Freeman
JV
,
Preece
MA
.
British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood
.
Stat Med
.
1998
Feb
;
17
(
4
):
407
29
.
[PubMed]
0277-6715
24.
Zimmet
P
,
Alberti
KG
,
Kaufman
F
,
Tajima
N
,
Silink
M
,
Arslanian
S
, et al.;
IDF Consensus Group
.
The metabolic syndrome in children and adolescents - an IDF consensus report
.
Pediatr Diabetes
.
2007
Oct
;
8
(
5
):
299
306
.
[PubMed]
1399-543X
25.
Zeitler
P
,
Arslanian
S
,
Fu
J
,
Pinhas-Hamiel
O
,
Reinehr
T
,
Tandon
N
, et al.
.
ISPAD Clinical Practice Consensus Guidelines 2018: Type 2 diabetes mellitus in youth
.
Pediatr Diabetes
.
2018
Oct
;
19
Suppl 27
:
28
46
.
[PubMed]
1399-543X
26.
Punthakee
Z
,
Goldenberg
R
,
Katz
P
;
Diabetes Canada Clinical Practice Guidelines Expert Committee
.
Definition, Classification and diagnosis of diabetes, prediabetes and metabolic syndrome
.
Can J Diabetes
.
2018
Apr
;
42
Suppl 1
:
S10
5
.
[PubMed]
1499-2671
27.
Puget
S
,
Garnett
M
,
Wray
A
,
Grill
J
,
Habrand
JL
,
Bodaert
N
, et al.
.
Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement
.
J Neurosurg
.
2007
Jan
;
106
(
1
Suppl
):
3
12
.
[PubMed]
0022-3085
28.
Templ
M
.
Statistical Disclosure Control for Microdata Using the R-Package sdcMicro
.
Trans Data Priv
.
2008
;
1
(
2
):
67
85
.1888-5063
29.
Bosnjak
R
,
Benedicic
M
,
Vittori
A
.
Early outcome in endoscopic extended endonasal approach for removal of supradiaphragmatic craniopharyngiomas: a case series and a comprehensive review
.
Radiol Oncol
.
2013
Jul
;
47
(
3
):
266
79
.
[PubMed]
1318-2099
30.
Brastianos
PK
,
Shankar
GM
,
Gill
CM
,
Taylor-Weiner
A
,
Nayyar
N
,
Panka
DJ
, et al.
.
Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy
.
J Natl Cancer Inst
.
2015
Oct
;
108
(
2
):
djv310
.
[PubMed]
0027-8874
31.
Mortini
P
,
Losa
M
,
Pozzobon
G
,
Barzaghi
R
,
Riva
M
,
Acerno
S
, et al.
.
Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series
.
J Neurosurg
.
2011
May
;
114
(
5
):
1350
9
.
[PubMed]
0022-3085
32.
Crotty
TB
,
Scheithauer
BW
,
Young
WF
Jr
,
Davis
DH
,
Shaw
EG
,
Miller
GM
, et al.
.
Papillary craniopharyngioma: a clinicopathological study of 48 cases
.
J Neurosurg
.
1995
Aug
;
83
(
2
):
206
14
.
[PubMed]
0022-3085
33.
Müller
HL
.
Childhood craniopharyngioma
.
Pituitary
.
2013
Mar
;
16
(
1
):
56
67
.
[PubMed]
1386-341X
34.
Hoffmann
A
,
Boekhoff
S
,
Gebhardt
U
,
Sterkenburg
AS
,
Daubenbüchel
AM
,
Eveslage
M
, et al.
.
History before diagnosis in childhood craniopharyngioma: associations with initial presentation and long-term prognosis
.
Eur J Endocrinol
.
2015
Dec
;
173
(
6
):
853
62
.
[PubMed]
0804-4643
35.
Borrill
R
,
Cheesman
E
,
Stivaros
S
,
Kamaly-Asl
ID
,
Gnanalingham
K
,
Kilday
JP
.
Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: a case report and review of the literature
.
Childs Nerv Syst
.
2019
Jan
;
35
(
1
):
169
73
.
[PubMed]
0256-7040
36.
Zoicas
F
,
Schöfl
C
.
Craniopharyngioma in adults
.
Front Endocrinol (Lausanne)
.
2012
Mar
;
3
:
46
.
[PubMed]
1664-2392
37.
Nomura
S
,
Aihara
Y
,
Amano
K
,
Eguchi
S
,
Chiba
K
,
Komori
T
, et al.
.
A Rare Case of Malignant Craniopharyngioma Reactive to Adjunctive Stereotactic Radiotherapy and Chemotherapy: Case Report and Literature Review
.
World Neurosurg
.
2018
Sep
;
117
:
332
8
.
[PubMed]
1878-8750
38.
Gautier
A
,
Godbout
A
,
Grosheny
C
,
Tejedor
I
,
Coudert
M
,
Courtillot
C
, et al.;
Craniopharyngioma Study Group
.
Markers of recurrence and long-term morbidity in craniopharyngioma: a systematic analysis of 171 patients
.
J Clin Endocrinol Metab
.
2012
Apr
;
97
(
4
):
1258
67
.
[PubMed]
0021-972X
39.
Karavitaki
N
,
Brufani
C
,
Warner
JT
,
Adams
CB
,
Richards
P
,
Ansorge
O
, et al.
.
Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up
.
Clin Endocrinol (Oxf)
.
2005
Apr
;
62
(
4
):
397
409
.
[PubMed]
0300-0664
40.
Kendall-Taylor
P
,
Jönsson
PJ
,
Abs
R
,
Erfurth
EM
,
Koltowska-Häggström
M
,
Price
DA
, et al.
.
The clinical, metabolic and endocrine features and the quality of life in adults with childhood-onset craniopharyngioma compared with adult-onset craniopharyngioma
.
Eur J Endocrinol
.
2005
Apr
;
152
(
4
):
557
67
.
[PubMed]
0804-4643
41.
Feng
Y
,
Ni
M
,
Wang
YG
,
Zhong
LY
.
Comparison of neuroendocrine dysfunction in patients with adamantinomatous and papillary craniopharyngiomas
.
Exp Ther Med
.
2019
Jan
;
17
(
1
):
51
6
.
[PubMed]
1792-0981
42.
Lawson
SA
,
Horne
VE
,
Golekoh
MC
,
Hornung
L
,
Burns
KC
,
Fouladi
M
, et al.
.
Hypothalamic-pituitary function following childhood brain tumors: analysis of prospective annual endocrine screening
.
Pediatr Blood Cancer
.
2019
May
;
66
(
5
):
e27631
.
[PubMed]
1545-5009
43.
Pekmezci
M
,
Louie
J
,
Gupta
N
,
Bloomer
MM
,
Tihan
T
.
Clinicopathological characteristics of adamantinomatous and papillary craniopharyngiomas: university of California, San Francisco experience 1985-2005
.
Neurosurgery
.
2010
Nov
;
67
(
5
):
1341
9
.
[PubMed]
0148-396X
44.
Nie
J
,
Huang
GL
,
Deng
SZ
,
Bao
Y
,
Liu
YW
,
Feng
ZP
, et al.
.
The purine receptor P2X7R regulates the release of pro-inflammatory cytokines in human craniopharyngioma
.
Endocr Relat Cancer
.
2017
Jun
;
24
(
6
):
287
96
.
[PubMed]
1351-0088
45.
Zhou
J
,
Zhang
C
,
Pan
J
,
Chen
L
,
Qi
ST
.
Interleukin‑6 induces an epithelial‑mesenchymal transition phenotype in human adamantinomatous craniopharyngioma cells and promotes tumor cell migration
.
Mol Med Rep
.
2017
Jun
;
15
(
6
):
4123
31
.
[PubMed]
1791-2997
46.
Mao
J
,
Qiu
B
,
Mei
F
,
Liu
F
,
Feng
Z
,
Fan
J
, et al.
.
Interleukin-1α leads to growth hormone deficiency in adamantinomatous craniopharyngioma by targeting pericytes: implication in pituitary fibrosis
.
Metabolism
.
2019
Dec
;
101
:
153998
.
[PubMed]
0026-0495
47.
Lustig
RH
.
Hypothalamic obesity: the sixth cranial endocrinopathy
.
Endocrinologist
.
2002
;
12
(
3
):
210
7
. 1051-2144
48.
Roth
CL
,
Eslamy
H
,
Werny
D
,
Elfers
C
,
Shaffer
ML
,
Pihoker
C
, et al.
.
Semiquantitative analysis of hypothalamic damage on MRI predicts risk for hypothalamic obesity
.
Obesity (Silver Spring)
.
2015
Jun
;
23
(
6
):
1226
33
.
[PubMed]
1930-7381
49.
Holmer
H
,
Pozarek
G
,
Wirfält
E
,
Popovic
V
,
Ekman
B
,
Björk
J
, et al.
.
Reduced energy expenditure and impaired feeding-related signals but not high energy intake reinforces hypothalamic obesity in adults with childhood onset craniopharyngioma
.
J Clin Endocrinol Metab
.
2010
Dec
;
95
(
12
):
5395
402
.
[PubMed]
0021-972X
50.
Daubenbüchel
AM
,
Hoffmann
A
,
Gebhardt
U
,
Warmuth-Metz
M
,
Sterkenburg
AS
,
Müller
HL
.
Hydrocephalus and hypothalamic involvement in pediatric patients with craniopharyngioma or cysts of Rathke’s pouch: impact on long-term prognosis
.
Eur J Endocrinol
.
2015
May
;
172
(
5
):
561
9
.
[PubMed]
0804-4643
51.
Duff
J
,
Meyer
FB
,
Ilstrup
DM
,
Laws
ER
Jr
,
Schleck
CD
,
Scheithauer
BW
.
Long-term outcomes for surgically resected craniopharyngiomas
.
Neurosurgery
.
2000
Feb
;
46
(
2
):
291
302
.
[PubMed]
0148-396X
52.
van Iersel
L
,
Meijneke
RW
,
Schouten-van Meeteren
AY
,
Reneman
L
,
de Win
MM
,
van Trotsenburg
AS
, et al.
.
The development of hypothalamic obesity in craniopharyngioma patients: A risk factor analysis in a well-defined cohort
.
Pediatr Blood Cancer
.
2018
May
;
65
(
5
):
e26911
.
[PubMed]
1545-5009
53.
Cornier
MA
,
Dabelea
D
,
Hernandez
TL
,
Lindstrom
RC
,
Steig
AJ
,
Stob
NR
, et al.
.
The metabolic syndrome
.
Endocr Rev
.
2008
Dec
;
29
(
7
):
777
822
.
[PubMed]
0163-769X
54.
Profka
E
,
Giavoli
C
,
Bergamaschi
S
,
Ferrante
E
,
Malchiodi
E
,
Sala
E
, et al.
.
Analysis of short- and long-term metabolic effects of growth hormone replacement therapy in adult patients with craniopharyngioma and non-functioning pituitary adenoma
.
J Endocrinol Invest
.
2015
Apr
;
38
(
4
):
413
20
.
[PubMed]
0391-4097
You do not currently have access to this content.