Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study.
BACKGROUND
AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively.


OBJECTIVE
The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas.


METHODS
This study was an international, multicenter, retrospective case collection/database analysis.


METHODS
The study was conducted at 36 tertiary referral endocrine and clinical genetics departments.


METHODS
Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls.


RESULTS
The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy.


CONCLUSIONS
AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.
Daly
Adrian F
AF
Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium.
Tichomirowa
Maria A
MA
Petrossians
Patrick
P
Heliövaara
Elina
E
Jaffrain-Rea
Marie-Lise
ML
Barlier
Anne
A
Naves
Luciana A
LA
Ebeling
Tapani
T
Karhu
Auli
A
Raappana
Antti
A
Cazabat
Laure
L
De Menis
Ernesto
E
Montañana
Carmen Fajardo
CF
Raverot
Gerald
G
Weil
Robert J
RJ
Sane
Timo
T
Maiter
Dominique
D
Neggers
Sebastian
S
Yaneva
Maria
M
Tabarin
Antoine
A
Verrua
Elisa
E
Eloranta
Eija
E
Murat
Arnaud
A
Vierimaa
Outi
O
Salmela
Pasi I
PI
Emy
Philippe
P
Toledo
Rodrigo A
RA
Sabaté
Maria Isabel
MI
Villa
Chiara
C
Popelier
Marc
M
Salvatori
Roberto
R
Jennings
Juliet
J
Longás
Angel Ferrandez
AF
Labarta Aizpún
José Ignacio
JI
Georgitsi
Marianthi
M
Paschke
Ralf
R
Ronchi
Cristina
C
Valimaki
Matti
M
Saloranta
Carola
C
De Herder
Wouter
W
Cozzi
Renato
R
Guitelman
Mirtha
M
Magri
Flavia
F
Lagonigro
Maria Stefania
MS
Halaby
Georges
G
Corman
Vinciane
V
Hagelstein
Marie-Thérèse
MT
Vanbellinghen
Jean-François
JF
Barra
Gustavo Barcelos
GB
Gimenez-Roqueplo
Anne-Paule
AP
Cameron
Fergus J
FJ
Borson-Chazot
Françoise
F
Holdaway
Ian
I
Toledo
Sergio P A
SP
Stalla
Günter K
GK
Spada
Anna
A
Zacharieva
Sabina
S
Bertherat
Jerome
J
Brue
Thierry
T
Bours
Vincent
V
Chanson
Philippe
P
Aaltonen
Lauri A
LA
Beckers
Albert
A
D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000367:Age Factors; D018491:Dopamine Agonists / Q000627:therapeutic use; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome
D018491:Dopamine Agonists