Clinical characterization of familial isolated pituitary adenomas.
BACKGROUND
Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC).


OBJECTIVE
Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA).


METHODS
We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands.


RESULTS
Sixty-four FIPA families including 138 affected individuals were identified [55 prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH-secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree relationships predominated (75.6%) among affected individuals. A single tumor phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation of multigenerational families. Macroadenomas were more frequent in heterogeneous vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous families were larger and had more frequent suprasellar extension (P = 0.004) than sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma cases and within heterogeneous FIPA families; isolated familial somatotropinoma cases represented 18% of FIPA cases and were younger at diagnosis than patients with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P = 0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases.


CONCLUSIONS
Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.
Daly
A F
AF
Department of Endocrinology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart Tilman, 4000 Liège, Belgium.
Jaffrain-Rea
M-L
ML
Ciccarelli
A
A
Valdes-Socin
H
H
Rohmer
V
V
Tamburrano
G
G
Borson-Chazot
C
C
Estour
B
B
Ciccarelli
E
E
Brue
T
T
Ferolla
P
P
Emy
P
P
Colao
A
A
De Menis
E
E
Lecomte
P
P
Penfornis
F
F
Delemer
B
B
Bertherat
J
J
Wémeau
J L
JL
De Herder
W
W
Archambeaud
F
F
Stevenaert
A
A
Calender
A
A
Murat
A
A
Cavagnini
F
F
Beckers
A
A
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D005260:Female; D006065:Gonadotropins, Pituitary / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010908:Pituitary Hormones, Anterior / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015175:Prolactinoma / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D006065:Gonadotropins, Pituitary; C517834:PRKAR1A protein, human; D010908:Pituitary Hormones, Anterior; D000324:Adrenocorticotropic Hormone; D017868:Cyclic AMP-Dependent Protein Kinases