Familial pituitary adenoma is a rare syndrome which may present either as 
isolated lesions, or in association with other endocrine tumors, for example in 
the frame of multiple endocrine neoplasia (MEN-1) or Carney complex (CNC). The 
most frequently described forms of familial isolated pituitary adenoma (FIPA) 
are familial somatotropinomas or prolactinomas. Recently, some cases of familial 
isolated somatotropinoma have been associated with germline mutations in the 
aryl hydrocarbon receptor interacting protein (AIP) gene. The present report 
shows heterogeneous FIPA with 3 subtypes of tumor in 3 individuals of the same 
family: somatotropinoma in the proband, giant prolactinoma in a brother, and 
gonadotroph cell macroadenoma in the father. A prospective survey also suggested 
the occurrence of a silent microadenoma in the proband's sister. Clinical 
screening was performed in the 3 affected members, the 4th suspected case, and 9 
additional, asymptomatic relatives. They had no clinical evidence of associated 
endocrine lesion suggesting MEN-1 or CNC. Genetic screening for germline 
mutation of the MEN-1, the gene encoding the protein kinase A (PKA) type 1 alpha 
regulatory subunit (R1 alpha) (PRKAR1alpha) and AIP gene was negative in 2 
affected members. In conclusion, these data suggest that familial pituitary 
adenomas can occur with a heterogeneous functional pattern that is distinguished 
from MEN-1 or CNC. The absence of mutation of the recently described AIP gene 
suggests the implication of other predisposing gene(s). Collaborative, 
multicentric studies are needed to further define the location of gene(s) 
involved in heterogeneous FIPA.