BACKGROUND: The paradox of pituitary tumours is that persistent growth is so 
atypical. By definition, all pituitary microadenomas regain complete trophic 
stability after an initial period of deregulated growth. Unlike tumours in many 
other organ systems, concern about significant growth of macroadenoma remnants 
after debulking is minimal. Despite reports of a relatively high prevalence of 
aneuploidy and clonal skewing in these tumours, prolonged efforts to implicate 
classical proto-oncogene activation and tumour suppressor mutations have been of 
limited success. No histological or molecular markers reliably predict 
behaviour. To date, the number of molecular genetic factors unequivocally linked 
to pituitary tumours can be counted on the fingers of one hand: (1) GNAS1 
activation in acromegaly; (2) the MENIN and p27Kip1 (CDKN1B) mutations 
associated with multiple endocrine neoplasia type 1; (3) mutations of PRKA1RA 
with loss of 17q22-24 in Carney complex, and (4) aryl hydrocarbon receptor 
interacting protein gene mutations in 15% of familial isolated pituitary 
adenomas and 50% of familial isolated acromegaly. Together, these account for 
only a small proportion (<5%) of sporadic pituitary macroadenomas.
CONCLUSION: In most instances, we still do not know what causes quantitative 
aberrations in trophic behaviour.