Familial isolated pituitary adenomas and AIP gene mutations

Inherited genetic conditions associated with pituitary tumours are rare and include multiple endocrine neoplasia type 1 (MEN1) and Carney complex. Such hereditary pituitary adenomas are of great interest genetically and clinically as they can permit precocious diagnosis of tumors in carriers of genetic mutations, and as clinical evidence suggests that these tumors may be more aggressive than general sporadic equivalents. In 2000 the first series of 27 patients with a new hereditary tumor condition, familial isolated pituitary adenomas (FIPA) that is unrelated to other syndromes has been described in Liège. In 2006, Vierimaa and coworkers described AIP as a gene assosiated with predisposition to pituitary adenomas in familial setting. AIP mutations were found in 20.4% of FIPA families (36.1% in families homogeneous for GH secretion). In FIPA families, adenomas usually occur earlier and are more aggressive than in sporadic cases. We have also showed that patients with AIP mutations in the FIPA setting are predominantly male and have larger and more aggressive tumors that occur more than 10 years before those without AIP mutations. Responses to treatment may not be as favourable in AIP mutated patients. All types of pituitary adenomas can occur in FIPA cases regardless their AIP status. However in AIP mutated patients, GH or GH + PRL secreting adenomas are predominant. In a study of 76 young patients with Cushings disease, only one had an AIP mutation. In another study of more than 150 supposedly sporadic adenomas in young patients (less than 30 years) with macro-adenomas more than 15 % had AIP mutations (all of which were GH or PRL secreting). FIPA is not uncommon (approximately 2% of all pituitary adenomas). AIP mutation screening should be considered in all patients with FIPA and in young patients suffering from aggressive GH or PRL secreting adenomas.