Update on familial pituitary tumors: from multiple endocrine neoplasia type I to familial isolated pituitary adenomas
Inherited genetic conditions associated with pituitary tumours include multiple endocrine neoplasia type I (MEN-I) and Carney complex. Pituitary tumours that occur in the setting of MEN-I and Carney complex have specific clinical characteristics in terms of severity, which can help to guide clinical management. In 2000, we reported the first series of 27 patients with FIPA. Later on, the number of FIPA families has increased to more than 130 today.
In 2006, Vierimaa and coworkers found inactivating mutations in the gene encoding AIP in familial pituitary adenoma patients. AIP mutations were found in 15% of FIPA families (50% in families homogeneous for GH secretion).
In FIPA families, adenomas usually occur earlier and are more aggressive than in sporadic cases. Also, FIPA patients who bear an AIP mutation have more aggressive tumours that occur earlier than patients without AIP mutations. Responses to treatment may not be as favourable in AIP mutated patients. The FIPA cohort includes all types of adenomas, as can occur in AIP mutated FIPA cases. 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 (<30 years) with macro-adenomas more than 15% had AIP mutations (all of which were GH or PRL secreting).
FIPA is not uncommon (more than 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.