Genetic changes in anterior pituitary tumours could be divided to germline and somatic changes. Regarding hereditary cases, while relatively rare, they are increasingly recognised. They occur in either isolated form [familial isolated pituitary adenoma (FIPA) due to germline mutations in the AIP gene or GPR101 duplications] or as part of a syndromic disease, such as multiple endocrine neoplasia (MEN) type 1 or 4, Carney complex, McCune–Albright syndrome, phaeochromocytoma/paraganglioma with pituitary adenoma, DICER1 or Lynch syndrome.

Pituitary tumours caused by a germline genetic abnormality are usually young-onset, more aggressive and resistant to different treatment modalities.

AIP-mutation positive FIPA cases are mainly growth-hormone or prolactin secreting, large, invasive pituitary tumours with an early age of onset. These tumours need to be reoperated more often and respond less well to somatostatin receptor ligand therapy.

Duplication of GPR101 gene causes infant-onset gigantism (named X-linked acrogigantism). Radical surgical approach is often needed in these cases, followed by pegvisomant therapy, while first generation somatostatin receptor ligands and radiotherapy usually does not lead to disease control.

MEN1 is characterized by pituitary (most often prolactin-producing), parathyroid and pancreas tumours accompanied by non-endocrine neoplasms. MEN4 shows a MEN1-like phenotype without the presence of a MEN1 gene mutation, but with germline alterations in the CDKN1B gene. The treatment strategy in MEN1and MEN4-related pituitary tumours does not differ from sporadic pituitary tumours.

Phaeochromocytoma/paraganglioma might be associated with pituitary tumours (3Pa syndrome) due to mutations in the SDHx or MAX gene. SDHx-related pituitary tumours are usually large, aggressive tumours, even with the possibility of pituitary carcinoma.

Somatic genetic changes are most often seen in somatotroph tumours (GNAS) and corticotroph tumours (USP8), both represents cases with the milder end of the spectrum of the disease. More recently ATRX mutations have been described in some aggressive cases (most often corticotrophinomas).

In conclusion, pituitary tumours due to germline changes are more challenging to treat. On the other hand, identification of the genetic background allows screening for tumours resulting in earlier diagnosis, and therefore better outcome.