What causes Pituitary Adenoma (Pituitary tumor)?

From the Guidelines

Pituitary adenomas are primarily caused by genetic mutations, with several genes identified in association with these tumors, including AIP, GPR101, and MEN1, as highlighted in a 2024 consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence 1. The exact trigger for these mutations is often unknown, but they can occur as isolated pituitary adenomas or as part of a syndromic disease. Several factors may contribute to their development, including:

• Inherited genetic conditions like Multiple Endocrine Neoplasia type 1 (MEN1) and familial isolated pituitary adenoma (FIPA)
• Certain gene mutations, particularly in the AIP gene, which have been identified in some cases, with AIP mutations occurring in 29% of patients with gigantism 1
• Environmental factors and hormonal imbalances, though research in this area is ongoing Most pituitary adenomas occur sporadically without a clear hereditary link, but genetic assessment is recommended for all children and adolescents with a pituitary adenoma to inform management and family surveillance, as stated in the 2024 guideline 1. While these tumors are typically benign, they can cause problems by either overproducing hormones or growing large enough to compress surrounding brain structures, leading to various symptoms depending on the type and size of the adenoma. Key genetic abnormalities associated with pituitary adenomas include:
• AIP mutations, which are the most common genetic cause of gigantism, occurring in 29% of patients 1
• GPR101 duplications, which occur in 10% of patients with GH-secreting adenoma 1
• MEN1 mutations, which occur in 1% of patients with GH-secreting adenoma 1 Regular medical monitoring is important for those with known risk factors or family history of these tumors, with genetic testing and clinical screening recommended for family members of patients with identified genetic mutations 1.

From the Research

Causes of Pituitary Adenoma

• The exact cause of pituitary adenoma is not fully understood, but it is believed to be related to genetic mutations and altered gene expression 2, 3.
• The majority of pituitary adenomas have a sporadic origin, with recognized genetic mutations seldom being found 2.
• However, some pituitary adenomas can be caused by genetic syndromes such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex 2, 4.
• Familial cases of pituitary adenomas represent 5% of all pituitary tumors, and genetic defects in the aryl hydrocarbon receptor interacting protein (AIP) gene have been identified in some of these cases 2, 3.
• Somatic mutations, epigenetic changes, and abnormal microRNAs have also been detected in pituitary adenomas 3.

Genetic Factors

• Germline mutations in the MEN1 gene can cause MEN1, a rare autosomal-dominant tumor disorder characterized by the development of pituitary tumors and other endocrine neoplasms 4.
• Mutations in the AIP gene have been identified in some cases of familial isolated pituitary adenoma (FIPA) 2, 3.
• GNAS mutations have been associated with McCune-Albright syndrome, a disease that can cause endocrine hyperfunction and tumors in several organs, including the pituitary 3.

Other Factors

• Pituitary adenomas can also be caused by non-genetic factors, such as hormonal imbalances and environmental factors, although the exact mechanisms are not fully understood 5.
• The development of pituitary adenomas may be influenced by a combination of genetic and non-genetic factors, and further research is needed to understand the underlying causes 5, 2, 3, 4, 6.