Sporadic pituitary adenomas: the role of germline mutations and recommendations for genetic screening

Although most pituitary adenomas occur sporadically, these common tumors can present in a familial setting in approximately 5% of cases. Germline mutations in several genes with autosomal dominant (AIP, MEN1, CDKN1B, PRKAR1A, SDHx) or X-linked dominant (GPR101) inheritance are causative of familial pituitary adenomas. Due to variable disease penetrance and occurrence of de novo mutations, some patients harboring germline mutations have no family history of pituitary adenomas (simplex cases). Areas covered: We summarize the recent findings on the role of germline mutations associated with familial pituitary adenomas in patients with sporadic clinical presentation. Expert commentary: Up to 12% of patients with young onset pituitary adenomas (age at diagnosis/onset ≤30 years) and up to 25% of simplex patients with gigantism carry mutations in the AIP gene, while most cases of X-linked acrogigantism (XLAG) due to GPR101 duplication are simplex female patients with very early disease onset (<5 years). With regard to the syndromes of multiple endocrine neoplasia (MEN), MEN1 mutations can be identified in a significant proportion of patients with childhood onset prolactinomas. Somatotroph and lactotroph adenomas are the most common pituitary adenomas associated with germline predisposing mutations. Genetic screening should be considered in patients with young onset pituitary adenomas.