Most pituitary adenomas are sporadic, but several familial syndromes are associated with pituitary tumors. In each, the pituitary tumor is one of several tumors that appear across the body or across a family, and each is tied to a particular gene.
MEN
MEN (multiple endocrine neoplasia) is an autosomal dominant syndrome, inherited when one copy of the altered gene is enough, that predisposes the person to parathyroid, pancreatic islet, and pituitary adenomas. It is caused by mutations in the MEN1 (menin-1) gene, and a related MEN-like 1 phenotype is caused by mutations in the CDKN1B gene. About half of the patients with MEN develop prolactinoma, while Cushing’s disease and acromegaly are rare.
Carney complex
Carney complex is characterized by spotty skin pigmentation and endocrine tumors such as testicular, adrenal, and pituitary adenomas (20% of patients manifest Cushing’s disease). In a subset of patients it is associated with a mutation in the PRKAR1A gene, which encodes the R1α regulatory subunit of protein kinase A.
McCune-Albright syndrome
McCune-Albright syndrome is caused by a post-zygotic mosaic mutation, one arising after fertilisation and present in only some of the body’s cells, in the GNAS gene, which encodes the Gs protein; the mutation decreases the GTPase activity of the G protein and therefore causes constitutive production of cAMP. It is manifested by polyostotic fibrous dysplasia, by skin pigmentation, and by multiple endocrine tumors such as acromegaly, adrenal adenoma, and autonomous ovarian function.
Familial acromegaly
Familial acromegaly is a rare disorder in which family members have either acromegaly or gigantism. A subset of families with familial acromegaly harbor mutations of AIP that predispose them to acromegaly (see Molecular pathogenesis of pituitary adenomas).
The pituitary tumors named in these syndromes are hormone-secreting. Adenomas that produce no clinically active hormone come to attention differently, through the compression they cause.