Familial isolated pituitary adenoma (ORPHA:314777)
A rare, hereditary endocrine tumor characterized by a benign pituitary adenoma that is either secreting (e.g. prolactin, growth hormone, thyroid stimulating hormone) or non-secreting. Symptoms may occur due to either the hormonal hypersecretion and/or the mass effect of the lesion on local structures in the brain.
Epidemiology
Familial isolated pituitary adenoma (FIPA) prevalence is unknown. However, FIPA represents around 2-5% of pituitary adenoma cases. A female predominance is reported.
Clinical description
In FIPA, pituitary adenomas can be of any secretory type (e.g. prolactinoma, acromegaly, Cushing's disease, TSH-secreting) or can be non-secreting. FIPA kindreds usually have 2-4 members affected with pituitary adenomas, while larger numbers of affected patients per family can occur infrequently. In FIPA, pituitary adenomas generally begin at a younger age and are larger than corresponding sporadic non-FIPA cases. Pituitary adenomas in FIPA can cause symptoms due to hormonal hypersecretion and/or due to the mass effect of the pituitary adenoma on local structures in the brain (e.g. visual disturbance). In FIPA families with AIP mutations pituitary adenoma growth characteristics are often aggressive and hormonal hypersecretion may be marked.
Etiology
In up to 80% of FIPA families, the etiology of pituitary adenomas is unknown. However, mutations in the gene AIP (11q13.2 ) account for about 20% of FIPA kindreds. AIP is thought to act as a tumor suppressor gene. Pituitary adenomas due to germline AIP mutations are accompanied by a second hit of the other allele (e.g. deletion or mutation) and this is thought to favor or stimulate tumorigenesis.
Diagnostic methods
FIPA kindreds usually have 2-4 members affected with pituitary adenomas. Hormonal testing is used to identify abnormal hormonal secretion in FIPA. Magnetic resonance imaging (MRI) is used to confirm the presence and dimensions of a pituitary adenoma. AIP mutations can lead to pituitary apoplexy in FIPA kindreds, so MRI and hormonal signs of apoplexy may be present in affected family members.
Differential diagnosis
Differential diagnosis include multiple endocrine neoplasia type 1 and familial infantile gigantism, which may present as FIPA.
Genetic counseling
In children of FIPA cases with AIP mutations, the pattern of inheritance is autosomal dominant and, thus, there is a 50% risk of inheriting the mutation from an affected parent. For families with unidentified gene, an autosomal dominant inheritance pattern has been suggested. Large international studies have shown that only about 20% of AIP mutation carriers eventually develop a pituitary adenoma.
Management and treatment
Pituitary adenomas in the setting of FIPA are generally managed according to guideline recommendations for non-FIPA pituitary adenomas. However, in FIPA families with AIP mutations, pituitary adenomas (often growth hormone secreting) can be large and poorly responsive to treatment with surgery and medical therapy.
Prognosis
Formal outcome studies for patients with FIPA as compared with sporadic pituitary adenoma patients have not been performed. However, due to larger tumor size, younger age at onset and lower responses to medical therapies (particularly in FIPA families with AIP mutations), hormonal and tumoral effects may be more difficult to control and may require a larger burden of treatment.

                            Last update: 
                            September 2019


                            - Expert reviewer(s): 
                            Pr Albert BECKERS  - Dr Adrian DALY