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Germline AIP mutations uncommon in patients with sporadic pituitary adenomas
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Aryl-hydrocarbon receptor interacting protein genetic testing should be limited to patients younger than age 40 years who are diagnosed with apparently sporadic large pituitary adenomas, according to study findings published in The Journal of Clinical Endocrinology & Metabolism.
Germline mutations of the aryl-hydrocarbon receptor interacting protein (AIP) gene are associated with a predisposition to pituitary adenomas, according to background information in the study. About half of patients with familial acromegaly demonstrate AIP mutations.
Researchers studied the prevalence of germline AIP mutations in 443 patients with pituitary adenomas of varying histotypes between June 2007 and September 2010 at Bicêtre Hospital in France. The patients had no family history of pituitary adenomas or multiple endocrine neoplasia.
The adenomas were divided into three categories — microadenomas (larger diameter <10 mm), macroadenomas (larger diameter between 10 mm and 29 mm) and giant adenomas (larger diameter = 30 mm).
Researchers screened the entire coding sequence of the AIP gene for germline mutations.
They detected AIP mutations in 16 (3.6%) of the 443 patients, including six of 148 patients (4.1%) with prolactinomas; six of 148 patients (4.1%) with acromegaly; three of 44 patients (6.8%) with corticotropic adenomas; and one of 113 patients (0.9%) with nonfunctioning adenomas. None of the six patients with thyrotropic adenomas expressed the mutation.
The patients with AIP mutation were younger at diagnosis than those without (23.6 years vs. 43.6 years, P<0.00001). Researchers detected the mutation in 7.2% (16 of 222) patients diagnosed at age younger than 40 years. They did not detect the mutation in any patients diagnosed after age 40 years.
Thirteen of the 16 patients (81.2%) found to have the mutation had either macroadenomas (n=11) or giant adenomas (n=2), and six of the 16 patients with the mutation (37.5%) had pure or mixed GH-secreting/prolactin-secreting (PRL) adenomas.
Researchers studied families of seven of the patients found to have the AIP mutation and, in each case, they discovered one asymptomatic parent carried the same mutation.
“This large prospective cohort study confirms the very low prevalence of germline AIP mutations in patients with apparently sporadic pituitary adenomas,” the researchers wrote. “We propose to limit AIP testing to patients diagnosed before age 40 with apparently sporadic large pituitary adenomas, especially GH- or PRL-secreting adenomas.”
The researchers also proposed AIP genetic testing for all children with pituitary adenomas because the mutations are found in up to one-quarter of pediatric cases.
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