Pathogenesis of familial acromegaly

Abstract

Familial acromegaly may occur as a component of syndromes of multiple endocrine neoplasia or as isolated familial somatotropinoma (IFS), which is included in the spectrum of familial isolated pituitary adenoma (FIPA). We review the pathogenesis of IFS, from the detection of loss of heterozygosity at chromosome 11q13 and establishment of linkage to this chromosome region to the description of germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Approximately 40% of IFS families harbor an AIP mutation. In addition, we summarize the clinical features of IFS families with AIP mutations: The adenomas are diagnosed at a young age and are larger than in IFS patients without AIP mutations or in sporadic somatotropinomas, indicating more aggressive disease.