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.