Characteristics of Familial Isolated Pituitary Adenomas

AIP = Aryl hydrocarbon receptor interacting protein gene; FIPA = Familial isolated pituitary adenomas; GH = Growth hormone.

The predicted effect on amino acid sequence and clinical details are outlined briefly.
AIP = Aryl hydrocarbon receptor interacting protein; GH = Growth hormone; PRL = Prolactin.

Authors and Disclosures

Adrian F Daly,¹ Jean-François Vanbellinghen,² Albert Beckers <sup>3

1</sup>University of Liège, Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium
²University of Liège, Department of Molecular Genetics, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium
³Department of Endocrinology, CHU de Liège, University of Liege, Domaine Universitaire du Sart Tilman, Liège, Belgium

Disclosure: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.

Sidebar: Key Issues

• Approximately 5% of pituitary adenomas occur in a familial setting.
  
  

• Familial isolated pituitary adenomas (FIPA) is a new clinical condition characterized by the occurrence of pituitary adenomas of any tumor type among related family members in the absence of multiple endocrine neoplasia type 1 or Carney complex.
  
  

• In FIPA, families may either be homogeneous (same pituitary tumor type in all affected members) or heterogeneous (various pituitary tumor types in the same family). Over 90 FIPA families involving two to four affected members have been described.
  
  

• In the setting of FIPA, patients have more aggressive tumors and present at a younger age than patients with sporadic pituitary tumors. In multigenerational FIPA families, children/grandchildren present with pituitary tumors earlier than their parents/grandparents.
  
  

• Together, prolactinomas and somatotropinomas comprise 75% of the tumors seen in FIPA and virtually all families have at least one member with a prolactinoma or somatotropinoma.
  
  

• Mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) are seen in a minority (15%) of FIPA families and half of homogeneous acromegaly families have AIP mutations.
  
  

• Most AIP mutations that occur in the setting of FIPA would predict truncation of the AIP protein at or before key structural components near the carboxy terminal.
  
  

• In FIPA families with AIP mutations, patients within the same family may have different hormonal or anatomopathological pituitary tumor features. Unrelated FIPA families with the same AIP mutation can have different pituitary tumor characteristics among affected members.
  
  

• The penetrance of pituitary disease in FIPA families with AIP mutations is often over 50%, suggesting an autosomal dominant disease with incomplete penetrance.