Credits

• Section Writer: Dr. Om J Lakhani
• Section Editor: Dr. Om J Lakhani

Q. What is the definition of Familial isolated pituitary adenoma (FIPA)?

• Stiles et al. define FIPA as "A term used to identify a genetic condition with pituitary tumors without other endocrine or other associated abnormalities." ^[1]

Q. Name the various germline mutation seen with Pituitary tumors?

• MEN – Menin (MEN1), CDKN1B (MEN4)
• FIPA  - AIP,  GPR101 (XLAG)
• SDH related pituitary adenoma- SDHA, B,  C, D
• Carney’s complex related- PRKAR1A
• Neurofibromatosis – NF1
• Pituitary blastoma- DICER1

Q. What are two broad categories of Familial isolated pituitary adenoma (FIPA)?

• FIPA with AIP mutation
• FIPA without AIP mutation

Q. What is fullform of AIP ?

• Aryl hydrocarbon interacting protein

Q. What was the basis of the origin of FIPA?

• In a search to identify tumors of the pituitary not having MEN1 or Carney’s complex lead to the discovery of FIPA

Q. What is homogenous FIPA, and what is heterogenous FIPA?

• Homogenous FIPA- same pituitary tumor syndrome amongst family members
• Heterogenous FIPA – different pituitary tumor syndromes

Q. Describe the frequency of various pituitary tumors in FIPA?

• Prolactinoma- 37%
• Somatotropinoma – 35%
• NFPA -14%
• Somatolactotropinoma – 6.4%
• Cushing’s disease 2.9%
• Less than 1-2% :
  • gonadotropinoma
  • Plurihormonal
  • thyrotropinoma

Pearl

• Prevalence of prolactinoma compared to the general population is slightly lower
• However, it is still the most common
• Somatoropinoma has a much higher prevalence compared to the normal population

Q. Loss of heterogenicity in which region has been associated with somatotropinoma in the general population?

• LOH in 11q13 is commonly associated with somatotropinoma

Q. What is the penetrance of AIP mutation?

• Variable penetrance – 20%

Q. Does pituitary adenoma with AIP mutation occur at a younger age?

• Yes

Q. Is gigantism more common with AIP mutation?

• Yes

Q. Is Non-functioning pituitary adenoma (NFPA) in FIPA more aggressive?

• Yes

Pearl

• Pituitary adenomas with FIPA are
• Occur at a younger age
• More aggressive
• Poor response to treatment
• Larger size
• Even within FIPA, those with positive AIP mutation have more significant of the above features compared to AIP negative ones

Q. Are AIP mutations germline or somatic?

• Germline only

Pearl

• FIPA – overall – prolactinoma most common
• FIPA with AIP mutation – Somatotropinoma is most common

Q. AIP mutation is more common in males or females?

• More in males

Q. Is pituitary apoplexy more common in AIP patients?

• Yes

Q. Are somatoropinomas with AIP mutation relatively resistant to treatment with Somatostatin analogs?

• Yes

Q. What is the mode of inheritance?

• It is autosomal dominant

Q. What % of pituitary adenoma are FIPA?

• 2-3%

Q. What is the role of the AIP gene?

• Exact role is not known
• But studies in mice have shown that AIP -/- tend to die in-utero because of defective cardiac development
• When Aip +/- develop a disease similar to humans – aggressive somatotropinoma

Q. How common is AIP mutation in FIPA patients?

• 25% of FIPA patients have AIP mutation

Q. What is the difference in patients of FIPA with AIP mutation and without?

Q. Give an outline for genetic testing in a patient with Pituitary adenoma?

• 

• *please read as XLAG instead of XLAq (Apologies for the typo)

Q.What are the tests done in patients screened to be AIP mutation-positive?

• Baseline
  • History, signs and symptoms, clinical examination
  • Baseline pituitary hormones
  • IGF1 and oGTT (for Growth hormone)
  • Baseline MRI