Endocrine Abstracts

Introduction: Introduced by Beckers in 1999, familial isolated pituitary adenoma (FIPA) describes families with pituitary adenomas. FIPA are larger, more aggressive tumours, with earlier age of onset compared to sporadic pituitary adenomas. They are non-syndromic (e.g., not part of MEN1, MEN4, Carney complex, McCune-Albright, etc). Pathogenic variants within the aryl hydrocarbon receptor interacting protein (AIP) gene have been identified in 10-20% of FIPA families and 50% of growth hormone (GH) producing tumour families. Rarely, duplication of the orphan G protein-coupled receptor (GPR101) causes X-linked acrogigantism (GH- and prolactin-producing tumours). The genetic cause for the majority of FIPA families remains unknown. We present two brothers with non-functioning pituitary tumours.

Case: Case-1: A 54-year-old male from a non-consanguineous family presented with reduced libido and erectile dysfunction. Medical history included type 2 diabetes and primary hypothyroidism. Investigations demonstrated mild hyperprolactinaemia and hypogonadotropic hypogonadism. Brain imaging confirmed a 10x9x9mm non-functioning pituitary adenoma, which was managed conservatively. Case-2: A 58-year-old male (brother of case-1) had an incidental 16x20x13mm pituitary macroadenoma discovered during investigation for a stroke. Medical history included primary hypothyroidism. Investigations demonstrated mild hyperprolactinaemia. A non-functioning pituitary adenoma was resected. Subsequent sequencing and dosage analysis of the endocrine neoplasia gene panel (MEN1, CDC73, AIP, CDKN1B, RET) revealed no pathogenic variants. The negative AIP gene analysis in one brother plus the absence of other tumours or syndromic features in both brothers, confirmed FIPA.

Conclusion: This report emphasises the high frequency of variant-negative FIPA. The genetics of familial and apparently sporadic pituitary tumours is ongoing and new candidate genes have been identified, however, causative evidence is required. Offsprings of affected individuals have a 50% chance of inheriting unknown autosomal dominant variants with reduced penetrance. Detailed family history is important in prompting genetic and clinical screening to achieve early diagnosis and treatment of FIPA.