Endocrine Abstracts

Introduction: It has been estimated that 15–20% of FIPA families harbor an AIP gene mutation (AIPmut). To our knowledge ~50 sequence variants -pathological and otherwise- have been described to date. We report a new FIPA family with an extensive genealogy, in which 4 members have pituitary adenomas in the setting of a novel AIPmut.

Patients and methods: The index patient is a 37-year-old man, who presented with childhood onset of somatotropinoma and underwent surgery and radiotherapy at the age of 17. His uncle (now aged 70 years), was diagnosed with a somatotropinoma at the age of 16, and also treated with surgery and radiotherapy. The sister of this latter man (the 72-year-old aunt of the index case) presented with secondary amenorrea at age 18, and was later diagnosed with a macroadenoma at the age of 48 after she complained of visual disturbances. She also underwent surgery and radiotherapy. The fourth affected member is the 65-year-old cousin of the latter two patients. He is 1.97 cm tall, with a long standing hypogonadal phenotype; he had hypopituitarism affecting the gonadal, thyroid and somatotrope axes. His MRI shows a wide sella with an eroded floor, and there is a clinical suggestion of potential apoplexy in the past. A genealogic tree was drawn and due to the FIPA presentation, germline AIP sequencing was performed and showed all four affected subjects to have a novel c.543delT AIPmut, which would predict a truncated AIP protein.

Conclusions: This 4-member AIPmut positive FIPA family with a presentation that typifies the range of clinical scenarios encountered in AIPmut carriers with pituitary adenomas. As the disease presentation was quite aggressive in these cases and as early intervention has appeared to control disease in some of the individuals, we are currently screening for AIPmut carriers among the family.