Introduction: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are responsible for 1530% of familial isolated pituitary adenomas (FIPA). We report a 4-generation FIPA kindred with a heterozygous AIP gene deletion in exon 2, highlighting the benefits of genetic screening and management challenges in affected subjects and asymptomatic carriers.
Patients: A 45y woman died of a spinal ependymoma (obligate carrier). Her 18y son showed lethargy over the following months attributed to grief. However, investigations due to headache revealed hypopituitarism and a clinically non-functioning PA was diagnosed. Two years later, his 185 cm 18y-brother was diagnosed with a sparsely-granulated PA co-expressing PRL&GH. Fourteen-years after operation his IGF-1 was repeatedly raised with small increase in his tumour remnant. Lanreotide treatment was started and surgery is planned. A Rathkes cyst was detected in a bulky gland in their eupituitary 17y mutation carrier sister when she was first screened, which is now regressed. However, after 8y follow-up a 4 mm-microadenoma became visible, with normal PRL, IGF-1 and OGTT-GH nadir 0.38 μg/l. Their 27y second-cousin presented amenorrhoea after cessation of oral contraceptive, hyperprolactinaemia and 2xULN IGF-1. Her MRI showed 2 pituitary microadenomas, corresponding to a 6 mm-somatotropinoma on the right and a 4 mm-prolactinoma on the left, confirmed histologically.
Discussion: Of 14 subjects with AIP mutations, 4 have PA, 1 ependymoma and 7 are asymptomatic (penetrance 29%). Ependymomas were described with loss of genetic material at 11q13-locus, but has not been described in patients with AIP mutations. The slow regrowth of the tumor in the brother suggests that long-term follow-up is needed. Bulky pituitary and not fully suppressed GH on OGTT can represent challenges in AIP mutation carrier teenager females. Multiple PAs with different secretory profiles may arise in the pituitary of these patients. Genetic screening and baseline review with follow-up of younger subjects is recommended in AIP mutation-positive families.
20 May 2017 - 23 May 2017