Endocrine Abstracts

A 16-year-old female presented with secondary amenorrhoea. Menarche was age 14 years and periods were less frequent over the preceding 12 months. There was no galactorrhoea, headache or visual field disturbance and no known family history of pituitary disease, tall stature or infertility. There were no clinical signs of Cushing’s disease or acromegaly and visual fields were full to confrontation. Height was 160 cm. Investigations showed a prolactin of 2,452 mIU/l (RR 102-496). Insulin like growth factor-1 and random growth hormone were measured at 39.6 nmol/l (RR 16.8-70.9) and 0.5 ng/ml respectively. Magnetic resonance imaging of the pituitary demonstrated a 7.8 mm T2 hyperintense pituitary lesion located centrally within the gland which enhanced post gadolinium. A diagnosis of microprolactinoma was made and cabergoline was titrated to 750 micrograms once weekly with prolactin normalising at 3 months follow-up (358 mIU/l). Pituitary magnetic resonance imaging at 4 years follow-up showed the prolactinoma had decreased to 3.0 mm in diameter with less conspicuous contrast enhancement and T2 hyperintensity. Due to age of onset, germline testing was undertaken with the R217 panel including genes associated with pituitary tumours, which revealed a deletion c.442_444del (p.Leu148del) located in exon 3 of the aryl hydrocarbon receptor interacting protein gene (AIP). The amino acid change causes an in-frame deletion affecting a highly conserved residue likely disrupting the FKBP-like domain. Functional testing for this variant has been initiated. In silico protein modelling suggests this has a deleterious impact on protein folding and inter-strand bonding which will impair the AIP protein core. VarSome classifies this as variant of uncertain significance based on protein length changing (ACMG PM4) and it is not found within the gnomAD database (ACMG PM2). Genetic screening of family members is being pursued to determine if it is a de novo variant.