AIP variant causing familial prolactinoma
- PDF / 689,108 Bytes
- 5 Pages / 595.276 x 790.866 pts Page_size
- 111 Downloads / 181 Views
AIP variant causing familial prolactinoma David M. Carty1 · Rachael Harte1 · Russell S. Drummond1 · Rebecca Ward2 · Kesson Magid3 · David Collier3 · Martina Owens4 · Márta Korbonits3 Accepted: 18 September 2020 © The Author(s) 2020
Abstract Pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene are increasingly recognised as a cause of familial isolated pituitary adenoma. AIP-associated tumours are most commonly growth hormone (GH) producing. In our cohort of 175 AIP mutation positive patients representing 93 kindreds, 139 (79%) have GH excess, 19 have prolactinoma (17 familial and 2 sporadic cases) and out of the 17 clinically non-functioning tumours 4 were subsequently operated and found to be GH or GH & prolactin immunopositive adenoma. Here we report a family with an AIP variant, in which multiple family members are affected by prolactinoma, but none with GH excess. To our knowledge this is the first reported family with an AIP pathogenic variant to be affected solely by prolactinoma. These data suggest that prolactinoma families represent a small subset of AIP mutation positive kindreds, and similar to young-onset sporadic prolactinomas, AIP screening would be indicated. Keywords Prolactinoma · AIP mutation · Familial · Pituitary
Introduction Although most pituitary tumours arise sporadically, in around 5% of cases there is a familial presentation. Familial isolated pituitary adenoma (FIPA) is defined as pituitary tumours occurring in two or more family members, in the absence of other recognised genetic syndromes [1]. Pathogenic variants in the aryl hydrocarbon-interacting protein gene (AIP) have been increasingly recognised since their initial description in 2006, and are reported in up to 15% of FIPA families [2]. Pituitary tumours affect 17–23% of individuals with a pathogenic AIP variant [3, 4]. AIP associated tumours are most commonly growth hormone (GH) * David M. Carty [email protected] 1
Department of Diabetes, Endocrinology & Clinical Pharmacology, Glasgow Royal Infirmary, Glasgow, UK
2
University of Exeter Medical School, Exeter, UK
3
Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
4
Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
producing; presenting at a younger age with large tumours that are relatively resistant to conventional medical therapy, with more male patients recognised [2]. Around 10% of AIPrelated pituitary tumours are solely prolactin producing [5, 6]; all reported prolactinoma cases have either had family members with GH excess or were simplex cases of AIP mutation positive sporadic prolactinomas. Here we report a family with homogenous familial prolactinoma segregating a pathogenic AIP nonsense variant.
Case 1 A 46-year-old man presented in 2012, having been referred from ophthalmology with a 6-month history of visual blurring; Goldmann perimetry demonstrated bitemporal hem
Data Loading...
