P. Romanet*a (Dr), A. Boukerrounia (Dr), T. Cunya (Dr), G. Mougela (Dr), T. Anjoua (Dr), M. Pertuita (Dr), A. Lagardea (Dr), M. Viergea (Dr), E. Sonnetb (Dr), I. Raingeardc (Dr), H. Dufoura (Prof), P. Niccolid (Prof), D. Gaillarde (Prof), V. Kerlanb (Prof), A. Barliera (Prof)

a APHM - Aix Marseille Univ, Marseille, FRANCE ; b CHU de Brest, Brest, FRANCE ; c CHU de Montpellier, Montpellier, FRANCE ; d IPC, Marseille, FRANCE ; e CHU de Reims, Reims, FRANCE

* pauline.romanet@ap-hm.fr

Background: Approximatively 5 to 7% of pituitary neuroendocine tumors are inherited1. Prolactinomas represent 46 to 66% of pituitary adenomas1,2, but the prevalence of germline mutations is poorly known.

We presented here the first study, to our knowledge, focusing on hereditary predisposition to prolactinomas.

Objective: We studied the prevalence of germline mutations in a large cohort of patients with isolated prolactinoma.

Material and methods: We retrospectively analyzed the genetic data of patients addressed for genetic testing of MEN1, AIP, and CDKN1B between 2003 and 2020. In genetically negative patients with macroprolactinoma, we sequenced by Sanger SF3B1, a gene recently identified as driver in prolactinomas at the somatic level3.

Results: We included 507 patients: 81 with microprolactinoma (16%), 379 with macroprolactinoma (75%), 47 unknowns, 49/507 in a family context (10%). Among them 14 had a (likely) pathogenic variant in MEN1 or AIP, none in CDKN1B; none was over 30 years old at the prolactinoma diagnosis, all developed macroprolactinomas except one Comorian teenager who carried an AIP mutation with a founder effect in this population4. The prevalence of germline mutations in patients with isolated macroprolactinoma before 30 years was 4% (10/258) in a sporadic context, and 15% (3/20) in a family context. The prevalence in sporadic case before 18 years was 12% in men (4/33) and 7% in women (4/57). No R625H SF3B1 germline mutation was identified in 265 patients with macroprolactinomas

Conclusion: This data confirms that 30 years seems to be a good cut-off age for genetic testing in macroprolactinoma. Particular attention should be paid to young patients and patients in a family context. There is no evidence to recommend genetic testing in patients with microprolactinoma.

1 Review in Aflorei & Korbonits, J Neurooncol 2014

2 Review in Daly, Tichomirowa & Beckers Best Pract Res Clin Endocrinol Metab 2009

3 Li et al, Nat Commun 2020

4 Cuny et al, Eur J Endocrinol 2013

The author has declared no conflict of interest.