ESPE Abstracts

Aim: We describe the natural history, treatment, and clinical outcomes of Multiple Endocrine Neoplasia type 2B (MEN2B) caused by the M918T RET pathogenic variant.

Methods: Retrospective case notes review of all young people <18 years presenting to a quaternary paediatric endocrinology referral centre in the UK between 2005-2023 who have MEN2B caused by the M918T pathogenic variant in the RET proto-oncogene.

Results: Twelve children (7F, 58.3%, median age at genetic diagnosis 3.5yrs, range 0.1-16) with a confirmed heterozygous c.2753T>C M918T RET pathogenic variant (de novo in 66.7% (n = 8), maternally inherited in 25% (n = 3), and of unknown inheritance in 8.3% (n = 1)) were included. Eleven (91.7%) had gastrointestinal manifestations: constipation (83.3%, n = 10), intestinal ganglioneuromatosis (50%, n = 6), and gallstones (25%, n = 3). Mucosal neuromas were found in 58.3% (n = 7) and alacrima in 25% (n = 3). Three children (25%) had clinically palpable disease. All had thyroidectomy with central lymphadenectomy (median age 4.5yrs, range 0.3-16); two had lateral neck dissections. Preoperative calcitonin was 85ng/L (range 23-7120) with an undetectable calcitonin achieved postoperatively in 33.3% (n = 4). Medullary thyroid cancer was confirmed on histopathology in 91.7% (n = 11); one child had c-cell hyperplasia. Four children (33.3%) had nodal involvement. One child had metastasis to surrounding mediastinal structures and received adjuvant EBRT. Three children had later biochemical and/or clinical recurrence requiring reoperation (n = 1) and/or selpercatinib or vandetinib treatment (n = 3, treated for a range of 1-3 years). No child developed a phaeochromocytoma during the study surveillance period. One child died of a respiratory arrest unrelated to thyroid pathology.

Conclusions: Early diagnosis and thyroidectomy are essential for children with M918T-associated MEN2B. Gastrointestinal manifestations are characteristic and should raise diagnostic suspicion of this rare disease. Selective RET tyrosine kinase inhibitors show therapeutic efficacy in progressive disease.