Endocrine Abstracts

Introduction: Multiple endocrine neoplasia–type 1 (MEN1) is an autosomal dominant cancer syndrome characterized by tumors in at least two of the following: parathyroid, endocrine pancreas, and anterior pituitary. MEN1 mutations may exhibit gonosomal mosaicism— a combination of somatic and germ-line tissue mosaicism. We present a family with gonosomal mosaicism in MEN1.

Case Presentation: A 43-year-old man presented with sudden neck enlargement, type 2 diabetes, hyperuricemia, and a family history of MEN1. His sister has a history of hyperprolactinemia, hypogonadal axis failure, hypothyroidism, and primary hyperparathyroidism, and she was diagnosed with a MEN1 mutation. The patient’s neck ultrasound revealed two focal lesions in the left supraclavicular fossa. Thin-needle biopsy showed monomorphic cells with a ‘salt and pepper’ chromatin pattern and pink cytoplasm. Differential diagnoses included neuroendocrine neoplasm (NEN) or medullary thyroid carcinoma (MTC). Tests indicated primary hyperparathyroidism with elevated IGF-1 and Chromogranin A. Radiological imaging revealed necrotic lymph nodes, chest masses, and pancreatic lesions. Surgical biopsy of a cervical lymph node detected atypical carcinoid (thymic NET G2). The patient received Octreotide, radiation therapy, and Everolimus. Genetic analysis identified a pathogenic MEN1 variant. Considering the MEN1 mutation in both siblings, first-degree relatives were examined. The mutation was absent in the parents’ blood despite the dominant inheritance pattern. Consanguinity was confirmed, suggesting parental genetic mosaicism. Analysing DNA from eyebrow hair follicles and cheek swabs (different germ-layer than blood) confirmed the father’s gonosomal mosaicism. The patient’s father shows no subjective symptoms.

Conclusions: The patient’s father should undergo periodic screening for MEN1 spectrum tumors. This case illustrates divergent MEN1 courses in siblings with the same mutation. Genetic testing should be extended to assess the potential spread of the mutation within other relatives. Only one case of gonosomal MEN1 mutation was described - it led to symptomatic disease there. No cases have reported asymptomatic gonosomal mosaicism.