SUN-419 - Parathyroid Lesions Masquerading as Intrathyroidal Nodules with Incidental MEN1 Mutation on Molecular Testing: A Case Series

Intrathyroidal parathyroid lesions are rare, reported in approximately 1 to 6% of parathyroid adenomas, and may present as thyroid nodules with suspicious sonographic features, prompting fine-needle aspiration. Cytological differentiation from thyroid lesions is often challenging and may result in indeterminate diagnoses.
We present two women in their 70s with a history of primary hyperparathyroidism diagnosed on routine blood work, and no known family history of Multiple Endocrine Neoplasia Type 1 or endocrine tumors, who underwent evaluation for hypoechoic thyroid nodules. Fine-needle aspiration demonstrated indeterminate cytology, consistent with atypia of indeterminate significance (Bethesda III). Molecular analysis using ThyroSeq V3 GC revealed strong expression of the Parathyroid Hormone and Chromogranin A (CHGA) genes with low expression of thyroid cell-related genes. A MEN1 mutation was also identified in the sample. Both patients underwent parathyroidectomy, with surgical pathology confirming hypercellular parathyroid tissue. They are undergoing targeted biochemical and imaging evaluation for MEN1-associated tumors; a pancreatic cyst was identified in one patient.
Somatic MEN1 mutations have been reported in approximately 12-35% of sporadic parathyroid adenomas, and represent a key mechanism of tumorigenesis. With increasing use of molecular testing platforms such as ThyroSeq in thyroid nodule evaluation, incidental detection of parathyroid tissue and MEN1 mutations is likely to become more common in clinical practice. However, molecular assays do not distinguish somatic from germline alterations. Detection of a MEN1 mutation in this setting is not diagnostic of Multiple Endocrine Neoplasia 1. This creates uncertainty in interpretation and management, and the optimal approach to these findings remains unclear. In the presence of additional findings, such as pancreatic lesions, the distinction between somatic and germline alterations becomes more clinically relevant. A risk-based strategy incorporating selective germline testing and targeted evaluation for MEN1-associated tumors may be considered in selected cases.

These cases highlight the diagnostic overlap between thyroid and parathyroid lesions and emphasize the importance of clinical correlation in interpreting incidental molecular findings to avoid unnecessary syndromic workup.

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