ReviewFrontiers in endocrinology2026
Hyperfunctioning distant metastases in high-grade differentiated thyroid carcinoma arising from HRAS-mutated follicular thyroid carcinoma: a case report and literature review.
Review in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Hyperfunctioning distant metastases from differentiated thyroid carcinoma (DTC) are rare but increasingly reported. We report hormone-producing lung and bone metastases from an HRAS-mutated high-grade differentiated thyroid carcinoma (HGDTC) originating from follicular thyroid carcinoma (FTC), with a brief literature review. The metastases showed a marked response to radioactive iodine (RAI). Patient findings: A 68-year-old woman presented with an enlarging thyroid nodule and multiple pulmonary nodules after starting antithyroid therapy for Graves' disease. Histopathology confirmed HGDTC arising from FTC, and next-generation sequencing identified an HRAS Gln61Arg mutation. Thyrotoxicosis persisted after total thyroidectomy. A post-therapeutic whole-body radioiodine scan demonstrated iodine-avid pulmonary nodules and a left iliac bone lesion, consistent with hyperfunctioning distant metastases. Summary: After two RAI treatments, thyroid function shifted from hyperthyroidism to hypothyroidism, and follow-up chest computed tomography showed a significant reduction in pulmonary metastatic lesions. Conclusions: Hyperfunctioning distant metastases from DTC present diagnostic and therapeutic challenges. This case highlights the consideration of functioning metastases in persistent post-thyroidectomy thyrotoxicosis and demonstrates the potential effectiveness of RAI therapy when metastatic lesions retain iodine avidity. Oncogenic mutations such as HRAS may contribute to the pathophysiology of hormone-producing metastases and provide insights into tumor differentiation and therapeutic responsiveness.
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