Endocrine Abstracts

Introduction: The association between thyroid cancer and thyrotoxicosis is rare and, in particular, autonomous hyperfunctioning metastasis of differentiated thyroid cancer (TC) are seldom described, with a prevalence of 0.71%. Althought most hyperfunctioning metastasis are derived from follicular thyroid cancer (FTC), metastasis from papillary thyroid cancer (PTC) have been also reported. Bone metastasis account for the majority of cases. Hyperfunctioning TC metastasis have been rarely associated with anti-TSH receptor antibodies (TRAbs).

Clinical case: A 53-year-old male patient came to our attention in April 2018 for a non-toxic multinodular goiter. Because the dominant nodule (4 cm) was indeterminate at high risk (TIR3B according to the Italian classification of 2023), thyroidectomy was suggested but the patient refused it. Four years later, after the appearance of asthenia, palpitations, weight and hair loss, hyperthyroidism with positive TRAbs (19.2 UI/l, n.v. <1.5) was diagnosed, and anti-thyroid drug (methimazole) and beta blocker were started. CT scan confirmed the multinodular goiter and showed suspicious cervical lymphadenopathies and lung metastasis. In October 2022, the patient underwent total thyroidectomy and central and lateral cervical lymph-nodes dissection. Histology showed a poorly differentiated thyroid cancer associated with classical subtype multifocal papillary TC (positive for somatic mutation in NRAS gene and in TERT promoter), with multiple metastatic lymph-nodes [T3a(m)N1bM1]. Treatment with LT-4, suggested at discharge, was tapered down two months later, due to thyrotoxicosis. Still, thyrotoxicosis persisted, TRAbs were still positive (15 U/l), and methimazole was re-started and titrated up to 40 mg/day. In February 2023 the patient underwent 131-I treatment (81 mCi), after methimazole had been withdrawn for two days. Post-therapeutic SPECT-CT scan, performed ten days later, showed lymph-node and lung metastasis, which were avid of radioiodine. The patient was still hyperthyroid with positive TRAbs, at high title (19.60 UI/l). A month after 131-I treatment the levels of thyroid hormones started falling and methimazole was decreased to 15 mg/die.

Conclusions: We present the case of a patient with hyperfunctioning lung metastasis from thyroid cancer, with positive TRAbs. We hypothesize that TSH receptor expressed on the metastatic cells is activated by serum TRAbs, leading to the production of thyroid hormone and persistent hyperthyroidism.