SAT-409 - Metastatic Renal Cell Carcinoma to the Thyroid Presenting as Trab-Positive Subclinical Hyperthyroidism: A Metachronous Presentation 15 Years after Nephrectomy

Introduction:
Although thyroid metastasis from renal cell carcinoma (RCC) is rare despite the gland's vascularity, such metastasis may occur decades after nephrectomy. Sometimes, when suppressed TSH and positive TRAb suggest Graves disease, the possibility of coexistent metastatic disease may be overlooked. In this context, we present a case of solitary thyroid metastasis from RCC that was initially misdiagnosed as subclinical hyperthyroidism, emphasizing the significance of targeted immunohistochemistry (IHC) and surgical intervention.

Case Presentation:
A 66-year-old woman with a history of left nephrectomy for clear-cell RCC (2010), hysterectomy for uterine cancer, MGUS, and a strong family history (mother, father, sister with cancers) presented with persistent subclinical hyperthyroidism. Initially, biotin interference was suspected. However, thyroid function remained abnormal after discontinuation. Laboratory results included TSH 0.10 mIU/L (ref 0.35–4.94 mIU/L), free T4 1.19 ng/dL (ref 0.70–1.48 ng/dL), and positive TRAb 9.43 IU/L (ref 0–1.75 IU/L). Because TSH suppression with normal fT4 and TRAb positivity initially supported subclinical Graves disease, malignancy evaluation was deferred until neck ultrasound showed an enlarged, hypervascular thyroid with a large right-lobe nodule (4.9x2.4x3.5 cm). FNA yielded Bethesda III cytology.
At this point, a multidisciplinary review identified clear cell features, prompting consideration for metastatic RCC. Subsequently, PET-CT showed no extrathyroidal disease. Meanwhile, brain MRI revealed a left anterior parafalcine meningioma (8×14×10 mm). Based on these findings, total thyroidectomy was performed to establish a diagnosis, achieve regional control, and avoid chronic antithyroid therapy.
On pathology, the specimen revealed a 4.5 cm clear cell tumor with negative margins. IHC demonstrated PAX8, CD10, vimentin positivity with TTF-1, CK7, GATA3, chromogranin, and synaptophysin negativity, confirming metastatic RCC. Postoperatively, she achieved euthyroidism on levothyroxine and remains recurrence-free at 4 months on surveillance.

Conclusions:
1. Always consider thyroid metastasis from RCC in patients with a history of RCC, even decades after nephrectomy, particularly if atypical features accompany presumed Graves disease.
2. Concordance between Graves features and metastatic disease can mislead clinicians; indeterminate cytology requires renal IHC (PAX8/CD10/vimentin positive; TTF-1/CK7 negative).
3. Total thyroidectomy provides histological confirmation, local control, and avoids chronic antithyroid therapy in elderly patients.
4. In patients with strong family cancer histories, recommend genetic counseling and germline testing to guide further screening and care.
5. Biotin interference should be excluded when clinical and biochemical findings are discordant.

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