SUN-360 - Early Radioactive Iodine Non-Avidity in BRAF-Positive Papillary Thyroid Microcarcinoma with Autoimmune Thyroiditis and Familial RAI Resistance

Papillary thyroid carcinoma (PTC) usually responds to radioactive iodine (RAI), yet a subset, including early-stage microcarcinoma, exhibits intrinsic RAI resistance. BRAF p.V600E mutations and autoimmune thyroiditis influence tumor behavior, but their combined effect on RAI avidity remains unclear.

A 60-year-old asymptomatic woman with a daughter treated for RAI-refractory PTC underwent screening. Thyroid function was normal, and ultrasound showed multiple subcentimeter nodules (largest 8 mm) initially classified as TI-RADS 3–4. Serial imaging demonstrated interval growth, progression to TI-RADS 4–5, and features suggestive of thyroiditis. Two consecutive fine-needle aspiration biopsies showed atypia of undetermined significance (AUS). Molecular testing from aspirates identified a BRAF p.V600E mutation. Additional testing showed subclinical hypothyroidism with positive anti–thyroid peroxidase antibodies. Given repeated indeterminate cytology, oncogenic mutation, and a first-degree relative with RAI-refractory PTC, total thyroidectomy was pursued. Histopathology confirmed multifocal papillary thyroid microcarcinoma (largest 8 mm) without extrathyroidal or nodal involvement, coexistent with chronic lymphocytic thyroiditis.

Postoperative serum thyroglobulin was low; however, anti-thyroglobulin antibodies were elevated, consistent with Hashimoto’s thyroiditis and limiting the reliability of thyroglobulin as a tumor marker. RAI therapy (50 mCi) was administered after adequate TSH stimulation, and post-therapy whole-body scan showed no cervical or distant iodine uptake, indicating intrinsic RAI non-avidity.

BRAF p.V600E is associated with adverse outcomes in PTC, yet its prognostic value varies across populations. In this case, BRAF positivity occurred in multifocal microcarcinoma lacking classic aggressive histologic features, illustrating discordance between molecular and morphologic risk. Detection of BRAF mutation in repeatedly indeterminate cytology provided supportive molecular evidence for definitive surgery. Coexistent chronic lymphocytic thyroiditis has been linked with less aggressive tumor behavior and may explain the indolent histology despite oncogenic mutation. Conversely, the family history of RAI-refractory disease and the patient’s early lack of iodine avidity raise the possibility of shared biological factors contributing to intrinsic RAI resistance.

This case illustrates a rare convergence of BRAF-positive papillary microcarcinoma, autoimmune thyroiditis, and early RAI non-avidity, underscoring the value of molecular testing in indeterminate nodules and individualized risk assessment. While ATA-guided care favors conservative management for low-risk microcarcinoma, additional molecular and familial risk factors in this patient influenced decision-making within a risk-adapted approach.

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