Endocrine Abstracts

The coexistence of Graves disease (GD) and thyroid carcinoma used to be considered uncommon, but association between the two is being progressively acknowledged.

Case report: We present the case of a 69-year-old woman with a 10 year history of GD who was referred to our clinic for fatigue, sweating, palpable cervical mass and weight loss. She was treated only in the previous 5 months with block and replace therapy. Laboratory workup at admission showed suppressed TSH (0.0003 µUI/ml), high levels of FT4 (31.08 pmol/l) and T3 (>600 ng/dl), positive TRAb (30.85 UI/l). Thyroid ultrasound revealed a multinodular goiter with two hypoechoic macronodules in the right lobe and isthmus classified as TIRADS 4. Technetium-99m scintigraphy showed multinodular goiter with a cold nodule over the right lobe and fine-needle aspiration citology smears of the isthmic nodule were suggestive of follicular carcinoma oncocytic type. High doses of methimazole (40 mg/day) were required to lower thyroid hormone levels preop, but TSH remained suppressed. Total thyroidectomy along with lateral neck lymph node dissection were performed. Pathology yielded a diagnosis of background of GD with invasive PTC in the isthmic nodule with poorly differentiated areas and metastasis in a right lateral lymph node - pT4bpN1bST4G2R1LV1. Postoperative follow-up revealed high titers of thyroglobulin (>500 ng/ml) and antithyroglobulin antibodies (461.3 UI/ml) with a suppressed TSH off levothyroxine; cervical ultrasound demonstrated a small paratracheal remnant of thyroid tissue and nonspecific lymph nodes laterocervical bilateral. Whole body radioiodine scan after Thyrogen showed significant iodine uptake in the thyroid bed and retrosternally and additional ¹³¹I accumulation for both lungs. Patient received 100 mCi ¹³¹ with a drop in thyroglobulin level. Genetic profiling is pending.

Discussion: Genomic profiling allows personalisation of thyroid cancer therapy based on molecular information. A multi-step model of progression from well to poorly differentiated carcinoma has been proposed which includes 2 types of molecular events comprising ‘early’ events such as RAS and BRAF mutations and late ‘events’ as TERT and TP53 mutations. In this case we expect to find ‘early’ driver events like RAS/BRAF mutations which are the most prevalent in poorly differentiated cancer.

Conclusion: This case outlines the importance of further assessment for underlying malignancy when a nodular thyroid is present on the background of GD and genetic profiling of such malignant nodules to guide second stage therapy in the event of progressive disease after standard therapies.