Thyroglobulin Tsunami: Awash in a Sea of T3 Thyrotoxicosis

Introduction : Thyroid malignancy rarely presents as a massive hypermetabolic metastatic process, let alone as "T3 thyrotoxicosis" with an extraordinary thyroglobulin level.

Case Description : A 55 year-old female came to our ER with elbow pain, diagnosed as a distal humeral fracture.

One year prior, she went to another hospital for right shoulder and back pain. A large multinodular goiter was noted. CT revealed a large thyroid mass invading the superior mediastinum and anterior chest wall including the sternum. Apparent liver and pulmonary metastasis were reported. She underwent FNAB of an enlarging neck mass with finding of "atypical cells of unknown significance" TSH at time was was < 0.01 uIU/mL (0.36-3.74uIU/mL), Free T4 0.44 ng/dL (0.76-1.46ng/dL), Free T3 4.16 pg/mL (2.18-3.98pg/mL). Thyroglobulin 17,875.4ng/mL (1.5-38.5ng/mL) with negative thyroglobulin antibodies, alkaline phosphatase 68 U/L(45 - 117 U/L). Patient received metoprolol for sinus tachycardia but no anti-thyroid medications. Patient was then discharged but lost to follow-up. 

In our ER, besides the bone pain, she complained of increasing severe palpitation and weight loss. She appeared very cachectic, moribund and hypermetabolic with Burch-Wartofsky score >45. A massive multinodular goiter greater than 10 cm by 10 cm attached to the sternum, fixed and warm was felt on palpation. CT revealed multiple expansile osteolytic masses involving most of sternum, clavicles, right first rib, multiple thoracic verterbrae, innumerable hematogenous pulmonary mets, hepatic mets, and pelvic lesions. Initial TSH < 0.05 uIU/mL(0.47-4.7 uIU/mL), Free T4 0.81 ng/dL (0.8-2.2 ng/dL), Free T3 10.3 pg/mL (2.77-5.27 pg/mL), Thyroglobulin 89,970.0 ng/mL (2.8-40.9 ng/mL) with negative thyroglobulin antibodies, alkaline phosphatase 293 U/L (37-126 U/L). She was treated with propranolol, methimazole, steroids, SSKI and phenobarbital. Working diagnosis was suspected widely metastatic functional thyroid cancer resulting in thyroid storm. Patient declined a tissue biopsy, opted for comfort care only, and expired within 4 days.

Discussion : Though this is rare, some patients with functional widely metastatic thyroid cancer have high serum triiodothyronine (T3) and normal thyroxine (T4) levels, resulting in a "T3 thyrotoxicosis". Usually, cases are follicular thyroid cancer. Mechanism can be explained by elevated activity of Type 1 and Type 2 iodothyronine deiodinases in the tumor tissue. Bone (usually osteolytic lesions) and other organ involvement often occur. Unfortunately, we were unable to obtain a tissue diagnosis. In retrospect, propylthiouracil might have been better choice for blocking T4 to T3 conversion. The extraordinary thyroglobulin level reflects the massive tumor burden in this case.