ESA-SRB-AOTA 2019

Hyperthyroidism due to metastatic T3-secreting follicular thyroid carcinoma: A case report and literature review (#779)

Annabelle M Warren 1 , Mark Pace 1 , Suzanne Silberberg 2 , Leon Bach 1 , Duncan Topliss 1
  1. The Alfred Hospital, Melbourne, VIC, Australia
  2. Unaffiliated, Melbourne, VIC, Australia

Background: The identification of hyperthyroidism during work up of a thyroid nodule is generally regarded as reassuring for the presence of thyroid cancer.

 Case: A 66-year-old woman with a longstanding multinodular goitre developed mild T3-toxicosis with TSH <0.01 mU/L (0.5-5.5mU/L), free T4 21.5 pmol/L (11.0-22.0 pmol/L) and free T3 7.3pmol/L (3.1-6.4pmol/L). Her goitre had enlarged and she had lost weight but she had no other symptoms or signs of hyperthyroidism.

Thyroid ultrasound revealed three 50-60 mm thyroid nodules, solid, isoechoic, smooth margins, wider-than-tall, with macrocalcification (TIRADS 4). A thyroid 99mTc radionuclide scan unexpectedly showed absent uptake.

She underwent total thyroidectomy. Histopathology revealed a 65 mm widely invasive follicular thyroid carcinoma with extensive capsular and vascular invasion. Repeat thyroid function 6 weeks post-operatively demonstrated worsening T3-toxicosis with TSH <0.01mU/L (0.5-5.5 mU/L), free T4 21.5 pmol/L (11.0-22.0 pmol/L) and free T3 12.8pmol/L (3.1-6.4 pmol/L). The patient developed anxiety and tachycardia. Levothyroxine therapy was ceased. Unstimulated serum thyroglobulin level was 23,902ug/L. Positron emission tomography and radioactive iodine (RAI) whole body scans demonstrated extensive iodine-avid and non-avid nodal, lung, and skeletal metastatic disease. Following administration of RAI, T3 levels declined and levothyroxine was recommenced.

Discussion: Thyrotoxicosis caused by thyroid hormone-producing functional metastatic thyroid cancer is rare, with 54 cases reported from 1946-2019 (1-4). Functional status is associated with widely metastatic disease, follicular thyroid carcinoma, prior structural thyroid abnormalities (e.g. multinodular goitre), higher serum thyroglobulin levels, and bony metastases more commonly than lung metastases (1, 5). By their nature, functioning metastases are sensitive to radioiodine. Several pathophysiological mechanisms of thyrotoxicosis caused by functional thyroid cancer are described (2, 6, 7).  

Conclusion: Hyperthyroidism due to thyroid cancer is rare, but the presence of clinical or biochemical hyperthyroidism should not exclude the diagnostic possibility of thyroid cancer.

  1. Tardy M, Tavernier E, Sautot G, Nove-Josserand R, Bournaud C, Houzard C, et al. [A case of hyperthyroidism due to functioning metastasis of differentiated thyroid carcinoma. Discussion and literature review]. Ann Endocrinol (Paris). 2007;68(1):39-44.
  2. Miyauchi A, Takamura Y, Ito Y, Miya A, Kobayashi K, Matsuzuka F, et al. 3,5,3'-Triiodothyronine thyrotoxicosis due to increased conversion of administered levothyroxine in patients with massive metastatic follicular thyroid carcinoma. J Clin Endocrinol Metab. 2008;93(6):2239-42.
  3. Abid SA, Stack BC, Bodenner DL. Metastatic Follicular Thyroid Carcinoma Secreting Thyroid Hormone and Radioiodine Avid without Stimulation: A Case Report and Literature Review. Case Rep Endocrinol. 2014;2014:584513.
  4. Karimifar M. A Case of Functional Metastatic Follicular Thyroid Carcinoma that Presented with Hip Fracture and Hypercalcemia. Adv Biomed Res. 2018;7:92.
  5. Gross JL, Vasques Moraes I. Thyroid hormone-producing metastases in differentiated thyroid cancer. J Endocrinol Invest. 1996;19(1):21-4.
  6. Camacho P, Gordon D, Chiefari E, Yong S, DeJong S, Pitale S, et al. A Phe 486 thyrotropin receptor mutation in an autonomously functioning follicular carcinoma that was causing hyperthyroidism. Thyroid. 2000;10(11):1009-12.
  7. Kasagi K, Takeuchi R, Miyamoto S, Misaki T, Inoue D, Shimazu A, et al. Metastatic thyroid cancer presenting as thyrotoxicosis: report of three cases. Clin Endocrinol (Oxf). 1994;40(3):429-34.