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Year : 2021  |  Volume : 19  |  Issue : 1  |  Page : 46-49

Papillary thyroid carcinoma with skeletal metastasis: Late presentation of thyroid cold nodule

Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission05-Jun-2020
Date of Decision16-Aug-2020
Date of Acceptance19-Aug-2020
Date of Web Publication13-Jan-2021

Correspondence Address:
Dr. Julie Hephzibah
Department of Nuclear Medicine, Christian Medical College, Vellore - 632 004, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmi.cmi_98_20

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A 60-year-old female presented with complaints of swelling in front of the neck; on evaluation with thyroid uptake, study showed the presence of cold nodule in the right lobe of thyroid. Fine-needle aspiration of the nodule showed benign disease and started on antithyroid medications. The patient was lost to follow-up for 10 years, after which she presented with swelling in the same region of the cold nodule. Due to the continued increase in the size of the swelling, she underwent a fine-needle aspiration biopsy and ultrasound with findings consistent with carcinoma, for which she underwent total thyroidectomy, followed by radiation therapy. On further evaluation for residual thyroid using iodine, whole-body scan showed residual disease with disseminated osseous and lymph node metastases, which was treated twice with 100 mCi of I131, resulting in. A cold nodule on thyroid scan can be benign or malignant and should be kept on regular follow-up and if left untreated may present with disseminated aggressive disease.

Keywords: Iodine-131, papillary thyroid carcinoma, radioactive iodine ablation

How to cite this article:
Vishnu A R, Hephzibah J, Mathew D, Sunny SS. Papillary thyroid carcinoma with skeletal metastasis: Late presentation of thyroid cold nodule. Curr Med Issues 2021;19:46-9

How to cite this URL:
Vishnu A R, Hephzibah J, Mathew D, Sunny SS. Papillary thyroid carcinoma with skeletal metastasis: Late presentation of thyroid cold nodule. Curr Med Issues [serial online] 2021 [cited 2023 Feb 1];19:46-9. Available from: https://www.cmijournal.org/text.asp?2021/19/1/46/306940

  Introduction Top

Thyroid nodules can be visualized by inspection or identified during palpation and can be further assessed anatomically by ultrasound and functionally by biochemical investigations such as thyroid function tests and thyroid uptake study (TUS).[1] TUS shows the presence of functioning tissue present in thyroid gland. It can either be “hot” indicating the presence of hyperfunctioning thyroid tissue, which most likely be a benign lesion or “cold,” indicating a nonspecific finding[2] and may be the result of various pathologies,[3] 75% of which is due to a benign pathology.[1] Remaining 25% might be malignant, which requires further investigations and treatment with total thyroidectomy (TT)[4] followed by ablation of the residual tissue, if any by radioactive iodine. Papillary thyroid carcinoma (PTC) is the most common among thyroid cancer, which accounts for about 90% of all cases and has the ability to concentrate iodine, which makes it ideal for treatment with radioiodine[5] for the metastasis to cervical lymph nodes, bones, and lungs. They are usually treated with various doses of radioiodine ranging from 3.7 to 7.4 GBq or more.[6]

  Case Report Top

A 60-year-old female initially presented to her endocrinologist with a chief complaint of midline swelling in the neck in 2004. On evaluation, she was diagnosed to have Graves' disease, for which she was on medications from 2004 to 2007.

In 2004, her thyroid-stimulating hormone was 0.11 mIU/L, total T4 was 8.6 ng/dl, and free T4 was 1.05 ng/dl. She had undergone a TUS-suspecting hyperthyroidism. Radionuclide scan showed the presence of nonfunctioning cold nodule [Figure 1] occupying the lower pole of the right lobe with radioactive iodine uptake values of 6%, 11%, and 17% at 2, 6, and 24 h, respectively. On the basis of the presence of cold nodule, she was subjected to fine-needle aspiration cytology (FNAC), which showed benign lesion. On the basis of cold nodule in TUS and benign lesion from FNA, she was kept on follow-up by her treating endocrinologist. She was on regular follow-up with thyroid function test until 2007, after which she was lost to follow-up. In 2017 at the age of 73, she presented with complaints of sudden increase in size of the swelling. This was associated with complaints of persistent cough and dyspnea.
Figure 1: Thyroid uptake study done in 2004 showing cold nodule in the right lobe of thyroid (in between blue arrows).

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On examination, the swelling in front of the neck was found to be multilobulated, firm in consistency in the right lobe of thyroid. Repeat FNAC of the swelling revealed the presence of malignant lesion from the same “cold” nodule, which was benign 13 years ago. Preoperative ultrasonography findings showed a hard-fixed mass in the right lobe of thyroid, which was seen infiltrating the internal jugular vein (IJV) and with no significant neck nodes.[5] Hence, she was planned for TT along with IJV excision. Intraoperatively, there was a hard-fixed mass involving the right lobe infiltrating the strap muscle, trachea, and tracheoesophageal groove. Histopathology was reported as a follicular variant of PTC with a focus of poorly differentiated component in the right lobe, staging of the disease being pT4N0.

She was planned for intensity-modulated radiation therapy in view of poorly differentiated component, infiltration of IJV by the tumor, and gross tumor left in the thyroid bed postsurgery.[7] She received 64 Gy in thirty fractions to the thyroid bed. This was followed by iodine 131 scan, which showed tracer uptake in the thyroid bed and adjacent regions indicative of residual thyroid with nodal metastases. In addition, there were iodine-avid lesions in multiple bones involving skull and pelvic bones, indicating bone metastases [Figure 2]. Her stimulated serum thyroglobulin was 1049. She underwent radioactive iodine ablation twice with a dose of 3700 MBq each, following which her residual lesion was ablated, and osseous metastasis had slowly regressed, which was evident from the follow-up scan done every 6 months. Her serial stimulated serum thyroglobulin values had significantly reduced (1049 in January 2018 423 in November 2018 394 in November 2019).
Figure 2: Iodine 1-131 Whole body scan Anterior and posterior views: a) Pretherapy scan in April 2018 - Iodine avid lesions in thyroid bed and multiple bones suggestive of bulky thyroid residual with osseous metastases, Serum Tg was 1049ng/ml. b) Follow up scan In November 2018 showed complete regression of residual and persistent uptake in skeletal metastases. Serum Tg was 423ng/ml). c) Follow up scans in April 2019 and d) in November 2019 showed decrease in the iodine avid osseous metastases after two doses of I131 ablation

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  Discussion Top

Solitary thyroid nodule is defined as a discrete lesion within the thyroid gland, radiologically distinct from surrounding thyroid parenchyma.[5] It is more common among females and in age more than 60 years.[8] Close follow-up is suggested for solitary cold nodule compared to multinodular goiter as the incidence of PTC is relatively higher as in this case.[9] FNA of the cold nodule before surgery is warranted.[10] Radioactive iodine treatment is an important radiopharmaceutical agent in nuclear medicine practice for the treatment of hyperthyroidism and differentiated thyroid cancer.[11] I131 of about 3.7–5.5 MBq/g of thyroid tissue corrected for the 24 h 131I uptake is recommended,[12] and intent is to either partially or completely ablate the thyroid gland.

Differentiated thyroid carcinoma can present with bone metastases in its early stage,[13] with the incidence of about 2%–13%.[14] Bone metastasis treated with I131 had a longer survival rate.[11] Ramadan et al. suggested that, in young patients, multiple doses of I131 can be given with a cumulative dose of up to a total dose of 600 mCi for a curative intent,[15] and in age more than 60 years, palliative intent should be considered.[16] Rubino et al. suggested that side effects of bone marrow toxicity and secondary malignancy are caused due to increased I131 dose of 200 mCi.[17] Durante et al. have suggested that I131 can be given until iodine-avid lesions are present, dose not exceeding 600 mCi.[15] When extensive osseous metastases are found, radiation exposure to the bone marrow should be <200cGy, and this can be achieved by giving 100 mCi of I131 every 6 months to decrease the toxicity. In our patient following three radioiodine therapies administered 6–9 months apart, there was significant regression of metastases as confirmed with imaging and biochemical response.

  Conclusion Top

  • A cold nodule on thyroid scan can be benign or malignant and should be on regular follow-up and if left untreated may present with metastatic thyroid cancer
  • Differentiated thyroid carcinoma can present with bone metastases at any stage and radioactive I131 ablation should be included as an adjuvant therapy
  • A dose of 100 mCi I131 in multiple frequencies at 6 monthly intervals can be used to treat iodine-avid bone metastases from differentiated thyroid cancers.

Informed consent

Informed written consent was obtained from the patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Durski JM, Bogsrud TV. Nuclear Medicine in Evaluation and Therapy of Nodular Thyroid. Thyroid Nodules: Diagnosis and Management. In Gharib H: (eds) Thyroid Nodules contemporary endocrinology. p.p 35-62. Humana press, cham. https://doi.org/10.1007/978-3-313-59474-34.  Back to cited text no. 1
Dohán O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, et al. The sodium/iodide symporter (NIS): Characterization, regulation, and medical significance. Endocr Rev 2003;24:48-77.  Back to cited text no. 2
Tonacchera M, Viacava P, Agretti P, de Marco G, Perri A, di Cosmo C, et al. Benign nonfunctioning thyroid adenomas are characterized by a defective targeting to cell membrane or a reduced expression of the sodium iodide symporter protein. J Clin Endocrinol Metab 2002;87:352-7.  Back to cited text no. 3
Papini E, Gugliemi R, Pacella CM. Laser, radiofrequency, and ethanol ablation for the management of thyroid nodules. Curr Opin Endocrinol Diabetes Obes 2016;23:400-6.  Back to cited text no. 4
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1-33.  Back to cited text no. 5
Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2008;35:1941-59.  Back to cited text no. 6
Kiess AP, Agrawal N, Brierley JD, Duvvuri U, Ferris RL, Genden E, et al. External-beam radiotherapy for differentiated thyroid cancer locoregional control: A statement of the American Head and Neck Society. Head Neck 2016;38:493-8.  Back to cited text no. 7
Belfiore A, La Rosa GL, La Porta GA, Giuffrida D, Milazzo G, Lupo L, et al. Cancer risk in patients with cold thyroid nodules: Relevance of iodine intake, sex, age, and multinodularity. Am J Med 1992;93:363-9.  Back to cited text no. 8
McCall A, Jarosz H, Lawrence AM, Paloyan E. The incidence of thyroid carcinoma in solitary cold nodules and in multinodular goiters. Surgery 1986;100:1128-32.  Back to cited text no. 9
La Rosa GL, Belfiore A, Giuffrida D, Sicurella C, Ippolito O, Russo G, et al. Evaluation of the fine needle aspiration biopsy in the preoperative selection of cold thyroid nodules. Cancer 1991;67:2137-41.  Back to cited text no. 10
Schlumberger M, Challeton C, De Vathaire F, Travagli JP, Gardet P, Lumbroso JD, et al. Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma. J Nucl Med 1996;37:598-605.  Back to cited text no. 11
Giovanella L, Avram AM, Iakovou I, Kwak J, Lawson SA, Lulaj E, et al. EANM practice guideline/SNMMI procedure standard for RAIU and thyroid scintigraphy. Eur J Nucl Med Mol Imaging 2019;46:2514-25.  Back to cited text no. 12
Wu K, Hou SM, Huang TS, Yang RS. Thyroid carcinoma with bone metastases: A prognostic factor study. Clin Med Oncol 2008;2:129-34.  Back to cited text no. 13
Fanchiang JK, Lin JD, Huang MJ, Shih HN. Papillary and follicular thyroid carcinomas with bone metastases: A series of 39 cases during a period of 18 years. Changgeng Yi Xue Za Zhi 1998;21:377-82.  Back to cited text no. 14
Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 2006;91:2892-9.  Back to cited text no. 15
Ramadan S, Ugas MA, Berwick RJ, Notay M, Cho H, Jerjes W, et al. Spinal metastasis in thyroid cancer. Head Neck Oncol 2012;4:39.  Back to cited text no. 16
Rubino C, Adjadj E, Doyon F, Shamsaldin A, Abbas TM, Caillou B, et al. Radiation exposure and familial aggregation of cancers as risk factors for colorectal cancer after radioiodine treatment for thyroid carcinoma. Int J Radiat Oncol Biol Phys 2005;62:1084-9.  Back to cited text no. 17


  [Figure 1], [Figure 2]


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