Hyperthyroidism secondary to disseminated differentiated thyroid cancer on 99mTcO4 scan

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Hyperthyroidism secondary to disseminated differentiated thyroid cancer on 99mTcO4 scan

Thyroid cancer and hyperthyroidism rarely occur together—but when they do, the source of the overactive thyroid can be unexpected. A 2019 case from Fudan University’s Zhongshan Hospital in Shanghai illustrates how metastatic thyroid cancer can trigger hyperthyroidism and how a common nuclear medicine scan helped diagnose the hidden cause.

The patient, a 53-year-old woman, was admitted to Zhongshan Hospital for right iliac bone pain and a suspected metastasis on CT scan. Eight years earlier, she’d undergone a right thyroid lobectomy, but no cancer was found at the time. In the year before admission, she developed hyperthyroidism—with classic symptoms like weight loss, rapid heartbeat, and anxiety—but couldn’t take the common treatment methimazole because it lowered her white blood cell count. Her lab results confirmed severe overactive thyroid: free triiodothyronine (T3) was 12.3 pmol/L (normal: 2.8–7.1 pmol/L), free thyroxine (T4) was 46.7 pmol/L (normal: 12.0–22.0 pmol/L), and thyroglobulin (Tg)—a protein made by thyroid cells—was sky-high at >5000 ng/mL (normal: 1.4–78 ng/mL). Her thyroid-stimulating hormone (TSH), which regulates thyroid function, was undetectably low (<0.005 mIU/mL; normal: 0.270–4.200 mIU/mL). Ultrasound showed nodules in her left thyroid lobe, suspected to be benign adenomas.

To investigate, doctors used a 99mTcO4 scintigraphy scan—a test that uses a radioactive tracer to map thyroid tissue. The scan showed mild radioactivity in her neck (less than the nasal mucosa, a common reference point) and unexpected lesions in her chest. A whole-body 99mTcO4 scan revealed intense tracer uptake in her chest and multiple bones—signs of possible metastasis. A CT-guided biopsy of the bone lesion found follicular epithelium (the type of cells in thyroid tissue), and immunohistochemistry confirmed the cells were thyroid-derived: they tested positive for thyroglobulin (Tg) and thyroid transcription factor-1 (TTF-1), proteins unique to thyroid cells.

The patient underwent a left thyroid lobectomy. The tissue was diagnosed as a follicular adenoma, a benign tumor. But the widespread chest and bone lesions seen on imaging didn’t fit a benign diagnosis—they pointed to follicular thyroid carcinoma, a type of differentiated thyroid cancer that can spread. Doctors decided to treat her with radioactive iodine (131I), a standard therapy for metastatic differentiated thyroid cancer, at a dose of 3700 MBq (100 mCi). A post-treatment whole-body scan confirmed the lesions were indeed metastases: intense 131I uptake in her chest (lung mets) and bones (bone mets).

The results were dramatic. Four months later, her T3, T4, and Tg levels dropped significantly: T3 to 3.2 pmol/L, T4 to 12.7 pmol/L, and Tg to 430.9 ng/mL. She received a second 131I treatment, and a year later, her thyroid hormone levels were nearly normal (T3: 4.3 pmol/L, T4: 29.1 pmol/L) and her Tg—now a marker for residual cancer—plummeted to 3.2 ng/mL (within the normal range).

This case shines a light on a rare phenomenon: hyperthyroidism caused by metastatic differentiated thyroid cancer. While thyroid cancer and hyperthyroidism can coexist, it’s unusual for the metastasis itself to produce enough thyroid hormone to cause overactive thyroid symptoms. The 99mTcO4 scan was key here: because the residual thyroid tissue took up less tracer than the nasal mucosa (a sign of low thyroid activity), the high Tg and thyroid hormone levels had to come from somewhere else—namely, the metastatic lesions.

99mTcO4 is a substrate for the sodium-iodide symporter (NIS), a protein that lets thyroid cells take up iodine (and similar tracers). It’s widely used in thyroid imaging because it’s safe and provides clear images of thyroid tissue. While it’s less sensitive than 131I for detecting small metastases, it’s still a valuable tool—especially when combined with lab results like elevated Tg.

The takeaway for doctors? If a patient has hyperthyroidism, elevated Tg, and low 99mTcO4 uptake in the residual thyroid (less than the nasal mucosa), metastatic differentiated thyroid cancer should be high on the list of possible causes. This case also shows that even when the primary thyroid tumor is benign (like the follicular adenoma here), widespread metastases can be malignant—and require targeted therapy like radioactive iodine.

The study was led by researchers from the Department of Nuclear Medicine at Zhongshan Hospital, Fudan University; the Shanghai Institute of Medical Imaging; and the Institute of Nuclear Medicine, Fudan University. Yan Hu and Hong-Yan Yin contributed equally to the work. The corresponding author is Dr. Hong-Cheng Shi (shihongcheng163@163.com), from Zhongshan Hospital’s Department of Nuclear Medicine.

This work was supported by the Scientific Research Foundation for Young Doctors of Zhongshan Hospital, Fudan University (grant number 2018ZSQN025). The authors declare no conflicts of interest. The patient provided written informed consent for her case to be published.

References:

  1. Chapman CN, Sziklas JJ, Spencer RP, Bower BF, Rosenberg RJ. Hyperthyroidism with metastatic follicular thyroid carcinoma. J Nucl Med. 1984;25(12):466-468. doi:10.1097/00004728-198412000-00042
  2. Chantadisai M, Kingpetch K. Usefulness of 99mTc-pertechnetate whole body scan with neck and chest SPECT/CT for detection of post-surgical thyroid remnant and metastasis in differentiated thyroid cancer patients. Ann Nucl Med. 2014;28(7):674-682. doi:10.1007/s12149-014-0864-3
  3. Ahn BC. Reinforcing the ability of 99mTcO4 scintigraphy for identifying differentiated thyroid cancer by TSH stimulation. Clin Nucl Med. 2016;41(10):e412-e413. doi:10.1097/RLU.0000000000001285

doi.org/10.1097/CM9.0000000000000462

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