Teaching Case

36-year-old female patient with papillary thyroid carcinoma. Underwent total thyroidectomy with right neck dissection (suspicious neck lymph nodes were seen on pre op sonar) and ablation of residual thyroid tissue with 2960 MBq of I-131. Follow up I-131 whole body scans (WBS) were negative, but thyroglobulin levels remained elevated.

Her diagnostic scan with 74 MBq of I-131 six weeks post-surgery, with a TSH of > 150mIU/l showed focal increased uptake in the neck as shown in figure 1. Six months and one year post therapy scans after ablation with 2960 MBq of I-131 were negative as shown in figures 2 and 3, respectively, however, her Tg levels were elevated (12.9 ug/l). Neck ultrasound (US) done after her one year therapy scan showed a mass on the right side of the thyroid bed, with no calcifications, measuring 15 x 14 mm. FNA of the mass yielded insufficient sample, so an FDG PET/CT scan on TSH suppression was done, which was negative for any metabolically active disease, as shown in figure 5. A repeat FDG PET/CT scan with exogenous TSH stimulation using Thyrogen®, showed avid disease on a right level IIA lymph node. Histology was positive for metastatic papillary thyroid cancer.

Differentiated thyroid cancer (DTC) is the most frequent endocrine cancer, representing 1% of all malignant tumours [1]. After initial surgery and high-dose radioactive iodine 131 (I-131) ablation, follow-up monitoring consists of regular neck ultrasound, WBS with I-131 or I-123, measurements of Tg and Tg antibody. Undetectable levels of Tg are expected after successful treatment. Stimulated Tg [either by thyroxin (T4) withdrawal or recombinant human thyroid stimulating hormone (rhTSH)] is a sensitive marker of both residual and recurrent disease [2]. Although elevated Tg levels may be a normal finding up to 3 years after a normal WBS, it may reflect non iodine-avid recurrence or metastases in a condition referred to as Thyroglobulin-elevated negative Iodine Scintigraphy (TENIS). FDG PET/CT has a role in these patients. A meta-analysis of 17 studies between 1990 and 2008, including a total of 571 patients found an overall sensitivity for PET of 0.835 (95% CI 0.791–0.873) and specificity of 0.843 (95% CI 0.791–0.886) [3]. FDG PET in combination with TSH stimulation is a more sensitive technique in detecting recurrence or residual disease in patients with negative iodine WBS, as TSH stimulation increases the metabolic activity of tumours. A review by Chao et al [4] looked at 7 prospective controlled clinical trials with 168 patients and found that there was a statistically significant difference between PET scans done on suppression and on TSH stimulation. The detection of non-iodine-avid disease with FDG PET/CT is of importance in the management of DTC as the iodine uptake of a tumour is inversely related to its glucose metabolism, and FDG uptake alone, with concomitant loss of iodine uptake is a functional sign of dedifferentiation[5]. This is likely due to a decrease in sodium-iodide symporter expression and an increase in glucose transporter-1 expression. These patients will not benefit from ‘blind’ high dose I-131 treatment, but rather benefit from surgery, as was shown in our patient. In conclusion FDG PET/CT scans for patients with TENIS should be done with TSH stimulation. Patients who have contraindication to hormone withdrawal or those who cannot tolerate the side effects of hypothyroidism should opt for rhTSH during the 18F-FDG PET-CT study.