Recombinant Human Thyroid-Stimulating Hormone Versus Thyroid Hormone Withdrawal in the Identification of Metastasis in Differentiated Thyroid Cancer with ¹³¹I Planar Whole-Body Imaging and ¹²⁴I PET

DISCUSSION

This study reports the largest series of patients who have undergone evaluation for lesion detection of metastatic DTC after preparation with either THW or rhTSH with both ¹³¹I planar WB images and ¹²⁴I PET.

Our prospective study strongly suggests that more metastatic foci of DTC were detected on radioiodine scans after preparation with THW than with rhTSH injections. Furthermore, ¹²⁴I PET scans detected more foci than did ¹³¹I planar WB scans.

Driedger et al. (6), Taïeb et al. (7), and Hung et al. (8) have published case reports (2, 1, and 1 patients, respectively) in which preparation with THW was compared with rhTSH. THW appeared superior in the detection of metastatic foci in all 4 of these patients. Potzi et al. (5) evaluated 4 patients who underwent scanning after preparation with both THW and rhTSH, and again THW was superior to rhTSH.

In comparing our data with other reports that evaluated preparation with THW and rhTSH, our data are most consistent with those of Freudenberg et al. (4) but not consistent with the data of Klubo-Gwiezdinska et al. (11) or Tala et al. (12). In the study of Freudenberg et al. (4), their endpoint was the estimation of the radiation absorbed dose to the metastatic foci after THW and rhTSH preparation. They reported that the mean radiation absorbed dose for the lesions identified in a group of patients (n = 27) prepared with rhTSH was only 60% of the radiation absorbed dose to lesions in another group of patients (n = 36) prepared with THW. However, this difference was not statistically different. Klubo-Gwiezdinska et al. (11) from our institution evaluated patient outcomes from the ¹³¹I therapy as their endpoint for comparison. They reported that patients who had metastatic DTC achieved comparable benefit from their ¹³¹I treatment whether prepared with rhTSH or THW. Likewise, Tala et al. (12) were unable to demonstrate any difference in the 5-y survival of patients with distant metastases who were prepared with injections of rhTSH relative to those patients prepared with THW. At this time, we cannot explain the difference between the results of the present study, other imaging studies (5–8), and the study of Freudenberg et al. (4) versus the outcome studies of Klubo et al. (11) and Tala et al. (12). However, the latter were both retrospective studies with a relative short duration of follow-up, and these studies were not noninferiority studies. Thus, an absence of evidence that there was a difference is not evidence that the outcomes are the same. Another possible explanation is that although the preparation with THW relative to rhTSH injections may result in the superior uptake of ¹³¹I and ¹²⁴I for lesion detection and even in a high radiation absorbed dose, the difference in uptake does not result in a difference in radiation absorbed dose to the metastases and thus in a different therapeutic effect. Further controlled prospective noninferiority studies are warranted.

Our study has several potential limitations. First, although this was a prospective study, our patients were not randomized as to the method of preparation. This decision was made by the referring endocrinologist, whose criteria were subjective and not systematically recorded. Accordingly, there may have been a bias between the 2 groups. However, there was no statistical difference between the 2 groups regarding age, sex, thyroglobulin level, urine iodine level, type of histology, or indications on the order form. A prospective study in which each patient is studied using both methods of preparation is warranted.

Another limitation of our study is that we included in our analysis foci of uptake in the thyroid bed. Although these foci were most likely locoregional disease, one cannot completely exclude normal remnant tissue that had not been successfully ablated. However, we believe the inclusion of these foci was appropriate because all patients had prior ¹³¹I ablation, and 35 of 40 patients had at least 2 prior treatments with ¹³¹I. Thus, any radioiodine activity in the thyroid bed more than likely represented local regional disease and not untreated normal functioning thyroid remnant tissue. Second, the total mean prescribed activity was 18.6 and 19.9 GBq (504 and 539 mCi) in the THW and rhTSH groups, respectively. Finally, on the basis of previous publications (1), the detection of normal functioning thyroid remnant tissue after preparation with rhTSH was comparable to that after preparation of THW, and thus the inclusion of foci in the thyroid bed area that were in fact normal functioning thyroid remnant tissue would bias the results toward the 2 preparations being equal—not different. Thus, exclusion of any true normal functioning thyroid remnant tissue would most likely accentuate the differences between the 2 methods of preparation.

Nevertheless, why should the detection of metastases after preparation with THW be superior to the preparation with rhTSH? This has not yet been determined. However, as Zanotti-Fregonara et al. (3) have noted, the function of normal thyroid tissue may be biologically distinct from that of metastases, and metastases may have reduced ability to take up iodine. Of course, this is why thyroid cancer typically appears hypofunctioning in an otherwise normal thyroid gland. Because of this reduced ability to take up iodine, metastases may require a more prolonged period of TSH stimulation of the sodium-iodide symporter, and preparation with THW may provide a longer and more profound period of TSH stimulation of the sodium-iodide symporter than would 2 injections of rhTSH. Because of the longer period of TSH stimulation, THW could result in greater uptake in the foci and thus better detection and potentially greater radiation absorbed dose to the tumor per gigabecquerel (mCi) of ¹³¹I administered (3).