8. Haugen BR, Pacini F, Reiners C, et al. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab. 1999;84:3877–3885. Frederik A. Verburg* Markus Dietlein Lutz Freudenberg Sophie Leboulleux Fabian Pitoia Christoph Reiners Marcel Stokkel Markus Luster *University Hospital Aachen Pauwelsstrasse 30 52074 Aachen, Germany E-mail: fverburg@ukaachen.de Published online Aug. 30, 2012. DOI: 10.2967/jnumed.112.108738 REPLY: We always welcome a professional dialogue from esteemed colleagues in regard to studies that we have published, and we believe that such a dialogue helps us all move forward to a more accurate understanding of the world about us. Continuing in that spirit, I would like to address the various comments in the letter to the editor from Verburg et al. regarding our report comparing the number of metastatic lesions of differentiated thyroid cancer (DTC) detected after preparation with thyroid hormone withdrawal (THW) versus injections of recombinant thyroid-stimulating hormone (rhTSH) (1). Our understanding of the main point of their letter is that they believe that our recommendation regarding selective use of rhTSH is too strong and that they would like to see a more “nuanced” view on the data presented. Our recommendation was that, until more data become available, physicians should be cautious in using rhTSH for patient preparation before diagnostic scanning for the detection of DTC or treatment of distant metastases secondary to DTC with 131 I. Insofar as the data support this recommendation, it would not appear appro- priate to characterize the recommendation as being too strong. When data are clear-cut, there is less accommodation for “nuance.” With regard to the observation of Verburg et al. that our entire study appeared methodologically geared toward comparing 131 I with 124 I—indeed, the data were obtained from our previously published original study (2) comparing 131 I planar imaging with 124 I PET, with 16 additional patients studied and included. However, whether the data were derived from a study comparing lesion detection of 131 I planar imaging with 124 I PET is not in and of itself a limitation. Although there were limitations to our study that we recognized and discussed in the publication, we do not believe this is one of them. With regard to the interest of Verburg et al. in seeing further statistical analyses comparing the 2 radioisotopes, especially if we additionally had acquired and evaluated 131 I SPECT/CT, we noted in our original publication ( 2) that a comparison of 131 I SPECT/CT with 124 I PET would have been valuable for that study. However, such a comparison was not critical to the present study ( 1) because we were comparing planar imaging with planar imaging and PET with PET. To address Verburg et al.’s further opinion that we analyzed differences between rhTSH and THW instead of comparing lesion detection on 131 I planar imaging versus 124 I PET, we did not perform evaluations after rhTSH and THW instead of lesion detection but in addition to lesion detection. Verburg et al. subsequently state that they were surprised we did not use 124 I-PET to perform dosimetry for our patients. They believe this would have been clinically relevant, especially in patients with metastatic lesions, because visualization of metastases does not au- tomatically indicate the possibility of an effective 131 I treatment. Several important facts will help clarify this issue. First, the calcu- lated radiation absorbed dose to a focal lesion or organ as determined by the various methods of 124 I dosimetry does not necessarily cor- relate with clinical outcomes or side effects (3,4). However, we do agree that lesional dosimetry should be performed—not necessarily to indicate clinical relevance based on a calculated radiation absorbed dose but rather to indicate clinical relevance based on a comparison of relative lesional radiopharmacokinetics. We have such a study already under way, as well as another study comparing 124 I dosimetry after preparation with THW and rhTSH injections in patients serving as their own controls. Nevertheless, because clinical outcomes are more important as an endpoint than the calculated radiation absorbed dose by 124 I dosimetry, our paper (1) referred to work from our institution by Klubo-Gwiezdzinska et al., who demonstrated no difference in outcomes when patients with meta- static DTC were prepared for 131 I treatment with either rhTSH or THW (5). Although THW scans may allow better detection of met- astatic lesions than do rhTSH scans, preparation with THW may not necessarily result in significantly more radiation absorbed dose to the metastases than does preparation with rhTSH, thereby not improving outcomes. Thus, the caveat implied by Verburg et al. in regard to the lack of lesional dosimetry using 124 I does not mitigate the fact that more lesions were detected after preparation with THW versus rhTSH injections and that—as concluded in our paper—until more data become available, physicians should be cautious in using rhTSH for patient preparation before diagnostic scanning for the detection of DTC or treatment of distant metastases secondary to DTC with 131 I. In drawing attention to methodology-based drawbacks in our interpretation of the presented data, Verburg et al. are simply repeating limitations of our study that we already noted in our discussion. Next, Verburg et al. note that our statement that our result was most consistent with the data of Freudenberg et al. did not reflect the fact that the conclusion of Freudenberg et al. was more cautious. Our actual statement was, “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. (6)... .In the study of Freudenberg et al. (6), 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 5 27) prepared with rhTSH was only 60% of the radiation absorbed dose to lesions in another group of patients ( n 5 36) prepared with THW. However, this difference was not statistically different.” I will leave the judgment to the reader regarding whether our statement reflected the data and conclusion of Freudenberg et al. and whether our data are most consistent with their data. Interestingly, Verburg et al. reference an article by Haugen et al. (7) as evidence that patient preparation with rhTSH injections has already been shown to be equivalent to patient preparation with THW. However, Verburg et al. do not point out the limitations of the study by Haugen et al. Notably, Haugen et al. reported that THW scans were superior to rhTSH scans in 16% (8/49) of patients, albeit not to a statistically significant extent (P 5 0.109). Second, although Verburg et al. state that this information was crucial for the approval of rhTSH (Thyrogen; Genzyme Corp.) by the Food and Drug Administration, it has not approved Thyrogen for use in met- astatic DTC in the United States, which is stated in the drug insert. Third, the order of THW and rhTSH scans was not randomized; all rhTSH scans were performed first. Although Haugen et al. recog- 1816 THE JOURNAL OF NUCLEAR MEDICINE • Vol. 53 • No. 11 • November 2012 by on May 31, 2020. For personal use only. jnm.snmjournals.org Downloaded from