Radioiodine treatment of hyperthyroidism is an elegant exploitation of a pathophysiological process for safe and effective noninvasive treatment of disease. A dose(Gy)-response relationship clearly exists for I-131 therapy in hyperthyroidism. However, despite a good understanding of disease pathophysiology and well-described methods of personalized predictive prescription, the implementation of I-131 theranostics in everyday practice is usually limited by the lack of time, cost or expertise. To strike a balance between clinical outcomes versus resource-demanding theranostic prescription, current practice is usually empiric prescription modified by simple parameters such as gland size (measured or estimated), Tc-99m pertechnetate uptake, thyroid function biochemistry, treatment intent, and clinical Gestalt.[10–14]
Since our institution has I-131 theranostic capability for metastatic differentiated thyroid cancer, we embarked on this internal quality assurance audit to address whether it is clinically justified for us to continue with traditional empiric prescription for hyperthyroid disease? Our results seem to support continuing with empiric prescription for most, but not all hyperthyroid patients, evident by a very good overall remission rate of 80.8%. Dosimetric subanalysis of Graves' disease suggests better treatment success with a thyroid mean absorbed dose >200 Gy (75% of Graves' disease patients), than lower. Our results are also very similar to that by Taprogge et al., who observed by meta-analyses that 200 Gy rendered 81% of Graves' disease patients non-hyperthyroid.
Our Graves' disease patients were prescribed a wider range of activities as compared to toxic adenoma or multinodular goitre. Not surprisingly, Graves' disease patients who were prescribed lower activities were more likely to have persistent hyperthyroidism. Further analysis revealed an interesting trend within our department toward prescribing lower activities in Graves' disease with higher Tc-99m pertechnetate uptake. Indeed, delving into individual cases of very high (>15%) Tc-99m pertechnetate uptake revealed below-average activity prescription and a high rate of persistent hyperthyroidism. This observation could reflect a general hesitance to prescribe a "standard" I-131 activity in patients with significant Graves' hyperactivity. This might be explained by a wariness of precipitating radiation-induced thyroiditis or thyroid storm in patients with very active Graves' disease.
The literature suggests, however, that the rate of I-131 induced thyroiditis and thyroid storm is low and can be mitigated by judicious coverage with beta-blockade and corticosteroids.[3,15,16] This approach should be particularly considered in older patients with cardiovascular comorbidities. Furthermore, the low risk of significant radioiodine-induced flare must be balanced with the real consequences of uncontrolled hyperthyroidism, especially in women planning pregnancy and medically frail patients. Additionally, in their examination of the nonlinear relationship of 20-min Tc-99m pertechnetate uptake and 24-hour radioiodine uptake (RAIU) in euthyroid patients with Graves' disease, Szumowski et al. showed that beyond a 20-min Tc-99m pertechnetate uptake of approximately 10%, the corresponding RAIU appears to plateau. This means that deliberate empiric reduction of the prescribed I-131 activity in a patient with significant thyroid hyperactivity might be counter-productive in terms of the perceived risk of flare versus risk of persistent hyperthyroidism. Perhaps it is in the subset of patients with Graves' disease and very high Tc-99m pertechnetate uptake that a theranostically guided prescription, such as the methods described by the EANM Therapy Committee, should be sought to ensure resolution of hyperthyroidism by delivering >300 Gy to the thyroid.[4,9] The dosimetric concept of "fractionating" I-131 over two or more treatments to mitigate any perceived risk of radiation-induced thyroid crisis should also be explored in future studies.
For multinodular goitre, we found that our prescribed I-131 activities for remission vs persistently hyperthyroid groups were essentially the same (444-481MBq; 12–13 mCi). However, we observed that the persistently hyperthyroid group had significantly higher Tc-99m pertechnetate uptake (7.3 ± 3.9%) as compared with the remission group (2.8 ± 3.0%; p = .014). There are multiple possible explanations for this, including reduced I-131 Residence Times in very active disease or larger gland sizes in those patients.[16,17] The implication for our local practice is that we should prescribe higher I-131 activities for multinodular goitres with high Tc-99m pertechnetate uptake to improve the chances of remission.
For toxic adenoma, the vast majority (90%) of our patients achieved remission using 444MBq (12 mCi). From a dosimetric perspective, this high success rate could be explained by the higher I-131 avidity (i.e., radioconcentration) of a toxic nodule in relation to the rest of the normal thyroid parenchyma. It would therefore be relatively easier per administered activity for a solitary toxic nodule to achieve the absorbed dose (Gy) threshold for remission as compared to multinodular goitre.
While this study has general limitations associated with a retrospective, single-centre clinical audit, including our limited and heterogenous study population, the success of treatment and prescribing patterns demonstrated here are in keeping with those reported both nationally and internationally which improves the potential generalizability of our findings.[10,11,18,19] An additional limitation inherent in the retrospective nature of the study was absence of follow-up data for 83 of the 229 patients treated by our institution over the 5-year period, limiting our analysis to a subset. There was also lack of patient-specific data regarding the contribution of gland mass to treatment success, particularly in Graves' disease and multinodular goiter. This does not, however, diminish the relevance of the observation that adequate activity must be prescribed to successfully treat hyperthyroidism. Additionally the lower end of the follow-up time (0.9 months) included patients with hypothyroidism who might have being only transiently rendered hypothyroid before rebounding, though the incidence of this is low. Finally, the proportion of patients successfully treated might have been underestimated due to lack of available follow-up beyond 4.4 months for some of the patients who remained hyperthyroid.
Clin Endocrinol. 2022;97(1):124-129. © 2022 Blackwell Publishing