Correction for hyperfunctioning radiation-induced stunning (CHRIS) in benign thyroid diseases

Abstract

Purpose: Radioiodine-131 treatment has been a well-established therapy for benign thyroid diseases for more than 75 years. However, the physiological reasons of the so-called stunning phenomenon, defined as a reduced radioiodine uptake after previous diagnostic radioiodine administration, are still discussed controversially. In a recent study, a significant dependence of thyroid stunning on the pre-therapeutically administered radiation dose could be demonstrated in patients with goiter and multifocal autonomous nodules. A release of thyroid hormones to the blood due to radiation-induced destruction of thyroid follicles leading to a temporarily reduced cell metabolism was postulated as possible reason for this indication-specific stunning effect. Therefore, the aim of this study was to develop dose-dependent correction factors to account for stunning and thereby improve precision of radioiodine treatment in these indications.

Methods: A retrospective analysis of 313 patients (135 with goiter and 178 with multifocal autonomous nodules), who underwent radioiodine uptake testing and radioiodine treatment, was performed. The previously determined indication-specific values for stunning of 8.2% per Gray in patients with multifocal autonomous nodules and 21% per Gray in patients with goiter were used to modify the Marinelli equation by the calculation of correction factors for hyperfunctioning radiation-induced stunning (CHRIS). Subsequently, the calculation of the required activity of radioiodine-131 to obtain an intra-therapeutic target dose of 150 Gy was re-evaluated in all patients. Furthermore, a calculation of the hypothetically received target dose by using the CHRIS-calculated values was performed and compared with the received target doses.

Results: After integrating the previously obtained results for stunning, CHRIS-modified Marinelli equations could be developed for goiter and multifocal autonomous nodules. For patients with goiter, the mean value of administered doses calculated with CHRIS was 149 Gy and did not differ from the calculation with the conventional Marinelli equation of 152 Gy with statistical significance (p = 0.60). However, the statistical comparison revealed a highly significant improvement (p < 0.000001) of the fluctuation range of the results received with CHRIS. Similar results were obtained in the subgroup of patients with multifocal autonomous nodules. The mean value of the administered dose calculated with the conventional Marinelli equation was 131 Gy and therefore significantly below the CHRIS-calculated radiation dose of 150 Gy (p < 0.05). Again, the fluctuation range of the CHRIS-calculated radiation dose in the target volume was significantly improved compared with the conventional Marinelli equation (p < 0.000001).

Conclusions: With the presented CHRIS equation it is possible to calculate a required individual stunning-independent radioiodine activity for the first time by only using data from the radioiodine uptake testing. The results of this study deepen our understanding of thyroid stunning in benign thyroid diseases and improve precision of dosimetry in radioiodine-131 therapy of goiter and multifocal autonomous nodules.

Keywords: Benign thyroid disease; CHRIS; Radioiodine therapy; Stunning; Thyroid.