What is Thyroid Stunning?
Thyroid stunning is a phenomenon where exposure to radioiodine causes a temporary reduction in the ability of thyroid tissue (whether normal remnant tissue, functioning metastases, or benign thyroid tissue) to trap and uptake subsequent doses of radioiodine, without actual destruction of the thyroid cells. 1, 2
Mechanism and Characteristics
Stunning represents decreased iodide trapping capacity rather than cell death - the effect is transitory and reversible, as evidenced by the re-appearance of uptake capacity months after the initial stunning effect 1
The phenomenon is radiation dose-dependent - the risk and severity of stunning increases progressively with larger radioiodine doses 1, 3
Radiation-induced metabolic suppression is the likely mechanism - exposure to radioiodine causes radiation damage to thyroid follicles, leading to release of thyroid hormones into the bloodstream and temporarily reduced cellular metabolism 4
Stunning involves downregulation of the sodium iodide symporter (NIS) - radiation exposure reduces both iodide transport function and NIS mRNA expression in thyroid cells 5
Clinical Significance by Isotope
I-131 diagnostic doses can cause stunning - the threshold for stunning in thyroid remnants appears to be between 37 MBq and 111 MBq, meaning therapeutic doses of 3.7 GBq (3700 MBq) can definitely cause stunning 1
I-123 causes MORE stunning per unit absorbed dose than I-131 - with a relative biological effectiveness of approximately 5, meaning I-123 is actually more potent at causing stunning despite delivering lower absorbed doses per unit activity 5
Other radionuclides also cause stunning - Tc-99m and At-211 (both transported via NIS) can reduce iodide transport and NIS expression, with At-211 being the most potent per unit absorbed dose 5
Disease-Specific Stunning Effects
The degree of stunning varies significantly by thyroid condition: 3
- Goiter: 21% reduction per Gray of tracer radiation dose - the highest stunning effect
- Multifocal autonomous nodules: 8.2% reduction per Gray - moderate stunning effect
- Disseminated autonomy: significant stunning (p < 0.05)
- Solitary toxic nodules: 1.2% reduction per Gray - minimal stunning effect (not statistically significant)
- Graves' disease: no significant stunning (p > 0.05)
Time Course and Recovery
Onset varies by isotope - NIS downregulation occurs rapidly (<1 day) after I-123 or At-211 exposure, but is delayed after I-131 or Tc-99m exposure 5
Recovery is possible but variable - iodide transport and NIS expression recovered only for At-211 in experimental studies, while other isotopes showed persistent effects 5
Clinical recovery can take months - in the case report of metastatic papillary thyroid cancer, uptake re-appeared 6 months after the initial therapeutic dose that caused stunning 1
Practical Implications for Treatment
Stunning may not affect ablation success rates - studies that recognized stunning did not demonstrate differences in successful first-time ablation outcomes 2
Timing between doses matters - studies that allowed less time between diagnostic and therapy doses, and more time between therapy dose and post-treatment scans (at least 1 week), were less likely to observe stunning 2
Dosimetry should account for stunning - correction factors can be developed to calculate stunning-independent radioiodine activity, particularly for goiter and multifocal autonomous nodules, to achieve desired intra-thyroidal radiation doses 4, 3
Common Pitfall
The major clinical pitfall is assuming I-123 avoids stunning - while many clinics switched from I-131 to I-123 for pre-therapeutic diagnostic imaging to avoid stunning, I-123 actually causes more severe stunning per unit absorbed dose than I-131, with a relative biological effectiveness of about 5 5