Optimizing ¹³¹I Uptake After rhTSH Stimulation in Patients with Nontoxic Multinodular Goiter: Evidence from a Prospective, Randomized, Double-Blind Study

Abstract

Prestimulation with recombinant human thyroid-stimulating hormone (rhTSH) augments radioiodine 131 I therapy for benign nontoxic multinodular goiter. The purpose of this study was to determine the optimal time interval between rhTSH and 131 I administration to enhance thyroid radioactive iodine uptake (RAIU). Methods: Patients were randomized, in a 2-factorial design, to receive either a 0.1-mg dose of rhTSH (n 5 60) or placebo (n 5 30) and to a time interval of 24, 48, or 72 h before 131 I administration. The rhTSH-or placebo-stimulated RAIU study was performed at 4 wk after a baseline RAIU assessment in a tertiary referral center at a university hospital. A total of 90 patients (78 women; median age, 52 y; range, 22-83 y) referred to 131 I therapy for symptomatic nontoxic goiter (median goiter volume, 63 mL; range, 25-464 mL) were included in the study. Change in thyroid RAIU was determined at 24 and 96 h after 131 I tracer administration. Results: In the placebo subgroups, RAIU did not change significantly from baseline. The mean (6SE) 24-h RAIU increased from 33.8% 6 2.3% to 66.0% 6 1.8% (111.2% increase) with a 24-h interval, from 36.8% 6 2.1% to 64.6% 6 2.7% (83.3% increase) with a 48-h interval, and from 33.0% 6 2.7% to 49.6% 6 2.5% (62.4% increase) with a 72-h interval. All within-group changes were highly significant (P , 0.001). The effect was negatively correlated with initial RAIU (r 5 20.703, P , 0.001). The increase in 24-and 96-h RAIU was significantly higher in the rhTSH/24-h group than it was in the rhTSH/72-h group (P 5 0.023 and 0.012, respectively) and insignificantly higher than in the rhTSH/48-h group (P 5 0.37 and 0.26, respectively). Conclusion: The effect of rhTSH on thyroid RAIU is most pronounced when administered 24 h before 131 I administration and declines with longer time intervals. Whether there is a similar time dependency for goiter reduction after rhTSH-stimulated 131 I-therapy remains to be clarified.

Non-surgical approach to the benign nodular goiter: new opportunities by recombinant human TSH-stimulated 131I-therapy

“…With lower doses the effect seems to decline but data are conflicting [50]. Importantly, the increase in the thyroid RAIU is inversely correlated to the initial RAIU [50][51][52]56], as shown in Fig. 1, and this implies that rhTSH stimulation is most beneficial in patients with multinodular nontoxic goiter, in whom conventional 131 I-therapy would not be an option due to a low thyroid RAIU.…”

“…rhTSH stimulation reverses this, since the increase in the RAIU in relatively cold areas has been observed to be significantly higher [55]. Accordingly, patients with subclinical hyperthyroidism seem to obtain a more pronounced increase in the RAIU than goiter patients without nodular autonomy [56]. Theoretically, the goiter reduction following rhTSH-stimulated 131 I-therapy should therefore be most effective in patients with subclinical hyperthyroidism, reflected by a low-serum TSH at baseline.…”

Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter

“…The use of LT4 is impossible due to comorbidities and the administration of I-131 becomes a method of choice. Thyroid scintigraphy in patients over the age of 60 often shows low RAIU values accompanying large goiters [15,17,[24][25][26]. Consequently, a single administration of a maximum dose usually does not result in the desired outcomes and the treatment requires the administration of consecutive doses of I-131, which prolongs the duration of the therapy and has a negative influence on the satisfaction with the treatment.…”

“…However, excessive activation of the remaining thyroid tissue may result in the stimulation of hormone production and release, thus inducing hyperthyroidism and leading to the occurrence of a number of symptoms. So far, a dose of rhTSH effective before RIT and safe in patients with a preserved enlarged thyroid has not been determined [15][16][17].…”

THERAPY OF ENDOCRINE DISEASE: Recombinant human TSH and radioactive iodine therapy in the management of benign multinodular goiter

“…Pretreatment with methimazole before 131 I therapy for TMNG is indicated in patients who are at an increased risk for complications due to worsening of hyperthyroidism, including elderly and those with cardiovascular disease or severe hyperthyroidism (35). rhTSH can at least double thyroid RAIU (12,18,36,37,38), depending on the baseline RAIU, and it determines a more homogeneous distribution of 131 I in MNG (22). During the last decade, and based on the above observations, rhTSH has been evaluated as an adjuvant to 131 I therapy, in an attempt to improve the efficacy of this treatment for MNG (18,39,40).…”