Nine RCTs (total n=596; 301 intervention participants, 175 placebo control participants and 120 'no treatment' control participants) were included.
Nodule volume.
L-T4 treatment resulted in a mean change in nodule volume of 0.2 mL (range: -1.4 to 1.3). In the control group nodules changed in volume by 0 mL (range: -2 to 0.8).
Nodule size.
L-T4 treatment resulted in a mean change in maximal module diameter of 0.5 cm (range: -1.7 to 0.1). In the control group, the maximal module diameter changed by 0.4 cm (range: -1.8 to 0.1).
Hormone levels.
T4 and TSH levels changed significantly in almost all of the studies after TSH suppression therapy: the mean changes in T4 and TSH levels were 46.1 nmol/L, (range: 25.7 to 64.6) and 1.1 mU/L (range: -2 to 0.79), respectively. Hormone levels did not change significantly in the control group: the mean changes in T4 and TSH levels were 1.9 nmol/L (range: -7.7 to 2) and 0 mU/L (range: -0.4 to 0.15), respectively.
Changes in nodule size.
Thirty-nine of the 180 patients in the L-T4 group and 18 of the 178 patients in the control group showed a reduction in nodule volume that was greater than or equal to 50%. The random-effects model gave a pooled RR of 1.83 (95% confidence interval, CI: 0.90, 3.73), while the fixed-effect model gave an RR of 2.1 (95% CI: 1.27, 3.57). There was no significant heterogeneity between the studies. The pooled estimate was also robust to the choice of placebo or no treatment for the control group (pooled non significant RR 1.93, 95% CI: 0.67, 5.48), regardless of the choice of meta-analysis model.
In the 6 studies that reported the proportion of patients that experienced nodule growth, 59 of the 237 patients who received thyroid hormone and 89 of the 234 patients in the control group exhibited nodule growth. Pooling using the random-effects model gave a pooled RR of 0.66 (95% CI: 0.51, 0.86) indicating that L-T4 significantly inhibited nodule growth. However, the chi-squared statistic indicated significant heterogeneity between the studies.
Adverse effects of TSH suppression therapy.
One of the 9 studies reported a significant weight reduction of 1.6 kg following L-T4 therapy, compared with an increase of 0.2 kg after placebo therapy. Another study reported a high incidence of tachycardia (16%) after treatment with L-T4.