1. INTRODUCTION
131I therapy (RIT) has been accepted as a well-established and effective treatment for Graves’ hyperthyroidism (GD). Effectiveness of radioiodine depends on several factors, including course of disease, dosages of 131I, radiosensitivity and goiter volume, as well as retention volume of 131I in the thyroid gland, its effective half-life and previous treatment with antithyroid drugs (ATD). Lithium carbonate blocks the release of organic iodine and thyroid hormone from the thyroid gland without affecting thyroidal active iodine uptake. Accordingly, it is a doubt whether the short-term addition of lithium carbonate, before and after RIT, could prevent the short deterioration of hyperthyroidism and improve therapeutic effect in patients with GD. To address this question, we performed a randomized controlled study to evaluate the addition of lithium carbonate to RIT therapy.
2. SUBJECTS AND METHODS
2.1. Study Groups
During the period from October 2010 to July 2012, we enrolled 100 sequential GD patients with RIT treated for the first time in our department. The age of 29 females ranged from 17 to 62 years (mean 37.5 years), and the age of 71 females ranged from 10 to 53 years (mean 29.7 years). Random allocation was taken to averagely 50 patients into two groups: group (A) patients treated with 131I and group (B) patients treated with 131I plus lithium carbonate. There were no significant difference between the age of two groups (t = 1.019, p > 0.05). Patients in B group were treated with lithium carbonate half one month before and after 131I treatment at a dose of 0.5 g per day (2 × 0.25 g). Each patient received a baseline evaluation, including routine tests of blood, urine and stool, liver and renal functions, thyroid ultrasonography and electrocardiogram. Any patient who had liver or renal disease was excluded from the study.
The study was approved by the investigational review boards and human use committees in Fujian Medical University 2nd Affiliated Hospital.
2.2. Laboratory Study
Thyroid weight was estimated by ultrasonography and careful palpation, and no difference was found between the two groups (t = 0.987, p > 0.05). The dose of 131I was: thyroid weight (g) × (2.59 - 4.44 MBq) per gram of estimated thyroid tissue/24-h radioactive iodide uptake (RAIU) in the thyroid (%), and adjusted according to patients’ age, course of disease, complications, thyroid textures and weight. The average dose of 131I was 240.5 (148 - 444) MBq. And if the therapeutic dose of 131I was more than 370 MBq, two-dose baiting was given at the first dosage of 314.5 MBq and the remains were given after 48 hours. There was no significant difference on the average dose of 131I between two groups (t = 1.049, p > 0.05).
For patients in both groups, radiation absorbed dose rate the front of neck was measured on days 1530 and 45 after the administration of 131I. Serum creatinine and blood urea nitrogen was measured after 15 d of treatment in B group patients, and free T3, free T4 and TSH were tested before and on days 30, 45, 90, 180 after treatment.
2.3. Evaluation
The therapeutic effects of patients were defined during half year visit as follows: 1) Clinical cure. Symptoms and signs of hyperthyroidism totally disappeared after half year visit, with normal rang of serum FT3 and FT4. 2) Improvement. The symptoms alleviated and signs disappeared partially; Serum FT3 and FT4 decreased significantly, but they were still above normal range. 3) Invalid. The symptoms and signs did not ameliorate, even aggravated; Serum FT3 and FT4 did not decrease significantly. 4) Recurrence. The symptoms and signs of hyperthyroidism reappeared, and thyroid hormones rise again after achieving the criteria of clinical cure. 5) Hypothyroidism. The symptoms and signs of hypothyroidism appeared in patients with low thyroid hormones but high TSH.
2.4. Statistical Analysis
Data were analyzed using SPSS 16.0 for Windows. Results were presented as means ± SD for normal distribution and median (M) for skewed distribution. The therapeutic effects of two groups were compared by x-square test. ANOVA with post hoc Dunnett’s T3 test was used to compare serum thyroid hormones and radiation absorbed dose rate the front of neck between two groups before and after treatment. Differences between the two groups of the same period in serum thyroid hormones were evaluated by t test. All p values < 0.05 (two-tailed) were considered to be significant.
3. RESULTS
Our study, after treatment with 31I plus lithium carbonate, showed that serum urea nitrogen and creatinine were in normal range on days 15.
3.1. Dosimetry
Table 1 showed changes in radiation absorbed dose rate the front of neck in A group and B group. The mean 24 h-RAIU before RIT was 87.2% in A and 89.5% in B group, without significant difference (t = 0.887, p > 0.05) between them. After RIT, radiation absorbed dose rate the front of neck decreased gradually as time went on (F = 17.65, <0.01), all of which were significantly higher in B group than that in A group (F = 98.12, <0.01).