Czarnywojtek Agata, Zgorzalewicz-Stachowiak Malgorzata, Budny Bartłomiej, Wasko Ryszard, Florek Ewa, Szczepanek Ewelina, Komar-Rychlicka Krzesislawa, Waligorska-Stachura Joanna, Kurdybacha Peter, Miechowicz Izabela, Ruchala Marek
Department of Endocrinology, Poznan University of Medical Sciences, Poznan, Poland.
Neuro Endocrinol Lett. 2013;34(3):241-8.
Radioiodine therapy (RIT) is frequently used as the definitive treatment in patients with Graves' hyperthyroidism when remission is not achieved with anti-thyroid drugs (ATDs). In this observational study, we intended to examine whether the use of high doses of radioiodine (RAI) [22 mCi (814 MBq)] with prophylaxis of oral glucocorticoids (oGCS) does not exacerbate Graves ophthalmopathy (GO) in smokers and non-smokers, especially regards to the urine level cotinine and ocular changes before and after RIT.
The studied group consisted of 26 smokers, aged 28-61 years and 25 non-smoker patients, aged 21-54 years, respectively. The patients were enrolled to RAI after one-year of ineffective ATDs treatment. Criterion for inclusion in the study were patients with mild GO with hyperthyroidism at diagnosis based on the severity (NOSPECTS) and activity (CAS) scale. All the patients were subjected to RIT with oGCS prophylaxis and evaluated prospectively during a one-year follow-up. The ophthalmological examination was performed at various stages of RIT: initial pre-radioiodine administration, at the time of treatment 6, and 12 months after RAI. The present study is unique, because the urine cotinine measurement was employed to detect nicotine exposure, also in regard to smoking intensity.
In smokers, the values of serum TPO-Abs were statistically significant in the second and six month (p<0.05) and in the second and after one year (p<0.005). The TSHR-Abs concentration was significantly higher in smokers (p<0.05), rising from 22.9±1.2 IU/L before therapy to 29.6±5.3 IU/L - 2 months, 32.6±8.6 IU/L - 6 months, and slightly decreased 28.9±10.6 IU/L - 12 months. These observed changes were statistically different between groups at baseline (p<0.05) and after one-year of follow-up (p<0.005). Mean urine cotinine were considerably higher in smokers comparing to non smokers in each point of observation [903.4±770.0 and 5.2±1.7 ng/mL at baseline (p<0.001), 412.8±277.3 and 3.0±0.6 ng/mL after 2 months (p<0.001), 452.0±245 and 6.6±3.6 after 6 months (p<0.001), 379.4±236.8 and 1.0±1.2 after one year (p<0.001)]. The CAS values in the smoking group before RIT increased statistically from 2.8±0.2 points at baseline to 4.3±0.3 after 6 months, and 4.0±0.5 (12 months), while in the non-smoking patients it was 1.4±0.2, 2.8±0.3 and 2.2±0.2, respectively. The level of urine cotinine correlated positively with CAS and TSHR-Ab in the smoking group (r=0.41; p<0.05) at baseline and during follow-up (2 months: r=0.46; p<0.001, 6 months: r=0.47, p<0.005; 12 months: r=0.46; p<0.005). In the NOSPECS classification, the symptoms changed from mild to moderate, mostly in smoking patients.
当抗甲状腺药物(ATD)治疗无法实现缓解时,放射性碘治疗(RIT)常被用作Graves甲亢患者的确定性治疗方法。在这项观察性研究中,我们旨在研究高剂量放射性碘(RAI)[22毫居里(814兆贝可)]联合口服糖皮质激素(oGCS)预防措施的使用是否不会加重吸烟者和非吸烟者的Graves眼病(GO),特别是关于RIT前后的尿可替宁水平和眼部变化。
研究组分别由26名年龄在28 - 61岁的吸烟者和25名年龄在21 - 54岁的非吸烟者组成。在ATD治疗一年无效后,患者接受RAI治疗。根据严重程度(NOSPECTS)和活动度(CAS)量表,纳入研究的标准为诊断时患有轻度GO合并甲亢的患者。所有患者均接受oGCS预防的RIT治疗,并在一年的随访期间进行前瞻性评估。在RIT的不同阶段进行眼科检查:放射性碘给药前初始阶段、治疗后6个月和RAI后12个月。本研究具有独特性,因为采用尿可替宁测量来检测尼古丁暴露情况,也涉及吸烟强度。
在吸烟者中,血清TPO - Abs值在第2个月和第6个月(p < 0.05)以及第2个月和一年后(p < 0.005)具有统计学意义。吸烟者的TSHR - Abs浓度显著更高(p < 0.05),从治疗前的22.9±1.2 IU/L升至29.6±5.3 IU/L(2个月)、32.6±8.6 IU/L(6个月),并在12个月时略有下降至28.9±10.6 IU/L。这些观察到的变化在基线时(p < 0.05)和随访一年后(p < 0.005)在组间具有统计学差异。在每个观察点,吸烟者的平均尿可替宁水平均显著高于非吸烟者[基线时分别为903.4±770.0和5.2±1.7 ng/mL(p < 0.001),2个月后为412.8±277.3和3.0±0.6 ng/mL(p < 0.001),6个月后为452.0±245和6.6±3.6(p < 0.001),一年后为379.4±236.8和1.0±1.2(p < 0.001)]。吸烟组RIT前的CAS值从基线时的2.8±0.2分在6个月后统计学上升至4.3±0.3分,12个月时为4.0±0.5分,而非吸烟患者分别为1.4±0.2分、2.8±0.3分和2.2±0.2分。吸烟组基线时及随访期间(2个月:r = 0.46;p < 0.001,6个月:r = 0.47,p < 0.005;12个月:r = 0.46;p < 0.005)尿可替宁水平与CAS和TSHR - Ab呈正相关。在NOSPECS分类中,症状大多在吸烟患者中从轻度变为中度。
1)对于轻度GO的吸烟者和非吸烟者,采用预防性口服泼尼松的消融性RIT剂量是一种安全的治疗方法;2)事后分析表明,尿可替宁水平在评估RIT前后眼科临床症状的加重情况时非常有帮助,特别是在吸烟者中。