Barbaro Daniele, Boni Giuseppe, Meucci Giuseppe, Simi Umberto, Lapi Paola, Orsini Paola, Pasquini Cristina, Piazza Francesca, Caciagli Marco, Mariani Giuliano
Sezione Endocrinologia, Diabetologia e Malattie Metaboliche, Spedali Riuniti, Azienda Sanitaria Locale 6, 57100 Livorno, Italy.
J Clin Endocrinol Metab. 2003 Sep;88(9):4110-5. doi: 10.1210/jc.2003-030298.
The main steps in the management of differentiated thyroid cancer are thyroidectomy, treatment with iodine-131 ((131)I), and follow-up with whole-body scanning (WBS) and serum thyroglobulin (Tg) determination. Both (131)I treatment and follow-up require maximum stimulation of normal or pathological thyroid remnants by TSH. The use of recombinant human TSH (rhTSH) has been shown to be useful for follow-up, whereas previous reports are not univocal regarding the use of (131)I postsurgical ablation of thyroid remnants, at least when low doses (30 mCi) of (131)I are administered. A possible explanation for the diminished effectiveness of (131)I treatment after rhTSH may be the interference of iodine content of L-thyroxine (L-T4) therapy during the protocol of administration of rhTSH. We have evaluated the effectiveness of stimulation by rhTSH for radioiodine ablation of postsurgical remnants, stopping L-T4 the day before the first injection of rhTSH and restarting L-T4 the day after (131)I. The study included two groups of patients: group 1 included 16 patients with differentiated thyroid cancer (15 papillary cancers and 1 follicular cancer, stages I and II), who were treated with 30 mCi (131)I with the aid of rhTSH, using the standard protocol but stopping L-T4 as stated previously; and group 2 included 24 patients with the same features (histology and stage) of disease treated with 30 mCi in the hypothyroid state after L-T4 withdrawal. In both groups, serum TSH reached a very good stimulation level [76-210 U/liter (mean, 112 +/- 11 SE) and 38-82 U/liter (mean, 51 +/- 3 SE), respectively]. At the first WBS (after (131)I treatment), all patients showed thyroid remnants. Furthermore, two patients of the first group and three patients of the second group showed lymph node metastases. After 1 yr, all patients were studied again and underwent WBS with a tracer dose of (131)I and serum Tg measurement using rhTSH with the same protocol in both groups. The percentage of ablation (undetectable Tg and a negative WBS) was higher, although not reaching statistical significance, in patients treated with rhTSH: 81.2% in patients treated by rhTSH withdrawal and 75.0% in patients treated by L-T4 withdrawal, respectively. No patient experienced symptoms of hypothyroidism during the 4 d of L-T4 interruption, and serum T4 remained in the normal range. Urinary iodine was analyzed in both groups and compared with a control group of patients who received, for diagnostic purposes, rhTSH without stopping L-T4. In the first group, urinary iodine was 47.2 +/- 4.0 microg/liter (mean +/- SE; P = 0.21 vs. the second group, P = 0.019 vs. control group). In the second group, urinary iodine was 38.6 +/- 4.0 microg/liter (mean +/- SE; P < 0.001 vs. control group); urinary iodine in the control group was 76.4 +/- 9.3 microg/liter (mean +/- SE). Our data show that rhTSH, as administered in the protocol stated previously, allows at least the same rate of ablation of thyroid remnants when low doses (30 mCi) of (131)I are used. The possible role of interference of iodine content in L-T4 is not surprising if we consider that the amount of iodine in 30 mCi is negligible (5 microg) compared with the amount of iodine content in a daily dose of T(4) ( approximately 50 microg). The cost of rhTSH seems modest compared with the high cost of complex therapeutic regimens in other areas of oncology and in consideration of the well-being of patients and of the high level of effectiveness of the treatment.
分化型甲状腺癌管理的主要步骤包括甲状腺切除术、碘 - 131(¹³¹I)治疗以及通过全身扫描(WBS)和血清甲状腺球蛋白(Tg)测定进行随访。¹³¹I治疗和随访均需要促甲状腺激素(TSH)对正常或病理性甲状腺残余组织进行最大程度的刺激。重组人TSH(rhTSH)已被证明对随访有用,而先前关于术后使用¹³¹I消融甲状腺残余组织的报道并不一致,至少在给予低剂量(30 mCi)¹³¹I时如此。rhTSH后¹³¹I治疗效果降低的一个可能解释是,在rhTSH给药方案期间,左旋甲状腺素(L - T4)治疗中的碘含量产生了干扰。我们评估了rhTSH刺激对术后残余组织放射性碘消融的有效性,在首次注射rhTSH前一天停用L - T4,并在¹³¹I后一天重新开始使用L - T4。该研究包括两组患者:第1组包括16例分化型甲状腺癌患者(15例乳头状癌和1例滤泡状癌,I期和II期),他们在rhTSH辅助下接受30 mCi¹³¹I治疗,采用标准方案,但如前所述停用L - T4;第2组包括24例具有相同疾病特征(组织学和分期)的患者,在停用L - T4后处于甲状腺功能减退状态下接受30 mCi治疗。在两组中,血清TSH均达到了非常好的刺激水平[分别为76 - 210 U/升(平均,112±11 SE)和38 - 82 U/升(平均,51±3 SE)]。在首次WBS(¹³¹I治疗后)时,所有患者均显示有甲状腺残余组织。此外,第1组中有2例患者和第2组中有3例患者显示有淋巴结转移。1年后,对所有患者再次进行研究,并在两组中使用相同方案,通过注射示踪剂量的¹³¹I进行WBS和测量血清Tg。在接受rhTSH治疗的患者中,消融百分比(不可检测到Tg且WBS为阴性)更高,尽管未达到统计学意义:rhTSH停药治疗的患者中为81.2%,L - T4停药治疗的患者中为75.0%。在L - T4中断的4天内,没有患者出现甲状腺功能减退症状,血清T4仍保持在正常范围内。对两组患者的尿碘进行了分析,并与一组为诊断目的接受rhTSH但未停用L - T4的对照患者组进行了比较。在第1组中,尿碘为47.2±4.0微克/升(平均±SE;与第2组相比,P = 0.21,与对照组相比,P = 0.019)。在第2组中,尿碘为38.6±4.0微克/升(平均±SE;与对照组相比,P < 0.001);对照组的尿碘为76.4±9.3微克/升(平均±SE)。我们的数据表明,按照先前所述方案给予rhTSH时,在使用低剂量(30 mCi)¹³¹I的情况下,至少能达到相同的甲状腺残余组织消融率。如果我们考虑到30 mCi中的碘含量(5微克)与每日剂量的T4中的碘含量(约50微克)相比可忽略不计,那么L - T4中碘含量的干扰作用就不足为奇了。与肿瘤学其他领域复杂治疗方案的高成本相比,考虑到患者的舒适度和治疗的高有效性水平,rhTSH的成本似乎较为适度。