Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Department of Endocrinology, Kaiser Permanente, Panorama City, CA 91402, USA.
J Clin Endocrinol Metab. 2024 Nov 18;109(12):3254-3263. doi: 10.1210/clinem/dgae286.
Serum thyroglobulin (Tg) measured by immunometric assay (IMA) is prone to underestimation due to Tg autoantibody (TgAb) interference, often prompting reflex Tg measurement by liquid chromatography/tandem mass spectrometry (MS) or radioimmunoassay (RIA).
IMA, MS, and RIA methodologies were used to measure serum Tg in TgAb-negative (TgAb-) and TgAb-positive (TgAb+) patients with either distant metastatic differentiated thyroid cancer (DTC) or hyperthyroidism (HY)-patients in whom a detectable serum Tg would be expected.
When TgAb was absent, all methodologies detected Tg in the sera of all DTC and HY patients and reported appropriate Tg trends and treatment responses for DTC patients with progressive distant metastatic disease, albeit with high between-method variability (> 30% coefficient of variability). When TgAb was present, all methodologies reported lower serum Tg levels for both DTC and HY groups vs their respective TgAb- group. No Tg was detected by IMA or MS in ∼50% TgAb+ DTC patients (6% had no Tg detected by RIA). Surprisingly, 5% of TgAb+ HY patients also had no Tg detected by IMA or MS. The inverse log TgAb/log Tg correlations seen for the TgAb+ HY patient group with all methods suggested the presence of a TgAb-associated serum Tg-lowering effect.
(i) Between-method Tg variability necessitates method continuity when monitoring the Tg trends of TgAb- DTC patients. (ii) The presence and concentration of TgAb appeared to have a lowering effect on serum Tg measured by all methodologies (IMA, MS, and RIA). (iii) Since the reliability of Tg measured in the presence of TgAb is often uncertain, the TgAb trend (measured by the same method) may be a useful surrogate DTC tumor marker.
由于甲状腺球蛋白自身抗体(TgAb)的干扰,免疫分析法(IMA)检测血清甲状腺球蛋白(Tg)容易出现低估,这通常会促使通过液相色谱/串联质谱(MS)或放射免疫分析(RIA)进行反射性 Tg 测量。
在 TgAb 阴性(TgAb-)和 TgAb 阳性(TgAb+)的甲状腺癌远处转移(DTC)或甲状腺功能亢进(HY)患者中,使用 IMA、MS 和 RIA 方法测量血清 Tg,这些患者的血清 Tg 预计是可检测到的。
当 TgAb 缺失时,所有方法都在所有 DTC 和 HY 患者的血清中检测到 Tg,并报告了 DTC 患者进行性远处转移性疾病的适当 Tg 趋势和治疗反应,尽管存在高方法间变异性(>30%变异系数)。当 TgAb 存在时,所有方法都报告了 DTC 和 HY 组的血清 Tg 水平均低于各自的 TgAb-组。大约 50%的 TgAb+DTC 患者(6%的患者通过 RIA 未检测到 Tg)通过 IMA 或 MS 未检测到 Tg。令人惊讶的是,5%的 TgAb+HY 患者也通过 IMA 或 MS 未检测到 Tg。所有方法均显示 TgAb+HY 患者组的 Tg 与 TgAb 的对数呈负相关,这表明存在 TgAb 相关的血清 Tg 降低效应。
(i)当监测 TgAb-DTC 患者的 Tg 趋势时,需要连续使用方法,以减少方法间 Tg 的变异性。(ii)TgAb 的存在和浓度似乎对所有方法(IMA、MS 和 RIA)测量的血清 Tg 具有降低作用。(iii)由于 TgAb 存在时 Tg 的可靠性通常不确定,因此 TgAb 趋势(通过相同方法测量)可能是一种有用的替代 DTC 肿瘤标志物。