Kato Hajime, Hidaka Naoko, Koga Minae, Kinoshita Yuka, Nangaku Masaomi, Makita Noriko, Ito Nobuaki
Division of Nephrology and Endocrinology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Osteoporosis Center, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Int J Endocrinol. 2021 Oct 28;2021:5492267. doi: 10.1155/2021/5492267. eCollection 2021.
Asfotase alfa is the only approved treatment that can normalize mineralization in patients with hypophosphatasia (HPP). Its interference in alkaline phosphatase (ALP) dependent immunoassays has been reported.
To describe thyroid function tests interfered with by asfotase alfa and elucidate the underlying mechanism. . Three patients with HPP treated with asfotase alfa were included. Thyroid hormone levels measured using five different immunoassays with or without ALP as a labeling enzyme during asfotase alfa treatment were evaluated.
After the initiation of asfotase alfa, three HPP patients showed low free triiodothyronine (FT3) and free thyroxine (FT4) measured with AIA-2000 (Tosoh, Tokyo, Japan), an enzyme immunoassay system that uses ALP as a labeling enzyme, but their thyroid-stimulating hormone (TSH) levels were within the normal range. The other CLEIA system using ALP as a label, AIA-CL2400 (Tosoh, Tokyo, Japan), and ALP-independent immunoassay systems demonstrated normal FT3 and FT4 levels. These data suggested that although the thyroid function of these three patients was normal, asfotase alfa interfered with the thyroid hormone measurements made with AIA-2000. AIA-2000 and AIA-CL2400 adopted one-step and delayed one-step measurements, respectively, and the same antibody was used for both immunoassays. However, asfotase alfa may be absorbed on the magnetic beads used in the AIA reagent with the AIA-2000 system but not absorbed on the microparticles used in AIA-CL2400.
Clinicians should be aware of the possible interference in thyroid function measurements by adopting specific types of immunoassays in asfotase alfa-treated HPP patients.
阿法骨化醇是唯一被批准用于使低磷性佝偻病（HPP）患者矿化正常化的治疗方法。已有报道称其会干扰碱性磷酸酶（ALP）依赖性免疫测定。
描述受阿法骨化醇干扰的甲状腺功能测试，并阐明其潜在机制。纳入了3例接受阿法骨化醇治疗的HPP患者。评估了在阿法骨化醇治疗期间使用五种不同免疫测定法（有无ALP作为标记酶）测量的甲状腺激素水平。
开始使用阿法骨化醇后，3例HPP患者使用AIA - 2000（日本东京东曹公司）测量的游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）水平较低，AIA - 2000是一种使用ALP作为标记酶的酶免疫测定系统，但他们的促甲状腺激素（TSH）水平在正常范围内。另一种使用ALP作为标记的化学发光酶免疫分析（CLEIA）系统AIA - CL2400（日本东京东曹公司）以及不依赖ALP的免疫测定系统显示FT3和FT4水平正常。这些数据表明，尽管这3例患者的甲状腺功能正常，但阿法骨化醇干扰了用AIA - 2000进行的甲状腺激素测量。AIA - 2000和AIA - CL2400分别采用一步法和延迟一步法测量，两种免疫测定法使用相同的抗体。然而，阿法骨化醇可能会被AIA - 2000系统的AIA试剂中使用的磁珠吸附，但不会被AIA - CL2400中使用的微粒吸附。
临床医生应意识到在阿法骨化醇治疗的HPP患者中采用特定类型的免疫测定法可能会干扰甲状腺功能测量。
