Larsen Camilla Bøgelund, Petersen Eva Rabing Brix, Overgaard Martin, Bonnema Steen Joop
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Eur Thyroid J. 2021 Mar;10(1):93-97. doi: 10.1159/000509184. Epub 2020 Aug 21.
Analytical problems should be considered in case of a discrepancy between the results of biochemical tests and the clinical findings. Macro-hormones often artefactually elevate biochemical tests.
A young male was referred with persistently elevated TSH (148 mIU/L) measured by a sandwich electrochemiluminescence immunoassay, ECLIA (Cobas; Roche, Basel, Switzerland). The patient's complaints were unspecific, and he appeared clinically euthyroid. The plasma levels of free T4 and free T3 were within the normal range, thyroid autoantibodies were negative, and thyroid ultrasonography was normal. During a short trial of thyroid hormone substitution, the level of TSH decreased to near-normal levels, but hyperthyroid symptoms emerged. TSH analysed by a different immunoassay (Architect; Abbott, Chicago, IL, USA) yielded similar results. In addition, serial dilutions were performed showing linearity, without detection of heterophilic antibody interference. Gel filtration chromatography confirmed the presence of macro-TSH.
The patient harboured macro-TSH, which is a rare condition. The complex binding of TSH to other plasma proteins, most often immunoglobulins, results in elevated plasma TSH. However, the biologically active fraction of TSH is normal, reflected by clinical and biochemical euthyroidism.
当生化检测结果与临床发现存在差异时，应考虑分析方面的问题。大分子激素常常会人为地使生化检测结果升高。
一名年轻男性因采用夹心电化学发光免疫分析法（ECLIA，Cobas；罗氏公司，瑞士巴塞尔）测得促甲状腺激素（TSH）持续升高（148 mIU/L）而前来就诊。患者的症状不具特异性，临床检查显示甲状腺功能正常。游离T4和游离T3的血浆水平在正常范围内，甲状腺自身抗体呈阴性，甲状腺超声检查也正常。在短期甲状腺激素替代治疗试验期间，TSH水平降至接近正常水平，但出现了甲状腺功能亢进症状。采用另一种免疫分析法（Architect；雅培公司，美国伊利诺伊州芝加哥）分析TSH，结果相似。此外，进行了系列稀释，显示呈线性，未检测到嗜异性抗体干扰。凝胶过滤色谱法证实存在大分子TSH。
该患者存在大分子TSH，这是一种罕见情况。TSH与其他血浆蛋白（最常见的是免疫球蛋白）的复杂结合导致血浆TSH升高。然而，TSH的生物活性部分是正常的，这在临床和生化甲状腺功能正常中得以体现。
