Falsely Elevated Thyroid-Stimulating Hormone (TSH) Level Due to Macro-TSH

We encountered a 60-year-old woman with remarkably elevated thyroid-stimulating hormone (TSH) level as measured by electrochemiluminescent immunoassay (ECLIA), but with no specific symptoms, and with normal levels of free T3 and free T4. We performed the following investigations: polyethylene glycol (PEG) precipitation test, human antimouse IgG antibody (HAMA) interference test, and 3 additional TSH measurements by chemiluminescent immunoassay (CLIA). We then performed 2 gel filtration chromatography (GFC) procedures; one was at pH 7.2, and the other was at pH 3.0. Although the recovery of TSH shown by the PEG precipitation test was 4% which was extremely low, no HAMA interference was observed. Moreover, 3 CLIA instruments also showed various high values. The first GFC showed that the main peak of TSH immunoreactivity by ECLIA was located at a slightly larger molecular weight position than that of IgG. By the second GFC, the sample from the peak fraction of the first GFC showed that the TSH peak disappeared completely at the previous retention time but newly appeared at the same retention time as the TSH monomer. Protein G-Agarose gel removed the majority of the TSH complex. In conclusion, the majority of TSH in her serum was macro-TSH; TSH and anti- TSH IgG autoantibody complex. We should keep the possibility of macro-TSH in mind in cases with unexpectedly high TSH values, especially in autoimmune thyroidal disorders.