Variability in the detection of macro TSH in different immunoassay systems

DESIGN: Macro TSH is a large molecular-sized TSH that is mostly a complex of TSH and IgG. Patients with macro TSH have elevated serum TSH and normal free thyroxine levels, mimicking subclinical hypothyroidism. The aim of this study was to clarify the degree of cross-reactivity of macro TSH to different commercial immunoassay systems. METHODS: Screening for macro TSH was done using a polyethylene glycol (PEG) method and confirmed with gel filtration chromatography in serum samples from 1901 patients with subclinical hypothyroidism. Interference due to human anti-mouse antibodies (HAMA) was examined using HAMA blockers. TSH was measured with an enzyme immunoassay for the analysis of macro TSH. Serum TSH values in patients with macro TSH were also determined with the widely used commercial immunoassay platforms Elecsys, Centaur and Architect, and the detectability of macro TSH was compared among them. RESULTS: Gel filtration chromatography was performed with 174 serum samples with PEG-precipitable TSH ratios >75%. Twenty serum samples were found to contain large molecular-sized TSH, five of which were due to interference by HAMA. The prevalence of macro TSH was eventually 0.79% (15/1901). Commercial immunoassay systems variably recognized macro TSH. The Architect TSH immunoassay platform was the least reactive to macro TSH, but still recognized it in 60% of macro TSH-containing serum samples. CONCLUSIONS: There were no commercial TSH immunoassay platforms that did not cross-react with macro TSH. Screening for macro TSH should be performed before hormone replacement therapy is initiated for subclinical hypothyroidism.