PEG Precipitation to Detect Macro‐TSH in Clinical Practice: A Systematic Review

Macro-thyroid-stimulating hormone (macro-TSH) is a complex formed by monomeric TSH with anti-TSH antibodies, causing falsely elevated TSH levels and potential misdiagnosis of hypothyroidism. Identification of macro-TSH is essential for proper treatment and patient follow-up. Its diagnostic gold standard is gel filtration chromatography (GFC), which is very expensive, time-consuming, and rarely available. Polyethylene glycol (PEG) precipitation is more accessible and inexpensive. The aim of the study was to review evidence on PEG precipitation for the detection of macro-TSH to standardize its application in clinical practice. Methods: According to PRISMA guidelines, we conducted up to August 2024 a comprehensive search of PubMed and Scopus databases, using terms related to macro-TSH and PEG precipitation. Results: We included 23 studies with 4476 subjects, encompassing 10 observational studies and 13 case series/reports. All studies showed a low risk of bias. They were conducted in tertiary centres and included newborns to elderly subjects. The most of evidence about the procedure has been achieved with PEG concentrations of 12.5%. The PEG-precipitable TSH of the macro-TSH cases was always higher than 75% ranging on average from 81% to 90%. No-macro-TSH cases (controls) showed a PEG-precipitable TSH percentage ranging from 44.1% to 61.8%. Conclusions: PEG precipitation can be taken into account as a useful diagnostic tool for macro-TSH. However, it is necessary to perform PEG precipitation in cases with a highly suspicious clinical picture and at the same time perform all available ancillary tests. PEG-precipitable TSH > 75% can be considered a reliable diagnostic threshold for macro-TSH cases.