Macro TSH in patients with subclinical hypothyroidism

Objective TSH is a sensitive indicator of thyroid function. In subclinical hypothyroidism, however, serum TSH concentrations are elevated despite normal thyroid hormone levels, and macro TSH is one of the causes. This study aimed to clarify the prevalence and nature of macro TSH in patients with subclinical hypothyroidism. Design We conducted a 2-year cross-sectional observational study. Patients We included 681 patients with subclinical hypothyroidism and 38 patients with overt hypothyroidism (controls). Measurements Macro TSH was screened by polyethylene glycol (PEG) method and analysed by gel filtration chromatography and bioassays. Results Among 681 serum samples, 117 exhibited PEG-precipitable TSH ratios greater than 75% (mean + 1.5 SD in controls) and were subjected to gel filtration chromatography. TSH was eluted at a position greater than 100 kDa in 11 patients with subclinical hypothyroidism (1.62%); these patients were diagnosed with macro TSH. The nature of macro TSH included eight anti-TSH autoantibodies of IgG class, two non-IgG-associated and one human anti-mouse antibody (HAMA). Macro TSH showed low bioactivity. Conclusions Macro TSH was heterogeneous, but it is mostly comprised of TSH and anti-TSH autoantibodies. When PEG-precipitable TSH exceeds 90% in serum samples with TSH above 10 mU/l, clinicians should strongly suspect the presence of macro TSH and confirm it by gel chromatography. Because macro TSH exhibited low bioactivity, thyroid hormone replacement therapy may not be required in patients with subclinical hypothyroidism due to macro TSH except for those with high serum free TSH levels.