Current Thyrotropin Immunoassays Recognize Macro-Thyrotropin Leading to Hyperthyrotropinemia in Females of Reproductive Age.

Abstract

Macro-thyrotropin (macro-TSH) is a high molecular weight form of TSH that leads to hyperthyrotropinemia. This study was undertaken to examine the prevalence and nature of macro-TSH in females of reproductive age. Blood samples were taken from 1794 female patients who visited the Hamada Obstetrics and Gynecology Hospital in Tokyo, Japan, complaining of infertility. The serum of 305 patients with TSH concentrations >2.5 mIU/L was screened for macro-TSH by the polyethylene glycol method. Samples with TSH precipitation ratios by polyethylene glycol >70% were further analyzed using gel filtration chromatography (GFC), protein G columns, and 125I-TSH binding experiments. Screening of the 305 patients revealed that 63 had serum TSH precipitation ratios >70%. GFC revealed that immunoreactive TSH, with a molecular weight of approximately 150 kDa, eluted at higher ratios (79.6 ± 24.4%) in 27 of the 63 patients compared to 0.4 ± 2.0% in the control group. Serum TSH concentrations in 24 of the 27 patients were spuriously elevated due to human anti-mouse antibodies. Macro-TSH was found in the other three patients, and one of them had detectable anti-TSH autoantibodies. Eight of the remaining 36 patients who did not have high-molecular-weight TSH assessed by GFC had immunoglobulin G-associated TSH. Three commercially available TSH immunoassays (Elecsys®, Centaur®, and Architect®) all recognized macro-TSH leading to the elevated serum TSH concentrations. Macro-TSH was present in 0.17% of infertile women. Commercial TSH immunoassays recognized macro-TSH, resulting in the diagnosis of hyperthyrotropinemia.