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

Abstract

Background:

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.

Methods:

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.

Results:

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.

Conclusions:

Macro-TSH was present in 0.17% of infertile women. Commercial TSH immunoassays recognized macro-TSH, resulting in the diagnosis of hyperthyrotropinemia.