Macro-TSH Interference in Thyroid Function Testing: a Case Report and Literature Review.

Abstract

Background: TSH (Thyroid-Stimulating Hormone) is a key hormone secreted by the pituitary gland, which controls the production and release of thyroid hormones (T4) and triiodothyronine (T3) through a negative feedback mechanism. TSH plays a crucial role in the diagnosis and treatment of various thyroid diseases; however, TSH testing may be affected by a variety of factors, leading to inaccurate test results. The main interferents include heterophilic antibodies, thyroid hormone autoantibodies (THAb), and macro-TSH. These interferents may cause TSH test results to be falsely elevated or reduced.

Methods: In thyroid function testing, chemiluminescence immunoassay (CLIA) is a commonly used technique that uses chemiluminescence-labeled antibodies to detect specific levels of thyroid hormones and TSH. In this case, the patient had no history of thyroid disease. When thyroid test results do not match clinical symptoms, and the changes in TSH, free triiodothyronine (FT3), and free thyroxine (FT4) do not conform to the rules, it is necessary to exclude the presence of test interferents. The patient had no history of rodent contact, so interference from heterophilic antibodies was temporarily not considered. Our laboratory's preferred method for excluding interference from large molecular substances is PEG6000 treatment.

Results: Routine thyroid function tests showed a TSH level of 16.1751 µIU/mL, higher than the normal reference range (0.3500 - 4.9400 µIU/mL). FT3 was 3.47 pmol/L (reference range 2.43 - 6.01 pmol/L), FT4 was 13.10 pmol/L (reference range 9.01 - 19.05 pmol/L), TT3 was 0.96 nmol/L (reference range 0.88 - 2.33 nmol/L), and TT4 was 74.12 nmol/L (reference range 62.68 - 150.84 nmol/L). After treatment with the PEG6000 precipitation method, the TSH test result in the patient's serum dropped to 0.98 µIU/mL, within the normal range.

Conclusions: TSH testing is crucial for the diagnosis and treatment of thyroid diseases. Accurate TSH levels are essential for determining thyroid function status, guiding treatment plans, and monitoring disease progression; this case emphasizes the importance of identifying and excluding the influence of interfering factors in thyroid function testing. Interfering factors, such as the presence of macro-TSH, can lead to clinical misdiagnosis and mis-treatment. The mechanism and clinical significance of macro-TSH formation are not yet fully elucidated, and the combination of anti-TSH antibodies with TSH may be the main cause of macro-TSH formation. All macro-TSH patients show positive anti-TSH antibodies, but not all patients with positive anti-TSH antibodies will form macro-TSH. When thyroid function test results do not match clinical symptoms or the changes in TSH, FT3, and FT4 do not conform to the rules, it is necessary to exclude the presence of test interferents such as macro-TSH. In this case, the normalization of TSH levels after treatment with the PEG6000 precipitation method confirmed the presence of macro-TSH in the patient's serum, thus avoiding unnecessary treatment.