Interference factors of simultaneous increase of T3, T4 and TSH

Recently, the clinical laboratory scholars of Cleveland Clinic (the second largest medical group in the United States, second only to Mayo Clinic) reported a case where the test results of T3, T4, FT3 and FT4 were inaccurate due to the interference of autoantibodies. The case report was published on Clinical Biochemistry (impact factor: 3.281).

A 74 years old woman who received levothyroxine replacement therapy for hypothyroidism had elevated thyroid stimulating hormone (TSH), free tetraiodothyronine (FT4) and free triiodothyronine (FT3).

Because of the fear of hyperthyroidism, the doctor stopped levothyroxine and started further examination. Pituitary MRI showed microadenomas, but GS α Normal. The pituitary adenoma secreting TSH was suspected, so octreotide treatment was performed. However, her TSH level was still very high (11.73-58.674 mIU/L) and the levels of FT4 and FT3 were not improved. Therefore, it was suspected that the detection values of FT4 and FT3 might be inaccurate.

The levels of FT4 and FT3 were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). It was found that the levels of FT4 and FT3 were not high (ft3:1.54 pg/ml, ft4:1.2 ng / dl). So levothyroxine treatment was restarted and the symptoms improved. The patients pituitary microadenomas were also identified as non secretory.

To determine the cause of interference in routine immunoassay, further tests were performed after normalization of TSH in patients. The researchers conducted relevant tests using two commercial immunoassay methods, and the results showed that there was little difference from the initial assay.

Subsequently, the researchers used polyethylene glycol (PEG) to precipitate the sample and then carried out immunoassay again. The results showed that the T4 and T3 values were reduced by more than 2 times.

The researchers believe that this result indicates that there are autoantibodies against T4 and T3 hormones, and these thyroid hormone autoantibodies (thaas) are also the cause of interference in immunoassay.

The investigators suggest that when thyroid hormone is elevated but TSH is not suppressed, the test error should be considered. LC-MS/MS and other methods that are not easily disturbed by autoantibodies can be used for verification.