Quantification of serum thyroid hormones using tandem mass spectrometry in patients with Down syndrome

Abstract

Thyroid dysfunction is common in patients with Down syndrome (DS), the most common chromosomal disorder. Thyroid hormones (THs) are important for normal growth, neurodevelopment, and metabolism, highlighting the importance of quantifying the levels in patients with DS. However, current methods possess cross‐reactivity that results in inaccuracies in quantification. We aimed at developing a new analytical method for quantifying the total 3,3′,5‐triiodo‐l‐thyronine (TT3), total 3,3′,5,5′‐tetraiodo‐l‐thyronine (TT4), 3,3′,5′‐triiodo‐l‐thyronine, and reverse T3 (rT3) levels using LC–MS/MS. Repeatability and reproducibility with coefficient of variation values of 2–9 and 3–13%, respectively, were acceptable, suggesting that the assay was suitable for measuring serum THs. We measured the serum TH levels of patients with DS but without thyroid dysfunction (age, 3–20 years) and compared the levels to those of controls (patients with idiopathic short stature; age, 3–17 years). When TH levels were summarized by age group, the serum TT4 concentrations were not significantly different between the controls and patients with DS across all age groups. Meanwhile, the serum TT3 concentrations differed according to age. In addition, the serum rT3 concentrations were significantly higher in patients with DS than in controls, except for those in the 12–14 age group. We also calculated the T3/T4 and rT3/T4 ratios to elucidate the reason for the higher rT3 in patients with DS; however, no useful findings were obtained. Thus, further investigation is needed to clarify our findings.

Concurrent <i>THRB</i> and <i>DUOX2</i> variants in a patient detected via newborn screening for congenital hypothyroidism: a case of resistance to thyroid hormone

“…At 1 mo of age, a thyrotropin-releasing hormone stimulation test was performed, revealing high baseline and stimulated TSH levels (23.8 μΙU/mL and 113.9 μΙU/mL, respectively). To exclude the possibility of immunologically falsely high values of thyroid hormones, we measured thyroid hormones using the LC-MS/MS method ( 13 ). As expected, the levels of total T3 (2.22 ng/mL; reference: 0.8–2.0), total T4 (164 ng/mL; reference: 47–115), and reverse T3 (0.77 ng/mL; reference: 0.06–0.26) were all higher than the reference intervals.…”