Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals

Qian Sun; Lívia Avallone; Brian Stolze; Katherine A Araque; Yesim Özarda; Jacqueline Jonklaas; Toral Parikh; Kerry Welsh; Likhona Masika; Steven J Soldin

doi:10.1177/2042018820922688

Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals

Ther Adv Endocrinol Metab. 2020 May 27:11:2042018820922688. doi: 10.1177/2042018820922688. eCollection 2020.

Authors

Affiliations

¹ Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
² Clinical laboratory, Hospital São Camilo, Dasa, São Paulo, Brazil.
³ Endocrinology Pituitary Disorders Center, Pacific Neuroscience Institute, John Wayne Cancer Institute, Santa Monica, CA, USA.
⁴ Department of Medical Biochemistry, Faculty of Medicine, Uludag University, Bursa, Turkey.
⁵ Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University, Washington, DC, USA.
⁶ Program in Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
⁷ Department of Laboratory Medicine and Pathology/National Health Laboratory Service Walter Sisulu University, Mthatha, South Africa.
⁸ Department of Laboratory Medicine, Clinical Center, National Institutes of Health, 10 Center Drive, Building 10, Office:2C429, Bethesda, MD 20892-0001, USA.

Abstract

Background: There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method.

Methods: Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis.

Results: Our study revealed significant uptrend in AM to PM FT4 (p < 0.0001) samples, downtrend in AM to PM TT3 (p = 0.0004) and FT3 samples (p < 0.0001), and AM to PM uptrend in rT3 samples (p < 0.0001). No difference was observed for TT4 between AM and PM. No significant sex differences were seen for any of the five thyroid hormones.

Conclusion: When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement.

Keywords: diurnal variation; mass spectrometry; reference interval; thyroid hormone.