CLN Daily

Thyroid Function Tests in Focus

By Jessica M. Colón-Franco, PhD

Thyroid disease affects millions of individuals worldwide and many do not know they have it. Thyroid function tests (TFTs), such as thyroid stimulating hormone (TSH) and free thyroxine (fT4), are cornerstones for disease diagnosis and monitoring. To this end, the interpretation and analytical performance of TFTs must be robust enough to support those roles. Yet TFTs are confounded by biological and diurnal variation, severe illness, non-pathological states such as pregnancy, and inter-assay variability. In a field so highly dependent on these laboratory tests, how can we minimize these confounding factors?

Professional guidelines for diagnosing and managing thyroid illnesses offer direction on best practices for the use and interpretation of TFTs, but the evidence-based applicability of TFTs is hampered by the wide variability of results across commercial immunoassays. While clinical laboratories have dealt with this using assay-specific reference intervals, this approach does not meet state-of-the-art standards.

Fortunately, efforts toward standardization and harmonization of TFTs are ongoing with the goal of using universal reference intervals. Age- and trimester-specific reference intervals are needed for accurate thyroid function assessment in pediatric and pregnant individuals, respectively, adding another layer of complexity to this issue. All of these issues are coming into focus during the AACC Annual Scientific Meeting.

The burden of thyroid disease in pregnancy and post-partum is significant. For this reason, thyroid disease during this period often is characterized by challenging TFT interpretation. On Monday, Joely Straseski, PhD, and Ann Gronowski, PhD, discussed how normal pregnancy affects the physiology and functions of the thyroid gland in the session, “Update on Thyroid Disease in Pregnancy.” Gronowski described the usual order of thyroid changes during pregnancy: 1) increase in serum TBG, 2) increase in total T4 and total T3, 3) hCG stimulation of the thyroid, 4) increase in serum thyroglobulin, and 5) increase in renal iodine clearance. “These changes underlie the need for trimester-specific reference intervals,” Gronowski noted.

The complexities of thyroid physiology and illness in the pregnancy and post-partum periods have generated controversy about whom and how to screen, with various professional guidelines offering insight. Straseski contrasted recent guidelines. “Laboratories need to be clear about the population and the method used to derive trimester-specific reference intervals for TSH,” Straseski said. She added that recommendations to use total T4 and the free T4 index, an outdated test, in lieu of free T4, remain controversial.

To learn more about the latest in TFTs, attendees can today hear from Ronald Whitley, PhD, Katleen Van Uytfanghe, PhD, and Gregory Brent, BS, MD, who on Wednesday will expand on efforts to develop reference methods for TFTs in the session, “Accurate Measurement of Thyroid Hormones in Disease and Pregnancy.”

Under the Centers for Disease Control and Prevention (CDC), the International Federation of Clinical Chemistry (IFCC) established the Committee for Standardization of TFTs (C-STFT). This group has established a framework for TSH and FT4 reference measurements and the use of universal reference intervals. Van Uytfanghe, a member of the C-STFT, plans to show how, after applying the reference measurement systems, clinical laboratories will be able to use common reference intervals within certain limits. Her talk will be followed by Brent’s on the clinical challenges of thyroid testing and by Whitley’s on the transition to accurate measurement of thyroid hormones.

Significant steps have been taken to improve the quality of TFTs, with the roadmap for implementation in clinical laboratories still under development by C-STFT. Van Uytfanghe will emphasize how C-STFT is focused on getting as many stakeholders as possible on board to support implementation of standardized and harmonized assays.