Implementing reference systems for thyroid function tests - A collaborative effort.

Measurements of thyroid stimulating hormone (TSH) and free thyroxine (fT4) are critical for the early detection of thyroid diseases and for monitoring treatment. The IFCC Committee for Standardization of Thyroid Function Tests (C-STFT) established reference systems for TSH harmonization and FT4 standardization, and is now working national partners on implementing these reference systems. These implementation activities include the maintenance of the reference systems, their use to standardize and harmonize assays, and educational activities to inform stakeholders about anticipated changes in measurement values as a result of standardization and harmonization. The IFCC C-STFT formed a network of reference laboratories for FT4 and is creating a new harmonization panel for TSH. The U.S. Centers for Disease Control and Prevention is a member of the reference laboratory network and is launching a formal standardization program for FT4. In Japan, national organizations successfully implemented TSH harmonization and established harmonized reference intervals for TSH. The C-STFT made available on its website research findings about potential concerns, communication needs and benefits of FT4 standardization and is assisting local organizations with communicating changes related to these standardization and harmonization efforts. Implementation of fT4 standardization and TSH harmonization is a complex, continuous task that requires collaboration with IVD manufacturers, laboratories, physicians and health care providers. C-STFT is working successfully with national organizations and local groups on improving FT4 and TSH measurements.

National Bone Health Alliance Bone Turnover Marker Project: current practices and the need for US harmonization, standardization, and common reference ranges.

UNLABELLED: This position paper reviews how the National Bone Health Alliance (NBHA) will execute a project to help assure health professionals of the clinical utility of bone turnover markers; the current clinical approaches concerning osteoporosis and the status and use of bone turnover markers in the USA; the rationale for focusing this effort around two specific bone turnover markers; the need to standardize bone marker sample collection procedures, reference ranges, and bone turnover marker assays in clinical laboratories; and the importance of harmonization for future research of bone turnover markers. INTRODUCTION: Osteoporosis is a major global health problem, with the prevalence and incidence of osteoporosis for at-risk populations estimated to be 44 million Americans. The potential of bone markers as an additional tool for health care professionals to improve patient outcomes and impact morbidity and mortality is crucial in providing better health care and addressing rising health care costs. This need to advance the field of bone turnover markers has been recognized by a number of organizations, including the International Osteoporosis Foundation (IOF), National Osteoporosis Foundation, International Federation of Clinical Chemistry, and Laboratory Medicine (IFCC), and the NBHA. METHODS: This position paper elucidates how this project will standardize bone turnover marker sample collection procedures in the USA, establish a USA reference range for one bone formation (serum procollagen type I N propeptide, s-PINP) and one bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) marker, and standardize bone turnover marker assays used in clinical laboratories. This effort will allow clinicians from the USA to have confidence in their use of bone turnover markers to help monitor osteoporosis treatment and assess future fracture risk. This project builds on the recommendations of the IOF/IFCC Bone Marker Standards Working Group by developing USA reference standards for s-PINP and s-CTX, the markers identified as most promising for use as reference markers. RESULTS: The goals of this project will be realized through the NBHA and will include its governmental, academic, for-profit, and non-profit sector stakeholders as well as major academic and commercial laboratories. Upon completion, a parallel effort will be pursued to make bone turnover marker measurements reliable and accepted by all health care professionals for facilitating treatment decisions and ultimately be reimbursed by all health insurance payers. CONCLUSIONS: Successful completion of this project will help assure health professionals from the USA of the clinical utility of bone turnover markers and ties in with the parallel effort of the IOF/IFCC to develop worldwide bone turnover reference ranges.

High-performance liquid chromatography method to analyze free and total urinary pyridinoline and deoxypyridinoline.

The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption measured in blood and urine and are used to investigate bone metabolism and manage bone diseases. Unfortunately, the currently observed interlaboratory variability caused by inconsistent assay calibration limits the optimal use of these markers. A high-performance liquid chromatography (HPLC)-based assay was developed using synthetic PYD and DPD as calibrators to analyze free and total PYD and DPD in urine. The spectroscopic characteristics of the synthetic calibrators were identical to those of calibrators isolated from bone. The mean intraassay variabilities of the HPLC method were 4.1 and 3.8%, respectively, for total DPD and PYD and 9.8 and 9.5%, respectively, for free DPD and PYD. The mean interassay variabilities were 9.1 and 8.2% for total DPD and PYD and 8.6 and 7.0% for free DPD and PYD, respectively. The mean recoveries were 98.1% for total DPD, 100.8% for total PYD, 98.6% for free DPD, and 94.9% for free PYD. The method exhibits a good correlation with a commercial immunoassay and with other HPLC assays currently used in hospital laboratories.