Measuring deiodinase activity - a need for standardization?

Joëlle Wiersema, Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, location AMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Petra Mohácsik, Laboratory of Molecular Cell Metabolism, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
Balázs Gereben, Laboratory of Molecular Cell Metabolism, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
Arturo Hernandez, Maine Health Institute for Research, Scarborough, ME.
Selmar Leeuwenburgh, Thyroid Center, Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
Marcel Meima, Thyroid Center, Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
W Edward Visser, Thyroid Center, Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.

Abstract

Thyroid hormones are produced in the thyroid gland and metabolized in the peripheral tissues. The major pathway of thyroid hormone metabolism is the removal of an iodine atom from the phenolic or tyrosyl ring by deiodinating enzymes, so-called deiodinases. Three distinct types of deiodinase have been identified, namely type 1 (D1), type 2 (D2) and type 3 (D3), which differ in main function and expression profile. Measuring the activities of D1, D2 and D3 is an indispensable tool in research on thyroid hormone metabolism. At present, only a limited number of research laboratories worldwide measure deiodinase activity using a variety of assays and protocols. Unlike diagnostic labs, research labs rarely participate in external quality control due to limited availability for most analytes or enzymes. However, implementing a quality assurance program for deiodinase assays is crucial to ensure consistent enzyme activity across laboratories. The present study provides the results of a method comparison between five established laboratories with experience in measuring deiodinase activity. The results showed that there are considerable differences in deiodinase activity levels determined by participating laboratories, which could be partially explained by differences in techniques and protocols. We therefore concluded that in most cases, absolute deiodinase activities can only be compared within the same laboratory. External quality control only adds value when all the laboratories use the same technique with their own optimized protocols. The use of internal controls is recommended to ensure that the correct enzymatic activity is being measured over time in the same laboratory.