This research projects wants to improve accuracy and applicability of endocrine diagnostics testing in clinical practice. It continues a long tradition of steroid hormone oriented clinical research at our department, in close collaboration with the Laboratory for Hormonology at the department of Clinical Biology (UZ Ghent).

Steroid hormones such as testosterone or vitamin D are vital for human physiology. In circulation, steroid hormones bind to albumin and specific binding proteins (BP) with only a small fraction circulating freely. The ‘free hormone hypothesis’ suggests that this free fraction best reflects the biological activity. Though experimental and clinical data support this, routinely available methods measure total steroid hormone levels. Relying on total hormone levels could lead to misrepresentation of the hormonal status, especially in conditions where BP production is altered (organ failure, obesity, pregnancy), impairing correct diagnosis and treatment. Direct free hormone measurements are only performed in specialized research labs and not available in clinical routine. Formulas to estimate free steroid hormone concentrations have been developed, but their applicability in many clinical conditions is questionable, so is the correctness of therapeutic actions based on these results.

With BEED-ED, and FWO-TBM sponsored research project in collaboration with UZ Ghent and KU Leuven / UZ Leuven, we will improve the clinical applicability of free steroid hormone concentrations in patients with specific conditions by using state-of-the-art methodology. Specifically, we will establish reference ranges in healthy subjects and investigate the reliability of free hormone estimates in individuals with alterations in BP production and/or binding affinity. Based on these findings, we will improve current formulas and, if needed, develop condition-specific calculators to better estimate free hormone levels. We will evaluate the impact of frequently used BP assays on calculated free steroid hormone results and survey the use of free hormone calculators and access to direct measurements in Flanders and Europe. Ultimately, the project will result in the development of clinical sample workflows based on screening of free steroid hormone levels by calculation and if needed sample referral to reference laboratories for direct measurements.

Further, in the SHAOLIN study, we will study biochemical changes during the insulin tolerance test and the corticotropin (ACTH) stimulation test. These tests are routinely used for the evaluation of the adrenal sufficiency but challenged by lack of standardized reference values. Primary objectives include comparison between different measurement techniques for stress hormone levels during an insulin tolerance test and an ACTH stimulation test (Synacthen® test) and based on these results the proposition of new reference values. Secondary objectives include measurement of free cortisol levels and analyses of more novel stress hormones during these tests.