Minimally invasive human biomarker system reveals difference between tissue thyroid hormone status and serum hormone levels in amiodarone-induced hyperthyroidism

Routine diagnostcs of thyroid function are based on serum TSH and fTH levels. However, there is a large biological emphasis on the local regulatory system to render thyroid hormone (TH) action tissue-specific. The discrepancy betweem clinical symptoms and TH status predicted by serum biochemistry, in certain disease conditions strongly argue for the development of tissue TH economy estimation tools, in order to improve clinical decision-making. Such cases include amiodarone-induced hyperthyroidism (AIH), which may manifest with extremely high TH levels, while the accompanying clinical symptoms of hyperthyroidism are disproportionally mild. In order to resolve this discrepancy, it would be critical to determine the effect of TH at the level of target tissues of the patient, which has not been possible until now. In this cross-sectional, multicenter study, hair follicle (HF) samples were taken from patients with hypothyroidism or hyperthyroidism at the participating endocrine centers, while euthyroid samples were taken from volunteers with confirmed normal thyroid fujnction and no known evidence of endocrine disorders (healthy controls). Enrolled patients were not stratified for ethnicity, lifestyle, comorbidities and background of hypo and hyperthyroidism. Serum and concomittant HF samples were taken the same day, preferably at the same time. Serum TSH, fT4 and fT3 were measured by immunoassays routinely used by the participating centers. Patients were categorized as hypothyroid, euthyroid or hyperthyroid based on their TSH and fT4 values. Ten single hairs were pulled from patient's vertex skin. HF were cut from each single hair and prepared for gene expression analysis. Five hypothyroid, euthyroid and hyperthyroid samples were used for Next Generation Sequencing in order to identify TH sensitive genes as biomarker candidates.