Endocrine Abstracts

Objective: Serum TSH and thyroid hormone (TH) levels are routinely used as main measures of thyroid function. While these are highly valuable markers, it is becoming more evident that under specific conditions, their predictive power for tissue TH status is limited due to the highly complex nature of tissue-specific TH signaling. This led to a high demand for human tissue TH action markers that could allow the characterization of tissue TH economy. Therefore, our goal was to develop a biomarker system for minimally invasive assessment of TH status using human hair follicles. The biomarker-based prediction model was used to assess the correlation of tissue TH status and blood TH levels in amiodarone treated (≥1-month, AMIO) patients.

Methods: To identify thyroid hormone regulated genes in the human hair follicles (HF), Next Generation Sequencing (NGS) followed by qPCR validation was performed on HF of hypo, eu- and hyperthyroid patients. Only patients without thyroid disease were included in the euthyroid group. Hair follicles were also collected from AMIO patients (treatment longer than 1-month) diagnosed as hypo, eu or hyperthyroid.

Results: Seventeen differentially expressed TH-responsive genes were selected with NGS as potential biomarkers followed by validation with Taqman qPCR on at least 52 independent samples. Four genes showing at least 3-fold change in expression were used to build a classification model with multinomial logistic regression (sensitivity for hypo-, eu-, hyperthyroid classification 0.79; 0.82; 0.81 respectively) to predict TSH-based status of samples (39 hypo-; 55 eu-; 42 hyperthyroid patients; 62.5% female). This model was deployed to determine if measured serum TSH and tissue marker expressions of AMIO patients (41% female, 20 hypo-; 44 eu-; 15 hyperthyroid) correlate similarly to calibrator samples. We found that AMIO patients with TSH in the hypo- or euthyroid range had hypo- or euthyroid marker gene expression patterns, respectively. However, the prediction model indicated that 73% of AMIO patients with hyperthyroid TSH (Me= 0.001 IQR: 0.001-0.013) and fT4 (Me= 56.3 IQR: 29-66.8) levels did not have tissue hyperthyroidism. This discrepancy could be due to the inhibitory action of AMIO on several steps of TH transport, metabolism and signaling.

Conclusions: To assess human tissue TH economy, we developed a minimally invasive qPCR-based biomarker system using hair follicles and built a prediction model. Our model indicates that most AMIO patients diagnosed as hyperthyroid are not hyperthyroid at the tissue level. This corresponds to the lack of unambiguous hyperthyroid symptoms in this patient group.