ECE2017 Symposia Tissue specific defects in thyroid hormone action (3 abstracts)
The Netherlands.
Mutations in the thyroid hormone (TH) transporter MCT8 result in the AllanHerndonDudley syndrome (AHDS), which is characterized by severe intellectual and motor disability and high serum T3 levels inducing thyrotoxicity in peripheral organs. At present, no effective treatment is available. Preclinical studies suggest that the T3 analogue Triac is a promising candidate to i) normalize serum T3 levels and thus alleviate the thyrotoxicosis and ii) restore TH signaling in the brain.
Methods: We conduct a world-wide prospective interventional trial in which about 45 AHDS patients receive 1 year Triac treatment. The primary end-point is the reduction of serum T3 levels, and secondary end-points include normalization of heart rate (HR), improvement of body weight (BW) and serum parameters that reflect TH action in peripheral tissues. Neuro(psycho)logical functioning is assessed before and after 1 year of Triac treatment.
Results: Currently, 41 patients (age: 166 years) have been enrolled (median (IQR) follow-up time: 8 (312) months) of whom 18 have completed 1 year of follow-up. Triac treatment effectively suppressed serum TSH levels (2.3 (1.63.9) to 0.9 (0.21.9) mU/l; P<0.001), resulting in a strong reduction of T3 levels (5.0 (3.96.5) to 1.7 (1.42.2) nmol/l; P<0.001). Importantly, BMI, serum HDL cholesterol, creatinine and CK levels significantly increased, whereas basal heart rate and serum SHBG levels significantly decreased.
Discussion: Triac treatment effectively normalizes serum T3 levels. This interim analysis suggests that Triac treatment has beneficial effects on the peripheral phenotype of AHDS, which will be further substantiated upon completion of the follow-up period by the other participants.