A concurrent loss of function in DIO2, the enzyme that enhances T3 availability (Figure 1) leads to a significant amelioration of the abnormal TH state in the serum [53] and brain [45] of DIO3-deficient mice, suggesting that DIO2 activity is exacerbating the thyrotoxicosis caused by impaired TH clearance by DIO3. Here, TH is linked to thyrotoxicosis.