2021). Since T4 hormones are also metabolized by UGTs, the induction of liver enzymes by Phenytoin may contribute to the observed clearance of T4. T4 serum levels were weakly but significantly decreased after 4 weeks of high-dose Phenytoin treatment, see Fig. 1B. The systemic depletion of T4 would also result in an increase of TSH via the hypothalamic–pituitary–thyroid axis feedback loop (McClain 1989) and later on, if the concentrations are high enough and the exposure time is long enough, in thyroid follicular hypertrophy and thyroid tumors (Hill et al. 1989; Curran and DeGroot 1991). The gene discussed is CD4; the disease is thyroiditis.