We thank Dr. Weiss for underscoring a potential renal mechanism by which L-thyroxine normalizes the hyperhomocysteinemia seen in hypothyroidism. To examine the relation between homocysteine and GFR, we retrospectively examined serum creatinine levels (as a surrogate for GFR) in 13 of the 14 patients for whom frozen specimens were still available from our study.

We confirm the findings of Kreisman and Hennessey (1) indicating a decline in serum creatinine levels in hypothyroid persons after the attainment of euthyroidism with L-thyroxine replacement. The median serum creatinine values decreased significantly from the hypothyroid to the euthyroid state—from 1.0 mg/dL (range, 0.8 to 1.8 mg/dL) to 0.8 mg/dL (range, 0.6 to 1.1 mg/dL), a difference of 0.2 mg/dL (range, 0.0 to 0.7 mg/dL), or 23.1% (range, 0% to 39%) (sign test, P < 0.001). The positive association between plasma homocysteine and serum creatinine levels in the hypothyroid state (Spearman rank correlation r = 0.69; P = 0.009) adds further credence to a cause-and-effect linkage between elevated homocysteine levels and reduced GFR, whereas the lack of a relation between the decline in homocysteine and creatinine levels after therapy (r = 0.39; P = 0.19) does not. We conclude that the exact mechanisms by which L-thyroxine normalizes the elevated circulating homocysteine levels in hypothyroidism requires further study. Regardless, the major finding of our reported study still stands: namely, that L-thyroxine replacement therapy corrects the hyperhomocysteinemia of hypothyroidism.