TREATMENT OF HYPOTHYROIDISM WITH ONCE WEEKLY THYROXINE

We compared daily T-4 therapy with 7 times the normal daily dose admin istered once weekly in 12 hypothyroid subjects in a randomized cross-o ver trial. At the end of each treatment we measured serum free T-4 (FT 4), free T-3 (FT3), rT(3), and TSH levels and multiple markers of thyr oid hormone effects at the tissue level repeatedly for 24 h. Compared with daily administration, the mean serum TSH before the administratio n of weekly T-4 was higher (weekly, 6.61; daily, 3.92 mu IU/mL; P < 0. 0001), and the mean FT4 (weekly, 0.98; daily, 1.35 ng/dL; P < 0.01) an d FT3 (weekly, 208; daily, 242 pg/dL; P < 0.01) were lower. A minimall y elevated serum total cholesterol during weekly administration (weekl y, 246.8; daily, 232.6 mg/dL; P < 0.03) was the only evidence of hypot hyroidism at the tissue level. Compared with daily administration, the mean peak FT4 following weekly administration of T-4 was significantl y higher (weekly, 2.71; daily, 1.59 ng/dL; P < 0.0001), as was the mea n peak FT3 level (weekly, 285; daily, 246 pg/dL; P < 0.01). None of th e tissue markers of thyroid hormone effect changed compared to daily T -4, and there was no evidence of treatment toxicity, including cardiac toxicity. During weekly T-4 administration, autoregulatory mechanisms maintain near-euthyroidism. For complete biochemical euthyroidism a s lightly larger dose than 7 times the normal daily dose may be required .