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Treatment of Hypothyroidism with Once Weekly Thyroxine¹

Endocrine Research Unit, Division of Endocrinology, Mayo Foundation and Clinic (S.K.G.G.), Rochester, Minnesota 55905; and the Departments of Chemical Pathology (R.R.C.), Endocrinology (J.N.F., D.P.C., C.M.F.) and Cardiology (N.A.L.), Wellington Hospital, and the Departments of Pathology (H.C.F.) and Public Health (G.L.P.), Wellington School of Medicine, Wellington, New Zealand

Address all correspondence and requests for reprints to: Dr. Stefan Grebe, Dept. of Pathology, Wellington School of Medicine, Wellington, New Zealand. E-mail: grebs{at}wnmeds.ac.nz

We compared daily T₄ therapy with 7 times the normal daily dose administered once weekly in 12 hypothyroid subjects in a randomized cross-over trial. At the end of each treatment we measured serum free T₄ (FT₄), free T₃ (FT₃), rT₃, and TSH levels and multiple markers of thyroid hormone effects at the tissue level repeatedly for 24 h.

Compared with daily administration, the mean serum TSH before the administration of weekly T₄ was higher (weekly, 6.61; daily, 3.92 µIU/mL; P < 0.0001), and the mean FT₄ (weekly, 0.98; daily, 1.35 ng/dL; P < 0.01) and FT₃ (weekly, 208; daily, 242 pg/dL; P < 0.01) were lower. A minimally elevated serum total cholesterol during weekly administration (weekly, 246.8; daily, 232.6 mg/dL; P < 0.03) was the only evidence of hypothyroidism at the tissue level.

Compared with daily administration, the mean peak FT₄ following weekly administration of T₄ was significantly higher (weekly, 2.71; daily, 1.59 ng/dL; P < 0.0001), as was the mean peak FT₃ level (weekly, 285; daily, 246 pg/dL; P < 0.01). None of the tissue markers of thyroid hormone effect changed compared to daily T₄, and there was no evidence of treatment toxicity, including cardiac toxicity.

During weekly T₄ administration, autoregulatory mechanisms maintain near-euthyroidism. For complete biochemical euthyroidism a slightly larger dose than 7 times the normal daily dose may be required.

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