Peripheral responses to thyroxine in hypothyroid subjects as a function of dose and duration of substitution

The aim of this study was to explore the differences in normalization between different organ functions in hypothyroid patients during substitution. The study included 21 hypothyroid patients who were substituted with gradually increasing doses of thyroxine (T4) and studied repeatedly for up to 20 or 32 weeks. The different peripheral organ functions were compared with regard to the dose and duration of substitution necessary for a 50% therapeutic effect. The circulatory response to an orthostatic test, the decrease in low density lipoprotein cholesterol and thyroid stimulating hormone concentrations, the lipolytic effect of physical exercise and the increase in triiodothyronine concentration showed a 50% response to substitution within 3.3--4.6 weeks of therapy and at a T4 dose of 0.04--0.06 mg/day. In contrast, the 50% therapeutic effect on the lipolytic response to an intravenous l-noradrenaline infusion and the maximal working capacity on ergometer bicycle was not observed until 6.2--9.0 weeks of therapy and T4 doses of 0.08--0.11 mg/day. The differences observed in the peripheral responses might be of clinical importance when severely hypothyroid patients must be substituted rapidly.