Elevated serum thyroxine concentration in patients receiving “replacement” doses of levothyroxine
Published Mar 1, 1982 · J. Ingbar, M. Borges, S. Iflah
Journal of Endocrinological Investigation
41
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0
Influential Citations
Abstract
It is commonly believed, as previous reports have indicated, that physiological replacement doses of oral levothyroxine in adults with hypothyroidism generally range between 0.15 and 0.20 mg daily, and that when this dose is administered, serum thyroxine (T4) concentrations are almost always within the normal range. Nonetheless, in two groups of patients receiving suppressive or replacement doses of Synthroid® or Letter®, serum T4 concentrations in more than half were above the normal range for the two different radio immunoassay (RIA) methods employed for analysis. More extensive studies in a group of 28 additional patients receiving Synthroid®, all of whom were euthyroid by clinical criteria, revealed similarly frequent elevations of serum T4 concentration, often of substantial degree. In this group, the level of the serum T4 was not significantly correlated with age, sex, dose per unit weight, or diagnosis. Comparative studies in sera from these patients, and from patients with hyperthyroidism or normal controls, revealed close concordance between values for the serum T4 concentration yielded by two RIA methods and one competitive protein-binding assay. These and other studies provided no evidence that substances other than T4 itself were contributing to the elevations of serum T4 concentration found in patients receiving levothyroxine. Mean values for the resin T3 uptake and free T4 index (FT4I) were increased. Despite elevations in serum T4 concentration and the FT4I, serum 3, 5, 3′-triiodothyronine (T3) concentrations were within the normal range, T3 /T4 concentration ratios in patients receiving Synthroid® being significantly lower than in normal controls. Serum 3, 3′, 5′-T3 (reverse T3, rT3) concentrations displayed a highly significant correlation with serum total T4 concentrations, and the mean value for the group as a whole was significantly elevated. The discordance between the present and previous findings with respect to the serum T4 concentration is ascribed to methodological errors introduced by the methods of measurement employed in earlier reports. It is concluded that, in patients receiving levothyroxine therapy, the serum T3 concentration correlates better with the clinical state than the serum T4 concentration does. Elevations of serum T4 concentration in patients receiving levothyroxine therapy do not necessarily indicate that the dosage is excessive.