Estimation of a physiologic replacement dose of levothyroxine in elderly patients with hypothyroidism.

We gave graded doses of levothyroxine sodium to 11 elderly hypothyroid subjects (mean age, 66.1 years). The daily levothyroxine sodium dose was initially 75 micrograms or less, and was increased by 25 micrograms every six weeks. Serum total thyroxine, total triiodothyronine, and basal thyrotropin levels were measured at the start of the study and at the end of each six-week dose period. A protirelin (thyrotropin-releasing hormone) test was performed when the thyrotropin level returned to normal. Mean daily levothyroxine sodium doses that normalized serum thyrotropin levels and protirelin test were 110 +/- 8 micrograms and 113 +/- 9 micrograms, respectively. Serial basal thyrotropin determinations during stepwise increments in levothyroxine dose indicated physiologic hormone replacement. As determined in our elderly patients, levothyroxine replacement dose was a third less than that formerly recommended.

Identification and properties of myocardial myoglobin as a binder of iodothyronines.

Gel filtration of dog myocardial cytosol previously incubated with [125I]T4 or [125I]T3 revealed hormone binding in three fractions, one of which, M-2, was presumptively identified as myoglobin by absorbance maximum, molecular weight and specific immunodiffusion. Gel chromatography of purified horse or dog myoglobins incubated with labeled T3 or T4 resulted in coelution of the myoglobin and iodothyronine peaks. Excess unlabeled thyroid hormone displaced no more than 25% of tracer bound to myoglobin. Acid-acetone fractionation of myoglobin into heme and globin, and subsequent precipitation of the heme, localized hormone binding to the heme moiety. Hematin (ferric state heme) in solution was also shown to bind thyroid hormone. Added to human sera which were then subjected to T3 or T4 radioimmunoassay, myoglobin reduced detectable, endogenous iodothyronine by 77 and 26%, respectively. The myoglobin effect was concentration dependent. Heart myoglobin, like hemoglobin in the erythrocyte, is a cytoplasmic heme protein responsible for a major fraction of binding of intracellular iodothyronine. The nature of the interaction between iodothyronines and the heme prosthetic group is unclear.