Increased Fat and Skeletal Muscle j3-Adrenergic Receptors but Unaltered Metabolic and Hemodynamic Sensitivity to Epinephrine In Vivo in Experimental Human Thyrotoxicosis

Based largely on evidence of increased target tissue i-adrener-gic receptor densities and responsiveness in animal and, to a lesser extent, human tissues, it is often assumed that thyroid hormone excess results in increased sensitivity to catechol-amines in vivo, thus explaining several clinical manifestations of thyrotoxicosis. To test the hypothesis that thyrotoxicosis results in increased target tissue fl-adrenergic receptor densi-ties and correspondingly increased metabolic and hemody-namic sensitivity to epinephrine in vivo, we measured these in 10 normal humans before and after administration of triio-dothyronine (100 sg daily) for 10 d. Thyrotoxicosis increased fl-adrenergic receptor densities in fat (- 60%) and skeletal muscle (- 30%). Despite increments infl-adrenergic receptor densities in these and probably other target tissues, metabolic and hemodynamic sensitivity to epinephrine in vivo was unal-tered. An apparently adaptive increase in insulin secretion plausibly explains normal glycemic, glycogenolytic/glycolytic, lipolytic, and ketogenic sensitivity to epinephrine in the thyro-toxic state. In view of this striking homeostatic efficiency of the intact individual, the finding of altered adrenergic recep-tors, even in relevant target tissues, should not be extrapolated to altered sensitivity to catecholamines in vivo in the absence of direct testing of that hypothesis. With respect to the clinical issue, these data suggest that increased sensitivity to catechol-amines does not explain clinical manifestations of thyrotoxico-sis in humans