Increased fat and skeletal muscle beta-adrenergic receptors but unaltered metabolic and hemodynamic sensitivity to epinephrine in vivo in experimental human thyrotoxicosis.

Based largely on evidence of increased target tissue beta-adrenergic 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 catecholamines in vivo, thus explaining several clinical manifestations of thyrotoxicosis. To test the hypothesis that thyrotoxicosis results in increased target tissue beta-adrenergic receptor densities and correspondingly increased metabolic and hemodynamic sensitivity to epinephrine in vivo, we measured these in 10 normal humans before and after administration of triiodothyronine (100 micrograms daily) for 10 d. Thyrotoxicosis increased beta-adrenergic receptor densities in fat (approximately 60%) and skeletal muscle (approximately 30%). Despite increments in beta-adrenergic receptor densities in these and probably other target tissues, metabolic and hemodynamic sensitivity to epinephrine in vivo was unaltered. An apparently adaptive increase in insulin secretion plausibly explains normal glycemic, glycogenolytic/glycolytic, lipolytic, and ketogenic sensitivity to epinephrine in the thyrotoxic state. In view of this striking homeostatic efficiency of the intact individual, the finding of altered adrenergic receptors, 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 catecholamines does not explain clinical manifestations of thyrotoxicosis in humans.

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