title: Catabolic effects of thyroid hormone excess: the contribution of adrenergic activity to hypermetabolism and protein breakdown.
abstract: Although patients with thyrotoxicosis improve clinically after treatment with beta-adrenergic blocking drugs, it has never been established whether the hypermetabolism and body protein wasting caused by thyroid hormone excess are actually mediated by adrenergic mechanisms. To evaluate this issue, we measured basal energy expenditure, epinephrine-stimulated calorigenesis, and leucine kinetics (an index of body protein catabolism) in six normal volunteers before and after triiodothyronine (T3) administration (150 micrograms/d for 1 week). Serum T3 rose nearly threefold (P less than 0.001) during T3 administration, producing significant increases in basal metabolic rate (21%, P less than 0.001), nitrogen excretion (45%, P less than 0.001), and leucine flux (45%, P less than 0.01). In response to epinephrine infusion, the absolute rise in metabolic rate above basal was 57% greater in the thyrotoxic condition (P less than 0.02). Although beta-adrenergic blockade with intravenous propranolol totally abolished the calorigenic response to epinephrine, it had no detectable effect on either the accelerated basal metabolic rate or the augmented body protein catabolism caused by thyroid horomone excess. Our data suggest that in the basal, resting state, the increased metabolic rate and accelerated protein breakdown caused by thyroid hormone are not adrenergically mediated. However, under nonbasal conditions (when sympathetic activity is stimulated), enhanced responsiveness to catecholamine calorigenesis may exaggerate the hypermetabolic state and thereby contribute to weight loss and other clinical manifestations of thyrotoxicosis. This mechanism may explain the clinical efficacy of beta-adrenergic blocking agents in the treatment of thyrotoxicosis.
mesh_terms: D000320:Adrenergic Fibers / Q000503:physiopathology*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D001835:Body Weight; D002149:Energy Intake; D004734:Energy Metabolism; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D011433:Propranolol / Q000627:therapeutic use; D011506:Proteins / Q000378:metabolism*; D013971:Thyrotoxicosis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D011506:Proteins; D014284:Triiodothyronine; D011433:Propranolol; D007930:Leucine; D009584:Nitrogen; D004837:Epinephrine