Glucagon-induced changes in plasma thyroid hormone concentrations in healthy dogs resemble "euthyroid sick syndrome"

We recently demonstrated that glucagon infusion induced a decline in T3 and a rise in rT3 in anesthetized dogs. These changes in T3 and rT3 may be attributed, at least in part, to anesthesia itself, since general anesthesia is known to cause lowering of T3 and an elevation in rT3 during the perioperative period. Therefore, to eliminate the contribution, if any, of anesthesia to these changes in T3 and rT3, we assessed plasma glucose, T3 resin uptake (T3RU), T4, free T4, T3 and rT3 concentrations following intravenous glucagon (0.5 mg) or normal saline (0.5 ml) administration at frequent intervals for 3 h in 6 conscious dogs fasted for 16 h. No significant alterations were noted in T4, free T4, and T3RU levels during either study. However, glucagon infusion alone induced a significant fall in T3 (0.33 +/- 0.06 in nmol/l vs -0.03 +/- 0.03 nmol/l with normal saline; p less than 0.01) and marked elevations in glucose (3.66 +/- 0.22 mmol/l vs 0.61 +/- 0.11 nmol/l with normal saline, p less than 0.001) and rT3 concentrations (0.11 +/- 0.02 nmol/l vs 0.005 nmol/l; p less than 0.001). Furthermore, the integrated responses of T3 and rT3 as assessed by cumulative changes and areas under the curves were markedly greater during glucagon infusion when compared with saline administration (p less than 0.01 for all comparisons). Since the elevations in levels of stress hormones known to ensue during anesthesia do not occur during a conscious resting state, we believe that hyperglucagonemia may be a major contributor of thyroid hormone alterations observed in several euthyroid sick states, not associated with stress, and may enhance these changes during euthyroid sick syndrome associated with stressful crises. Finally, these changes may be attributed to altered metabolism of iodothyronines in peripheral tissues as reflected by lowered T3/T4 and increased rT3/T4 ratios.