Decline of T3 and elevation in reverse T3 induced by hyperglucagonemia: changes in thyroid hormone metabolism, not altered release of thyroid hormones

Recently we reported that hyperglucagonemia induced by glucagon infusion causes a decline in serum Triiodothyronine (T3) and a rise in reverse T3 (rT3) in euthyroid healthy volunteers. These changes in T3 and rT3 levels were attributed to altered T4 metabolism in peripheral tissues. However, the contribution of altered release of thyroid hormones by the thyroid gland could not be excluded. Since the release of thyroid hormones is suppressed by exogenous administration of L-thyroxine (L-T4) in appropriate dosage, we studied thyroid hormone levels for up to 6 hours after intravenous administration of glucagon in euthyroid healthy subjects after administration of L-T4 for 12 weeks. A control study was conducted using normal saline infusion. Plasma glucose rose promptly following glucagon administration demonstrating its physiologic effect. Serum T4, Free T4 and T3 resin uptake were not altered during both studies. Glucagon infusion induced a significant decline in serum T3 (P less than 0.01) and a marked rise in rT3 (P less than 0.01) whereas saline administration caused no alterations in T3 or rT3 levels. Thus the changes in T3 and rT3 were significantly different during glucagon study when compared to saline infusion. (P less than 0.01 for both comparisons). Therefore, this study demonstrates that changes in serum T3 and rT3 caused by hyperglucagonemia may be secondary to altered thyroid hormone metabolism in peripheral tissues and not due to altered release by the thyroid gland, since the release of thyroid hormones is suppressed by exogenous L-T4 administration.