Decline of T3 and Elevation in Reverse T3 Induced by Hyperglucagonemia: Changes in Thyroid Hormone Metabolism, Not Altered Release of Thyroid Hormone

Abstract

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.

3‐Iodothyronamine: a modulator of the hypothalamus‐pancreas‐thyroid axes in mice

“…This effect was prevented by exenatide, supporting a role for glucagon. Consistent with this hypothesis, inhibition of liver deiodinase activities by glucagon has been reported (Mitchell and Raza, 1986;Kabadi and Premachandra, 1988). No change in fT3 was observed after 20 mg·kg -1 T1AM, which might be explained by increased insulin secretion, since insulin is known to stimulate liver deiodinase activities (Sato et al, 1984).…”

Responses of Heat Stressed Chickens to Exogenous Reverse Triiodothyronine (rT3)

“…Lowering the utilization of FFA, rT3 might supplement the lipolyuc effect of glycocorticoids and glucagon. Glycocorticoides as well as glucagon increases plasma rT3 (CHOPRA et al, 1975;LAURBERG and BOYE, 1984;KABADI and PREMACHANDRA, 1988). Catecholamines produced no increase of FFA, thus, chickens behave differently from mammals (LANGSLOW et al, 1970).…”

Thyroid Hormone Indices During Illness in Six Hypothyroid Subjects Rendered Euthyroid with Levothyroxine Therapy

“…However, altered hypothalamic pituitary thyroid axis with inhibition of TSH secretion described during these disease states may also account for altered release of thyroid hormones by the thyroid gland with consequential lowering of both T4 and T3 (Kabadi, 2001;Duntas et al, 1999;Kabadi and Fragstedt, 1995;Adriaanse et al, 1993;Faber et al, 1987;Hamblin et al, 1986;Kabadi 1984;Spencer et al, 1983;Bacci et al, 1982;. Moreover, this impaired TSH secretion may also be responsible for altered metabolism of thyroid hormone in the peripheral tissues as documented in previous studies in animals as well as humans (Duntas et al, 1999;Kabadi and Premachandra, 1988;Kabadi and Fragstedt, 1995;Hamblin et al, 1986;Spencer et al, 1983;Wu, 1983). Alternatively, interference of binding of thyroid hormones to thyroid binding globulin may contribute to lowering of concentrations of both T4 and T3 with a rise in T3 resin uptake (Afandi et al, 2000;Chopra et al, 1986;Oppenheimer et al, 1982;Chopra et al, 1979).…”

“…Alternatively, interference of binding of thyroid hormones to thyroid binding globulin may contribute to lowering of concentrations of both T4 and T3 with a rise in T3 resin uptake (Afandi et al, 2000;Chopra et al, 1986;Oppenheimer et al, 1982;Chopra et al, 1979). Finally, the inhibition of the deiodinase as well as impaired hypothalamic pituitary axis with lowering of circulating TSH concentration have been attributed to rising stress hormones i.e., catecholamines, glucocorticoid, and glucagon (Duntas et al, 1999;Langer et al, 1989;Hidal and Kaplan, 1988;Kabadi and Premachandra, 1988;Langer and Foldes, 1988;Bianco et al, 1987;Faber et al, 1987;Kabadi and Premachandra, 1987;Silva and Larsen, 1986;Chopra et al, 1985;Langer et al, 1985;Kabadi et al, 1982). These hormones also appear to play a role in the interference in binding between thyroid hormones and their binding globulin attributed to elevation of circulating free fatty acids by promoting lipolysis (Afandi et al, 2000;Faber et al, 1987;Chopra et al, 1986;Chopra et al, 1985;Oppenheimer et al, 1982;Chopra et al, 1979).…”