90 % of thyroid hormones are secreted T 4 and 10 % are released as T 3. However, biologically T 3 is much Important than T 4.

0.02 % of the total T 4 in the plasma is free % of the total T 4 in the plasma is bound Therefore, moderate fluctuations in the rate of T 4 release from the thyroid have only tiny effects on the level of free T 4

Parameter Low Level of Thyroid Hormones High Level of Thyroid Hormones (Hypothyroid) (Hyperthyroid) Basal metabolic rate Carbohydrate metabolism Protein metabolism Lipid metabolism Thermogenesis Autonomic nervous system Gluconeogenesis Glycogenolysis Normal serum [glucose] Gluconeogenesis Glycogenolysis Normal serum [glucose] Synthesis Proteolysis Synthesis Proteolysis Muscle wasting Lipogenesis Lipolysis Serum [cholesterol] Lipogenesis Lipolysis Serum [cholesterol] Normal levels of catecholaminesExpression of β adrenoreceptors

T 3 has greater biological activity for three reasons: 1.T 4 is more tightly bound to plasma proteins than is T 3 (0.02 vs. 0.5 % free) 2.The target converts T 4 (once it has entered the cell) to T 3 3.Thyroid hormone receptor in the nucleus has 10-fold greater affinity for T 3 than T 4

TH raise the rate the hepatic glucose production by increasing hepatic gluconeogenic activity. This effect does not result in increase in plasma glucose, because the pancreas respond by augmenting insulin secretion. TH also enhance the availability of the starting materials required for increased gluconeogenic activity (i.e. glycerol and amino acids) Carbohydrate Metabolism

TH stimulate proteolysis predominantly in muscles. TH also increase protein synthesis. However, TH induced in protein degradation usually outweigh (in order to obtain substrate for Increased hepatic gluconeogeness) a net loss of muscle protein occurs (catabolic effect of increased T 3 ) Protein Metabolism

TH stimulate degradation of triglycerides in adipose tissue in order to obtain required glycerol for the increased hepatic gluconeogenesis. TH in physiological concentrations also enhance lipogenesis and are required for the synthesis of faty acid by liver. High levels of T 3 shift the balance in favor of lipolysis. Lipid Metabolism

TH by accelerating the rates of glucose production, protein synthesis and degradation, as well as of lipogenesis and lipolysis, the TH stimulate energy consumption. Taken together, to the extent that TH stimulate both synthesis and degradation, they promote futile cycles that contribute to the increased O 2 consumption seen in hyperthyroidism. Summary of Effects on Metabolism