103
monodeiodination pathways (conversion of T4 to T3) during obesity leads to
increased levels of FT3 among obese subjects. Production of T3 is increased with
decreased production of rT3 (reverse T3) in obesity compared to equal production
of both rT3 and T3 in normal weight individuals [15]. Available data conclude elevated thyroid levels as a consequence rather than a cause of obesity.
Elevated levels of TSH in obese individuals cause the decreased expression of
TSH receptors and ultimate down regulation of TH receptors and actions. As a consequence, the levels of serum TSH and fT3 are further increased in obesity [16].
Hence, it is concluded that TSH secretion is impaired in obesity [17].
Thyroid Hormones and Diabetes Mellitus
Since autoimmune thyroiditis is an important aetiological factor in both hyper- and
hypothyroidism. It is not unusual to find concomitant autoimmune thyroid dysfunction (AITD) and type 1 diabetes (which is also autoimmune in nature) with prevalence of AITD in almost 17–30% of type 1 diabetics [18]. The risk of involvement
of genetic factors in the co-occurrence of both diseases can never be ruled out.
Among the susceptibility factors of concurrence of thyroid disorders and diabetes
type 1, mutations in major histocompatibility complex (MHC) locus on chromosome 6p21, protein tyrosine phosphatase, non-receptor type 22 (PTPN22), which
encodes lymphoid tyrosine phosphatase, a negative regulator of T-cell antigen
receptor (CD3: CD3 (cluster of differentiation 3)) signalling and the cytotoxic
T-lymphocyte antigen-4 (CTlA4) gene have both been confirmed as major joint
susceptibility genes for type 1 diabetes and AITD. The prevalence of impaired thyroid functioning is highest in patients with type 1 diabetes [19].
Thyroid Hormones Regulation of Glucose Homeostasis
Thyroid hormones regulate glucose balance in body in different ways: regulation of
glucose homeostasis, modification of circulating insulin levels and counter regulatory hormones, intestinal absorption of glucose, hepatic production of glucose and
uptake of glucose by peripheral tissues [20]. Thyroid hormone maintains glucose
homeostasis by working with two opposite mechanism; insulin antagonism and
insulin synergism. These hormones act differently at different action sites of insulin
such as adipose tissues, liver and skeletal muscles.
1. Insulin antagonism (liver): TH produces insulin antagonistic effects by increasing the hepatic gluconeogenesis and glycogenolysis as well as by increasing the
intestinal absorption of glucose. The T3 is believed to increase the expression of
glucose-6 phosphatase which facilitates gluconeogenesis and glycogenolysis by
hydrolysis of glucose 6 phosphate. Thyroid hormones also influence other
enzymes involved in hepatic gluconeogenesis such as phosphoenol pyruvate
6 Impaired Thyroid Function in Metabolic Disorders
monodeiodination pathways (conversion of T4 to T3) during obesity leads to
increased levels of FT3 among obese subjects. Production of T3 is increased with
decreased production of rT3 (reverse T3) in obesity compared to equal production
of both rT3 and T3 in normal weight individuals [15]. Available data conclude elevated thyroid levels as a consequence rather than a cause of obesity.
Elevated levels of TSH in obese individuals cause the decreased expression of
TSH receptors and ultimate down regulation of TH receptors and actions. As a consequence, the levels of serum TSH and fT3 are further increased in obesity [16].
Hence, it is concluded that TSH secretion is impaired in obesity [17].
Thyroid Hormones and Diabetes Mellitus
Since autoimmune thyroiditis is an important aetiological factor in both hyper- and
hypothyroidism. It is not unusual to find concomitant autoimmune thyroid dysfunction (AITD) and type 1 diabetes (which is also autoimmune in nature) with prevalence of AITD in almost 17–30% of type 1 diabetics [18]. The risk of involvement
of genetic factors in the co-occurrence of both diseases can never be ruled out.
Among the susceptibility factors of concurrence of thyroid disorders and diabetes
type 1, mutations in major histocompatibility complex (MHC) locus on chromosome 6p21, protein tyrosine phosphatase, non-receptor type 22 (PTPN22), which
encodes lymphoid tyrosine phosphatase, a negative regulator of T-cell antigen
receptor (CD3: CD3 (cluster of differentiation 3)) signalling and the cytotoxic
T-lymphocyte antigen-4 (CTlA4) gene have both been confirmed as major joint
susceptibility genes for type 1 diabetes and AITD. The prevalence of impaired thyroid functioning is highest in patients with type 1 diabetes [19].
Thyroid Hormones Regulation of Glucose Homeostasis
Thyroid hormones regulate glucose balance in body in different ways: regulation of
glucose homeostasis, modification of circulating insulin levels and counter regulatory hormones, intestinal absorption of glucose, hepatic production of glucose and
uptake of glucose by peripheral tissues [20]. Thyroid hormone maintains glucose
homeostasis by working with two opposite mechanism; insulin antagonism and
insulin synergism. These hormones act differently at different action sites of insulin
such as adipose tissues, liver and skeletal muscles.
1. Insulin antagonism (liver): TH produces insulin antagonistic effects by increasing the hepatic gluconeogenesis and glycogenolysis as well as by increasing the
intestinal absorption of glucose. The T3 is believed to increase the expression of
glucose-6 phosphatase which facilitates gluconeogenesis and glycogenolysis by
hydrolysis of glucose 6 phosphate. Thyroid hormones also influence other
enzymes involved in hepatic gluconeogenesis such as phosphoenol pyruvate
6 Impaired Thyroid Function in Metabolic Disorders