Thyroid hormones 3 – the Abnormalities Lecture NO: 2nd MBBS Dr Muhammad Ramzan

TH abnormalities - the definition It refers to the ability of the thyroid gland to produce its secretions that are too high or too low for: The body requirements THs can be produced in excess or there may be deficiency of THs Both the conditions give rise to important clinical conditions that are not compatible with comfortable life

TH abnormalities --The background Although TH are not strictly necessary for life. They have profound effects on many physiological processes like development , growth and metabolism Deficiency of TH is not compatible with normal life

TH abnormalities –The types TH abnormalities may be related either to: Deficiency or excess and affects all the body cells – the Targets for the thyroid hormones

TH abnormalities – the excess Thyroid is over active Excess of TH refers to hyperthyroidism Thyroid gland is overactive in hyperthyroidism and produces more hormones than body requirements It is also called as Thyrotoxicosis

TH excess – Hyperthyroidism in general ↑ FT4 FT3 and normal TSH TH excess is characterized by : Increase in Basal metabolic rate - BMR Increased heat production and oxygen consumption through increased hydrolysis of ATP Elevation of FT3 / FT4 with normal TSH

Effects of Hyperthyroidism Effects of hyperthyroidism are classified into 2 based upon the effects on various tissues/nutrients Hyperthyroid effects Effects on the metabolism of : Proteins, Lipids and Carbohydrates

Hyperthyroid effects Hyperthyroid effects include: Weight loss due to ↑in body metabolism/BMR Warm hands with high coloured skin; rapid and irregular pulse, perfused eyes for hyper dynamic circulation Tolerance to cold for ↑BMR Tremours of hands for nervous excitibility Exophthalmose – reason ?

Hyperthyroidism – perfused face

Hyperthyroidism – Bulging eyes/ Exophthalmos

Excess of TH – the metabolic effects Hyperthyroidism affects the metabolism of : Carbohydrates (CHO) Lipids and Proteins

Effects on Protein metabolism TH excess increases protein breakdown /Proteolysis and releases more amino acids in plasma. Promotes Gluconeogenesis for ↑ in plasma Amino acids Proteolysis results in reduction of body weight; muscle weakness, growth and development in children Reduces protein synthesis/ Proteogenesis

Effects on Lipid metabolism promotes lipolysis TH excess stimulates fat mobilization leading to lipolysis and increases : Free fatty acid level in plasma Fatty acid oxidation to generate energy Reduces TG synthesis and adipose tissue mass and Lowers Plasma Cholesterol and TG

Effects on Carbohydrate (CHO) metabolism TH stimulate all the aspects of CHO metabolism and promotes the : intestinal absorption of glucose Glucose uptake by the body cells and glycolysis Break down of glycogen – Glycogenolysis Reduces glycogen synthesis/ Glycogenesis and Increases Gluconeogenesis

TH abnormalities – The deficiency Thyroid gland is underactive It is the inability of thyroid gland to produce enough TH for body requirements. Thyroid gland is under active The condition is called hypothyroidism or myxoedema It is more common in females

TH deficiency /hypothyroidism in general ↑TSH normal FT3/T4 Hypothyroidism results in slowing down of basal metabolic rate – BMR and Reduction in : Metabolism; Oxygen consumption Heat production and hydrolysis of ATP Elevation of TSH, normal TF3 or FT4

Effects of hypothyroidism Effects of hypothyroidism are classified into 2 based upon the effects on various tissues/nutrients Hypothyroid effects Effects on the metabolism of : Proteins, Lipids and Carbohydrates

Hypothyroid effects These effects include: Weight gain for the subcutaneous deposition of Muco polysaccharides Dry; rough and hairless skin for ===== Expression less face, non pitting /pretibial oedema ==A diagnostic sign Cold hands and extremities for slow circulation Low body temperature and cold indolence for ↓BMR Slow reflexes and mental sluggishness for Mental depression Constipation

Hypothyroidism – Mental sluggishness

Hypothyroidism in females – swollen/ expression less face

Non pitting edema of feet

Pretibial Myxoedema

Deficiency of TH – the metabolic effects TH deficiency suppresses the metabolism of : Carbohydrate Lipids and Proteins

The deficiency – Effects on protein metabolism Hypothyroidism reduces Proteogenesis and promotes proteolysis especially in skeletal muscles Excess of glucoplastic amino acids are released from the skeletal muscle break down These Amino acids are used as substrate for hepatic Gluconeogenesis

The deficiency – Effects on Lipid metabolism Dyslipidemia is commonly observed in hypothyroidism This includes ↑ in plasma levels of : TG, Total Cholesterol and LDL- Cholesterol Low HDL- Cholesterol Increase in body adipose tissues and reduction in fatty acid oxidation

TH deficiency – Effects on CHO metabolism Hypothyroidism suppresses : All aspects of CHO metabolism Reduces intestinal absorption of glucose and uptake of glucose by the body cells (Skeletal muscles and Fatty tissues) Lowers Glycolysis, release of energy and ATP production and body temperature

The deficiency – Effects on CHO metabolism cont. Produces hyperglycemia/ Diabetes mellitus for inhibiting Insulin secretion and promoting its degradation ↓ glycogen synthesis (Glycogenesis) and its storage in liver ↑Deposition of Glycosaminoglycans,mucopolysaccarides and Hyaluronic acid under the skin giving rise to : Non pitting edema – a hallmark of hypothyroidism

TH deficiency in infants and children Juvenile hypothyroidism Congenital hypothyroidism refers to hypothyroidism A deficiency or lack of TH at birth If deficiency of TH is not detected earlier, it will lead to deficiency in IQ and development of CNS

Hypothyroidism in infants and children – the presentation Infants are lethargic ,have slow movements and low body temperature They have big head, protruding tongue , puffy face and feeding problems Results of treatment are excellent ,if started earlier