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

Abnormalities of TH – the definition It refers to the ability of thyroid gland to produce its hormones that are either too high or too low for the body requirements Thyroid gland may be overactive to produce excess or under active to produce less ones www.merrium- webster.com

TH abnormalities --The background Although THs are not strictly necessary for life, yet they have profound effects on: Many physiological processes like body growth, development and metabolism TH are essential for CNS development in children Deficiency of TH is not compatible with normal life www.hormone.org – www.vivo.colostate.edu/hbooks

TH abnormalities –The types TH abnormalities may be related either to excess or deficiency and affects all the body cells These cells are the targets for the thyroid hormones TH abnormalities occur both in children and adults www.hormone.org

TH abnormalities – the excess Excess of TH refers to hyperthyroidism Thyroid gland is overactive and produces too much TH than body requirements It is also called as Thyrotoxicosis Thyroid speeds up body metabolism www.hormone.org/diseases

Hyperthyroidism in general elevated T4/3 ,normal TSH TH excess is characterized by increase in the : Basal metabolic rate(BMR), oxygen consumption and Heat production through hydrolysis of ATP There is elevation of FT3 / FT4 with normal TSH www.hormone.org/diseases

Metabolic effects of Thyrotoxicosis 2 types These are divided into 2: Hyperthyroid effects Metabolic effects on Proteins, Lipids and CHO

Hyperthyroid effects Weight loss and cold tolerance due to↑ in BMR /heat production Warm/ wet hands and high colored skin due to : hyper dynamic circulation Rapid pulse, brisk reflexes and peripheral tremors for: nervous excitation Bulging and perfused eyes for unknown cause www.hormone.org/diseases - www.mayoclinic.org

Perfused skin, eyes and face

Hyperthyroidism – Bulging eyes

Metabolic effects of hyperthyroidism Hyperthyroidism affects the metabolism of : Proteins Lipids and Carbohydrates(CHO)

Effects on Protein metabolism Promotes protein breakdown /Proteolysis of Skeletal muscles and releases more AAs in plasma. Promotes Gluconeogenesis for ↑ in plasma AAs Proteolysis reduces body weight; muscle weakness, body growth and development in children Inhibits protein synthesis/ Proteogenesis

Effects on Lipid metabolism promotes Lipolysis TH excess stimulates Lipolysis and ↑ FFAs level Promotes FA oxidation to generate extra energy Reduces TG synthesis/ Adipose tissue mass and Lowers Plasma Cholesterol and TG

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

The deficiency of TH 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 This condition is more common in females

Hypothyroidism in general ↑TSH normal FT3/T4 Hypothyroidism results in slowing down of Basal metabolic rate – BMR and reduction in : Body metabolism; Oxygen consumption and heat production and hydrolysis of ATP There is elevation of TSH with normal TF4/FT3

Metabolic effects of Hypothyroidism These are divided into 2: Hypothyroid effects Metabolic effects on the Proteins; Lipids and CHOs

Hypothyroid effects These include : Weight gain and non pitting oedema for the S/C deposition of muco polysaccharides/Glycos aminoglyscans /GAGs Skin is thick; rough, hairless and cold for the hypo dynamic circulation Face is expression less due to oedema and S/C deposition of GAGs Pulse/heart rate is slow, reflexes are low and patient is sluggish mentally for the nervous depression

Hypothyroidism – Mental sluggishness

Hypothyroidism in a female – swollen/ expression less face

Non pitting edema of feet

Pretibial Myxoedema

Hypothyroidism – the metabolic effects Hypothyroidism affects the metabolism of : Carbohydrate Lipids and Proteins

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

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

Hypothyroidism - Effects on CHO metabolism cont. Produces hyperglycemia and Diabetes mellitus ↓ glycogen synthesis (Glycogenesis) and its storage in liver ↑ in the S/C deposition of Glycosaminoglycans/GAGs producing non pitting edema – a hallmark of hypothyroidism

Hypothyroidism in infants and children congenital 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/ 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

Comparison B/W Insulin and Glucagon