Pathophysiology of Hyperthyrodism and Hypothyroidism

The general effect of thyroid hormone is to activate nuclear transcription of large numbers of genes. Therefore in virtually all cells of the body, great number of protein enzymes, structural proteins, transport proteins, and other substances are synthesized.

The thyroid hormone increases the metabolic activities of almost all the tissues of the body. The basal metabolic rate can increase to 60 to 100 per cent above normal when large quantities of hormones are secreted. The rate of utilization of foods for energy is greatly accelerated. The rate of protein synthesis as well as the rate of protein catabolism is also increased. The growth rate of young people is greatly accelerated. The mental processes are excited, and the activities of most of the other endocrine glands are increased.

Hyperthyroidism	Normal Thyroid Function	Hypothyroidism
Heat intolerance Warm skin, sweaty palm	Increases the number and activity of mitochondriaà Increases ATP Increases active transport of ions through cell membraneàIncreases response of Na+/K+ ATPaseàIncreases usage of energy and heat production (newly formed erythrocytes have higher 2,3-DPG) àIncreased Oxygen consumptionàIncreased Basal Metabolic Rate	Cold intolerance Cold, dry skin Shivering Decreases Ca2 uptakeà Skeletal muscle defect
	Bodily Specific Mechanism
Long standing: Increased insulin antagonism Impaired glucose tolerance Reversible Diabetes Mellitus	Stimulation of Carbohydrate metabolism: -rapid uptake of glucose by the cells -enhanced glycolysis, glycogenolysis -enhanced gluconeogenesis -increased rate of absorption  from the GI tract -increased insulin secretion	Decreased glucose uptake by cellàdecreased energy production for the muscleàlethargy Long standing: Impaired glycogenolysis, gluconeogenesis, Hypoglycemia
Lipolysis,  hyperlipidacidemia	Stimulation of Fat metabolism: -Lipids are mobilized rapidly from the fat tissues -Increased free fatty acids in plasma -Greatly accelerates the oxidation of FFA by the cells -Increase rate of cholesterol secretion in the bile and consequent loss in the feces by induces increases numbers of LDL receptor on the liver. Overall:  Increase plasma FFA, decrease plasma cholesterol, phospholipids and triglycerides.	Reduced lipolysisàweight gain, hyperlipidemia(VDL, LDL) -Hypercholesterolemia: PE; Xanthelamasta, Xanthoma Investigation: Increased serum cholesterol -Risk factor for atherosclerosis, HPT, Stroke and MI
Increases proteolytic enzyme in hyperthyroidism Excess proteolysis, increase in urea formation and excretion Muscle mass reduced, muscle weakness	Protein Metabolism Promote protein synthesis	Decreased protein for normal hair growth à easy loss of hair brittle nail
Increased Adult: Osteroporosis, hypercalcemia, hypercalciuria Children: accelerated growth	Bone metabolism	retarded growth in children
Relative Vitamin Deficiency	Increases Requirements for Vitamins for synthesis of enzyme and coenzyme
Increased hunger without weight gain Decreased body weight due to lipolysis, protein catabolism (Skinny people who eat a lot)	Decreased Body Weight Increased Appetite	Loss of appetite without weight loss Weight gain due to water retention (Fat people who don’t eat)
	Cardiovascular System
60 percent or more above normal cardiac output GFR increased, RPF increased, Na+ reabsorption increased	Increased blood flow and cardiac output -Rapid utilization of oxygen than normalàRelease of greater than normal quantities of metabolic end products from the bodyàVasodilation àIncreased blood flow	50 percent of normal cardiac output
Tachycardia AF occasionally occur Urgent: treat with beta blocker	Increase beta-receptorà sensitize target organ to catecholaminesàincreased heart rate	Bradycardia Marked thyroid hormone deficiency: heart failure, pleural and pericardial effusion
Heart strength depressed because of long standing protein catabolism Severe thyrotoxicosis pt could die of cardiac decompensation secondary to myocardial failure and to increased cardiac load imposed by increased cardiac output.	Increased enzymatic activityàincreased heart strength
Hyperventilation	Increased Respiration Increased oxygen utilization increase the rate and depth of respiration	Hypercapnia, hypoxia
Diarrhea	Increased GI motility Increased secretion of the digestive juices and the motility of the GI tract	Constipation Impaired absorption in the gut of iron, folic acid and Vit B12à anemia Impaired in gastric and oesophageal musculatureàGastric reflux, oesophagitis
Hyperreflexia, tremor(assessed by placing a sheet of paper on extending fingers), muscle weakness Psychoneurotic tendencies: anxiety complexes, extreme worry, paranoia	Excitatory effects on neuromuscular ability	Abnormal loss of sensation, hyporeflexia, slow movement, loss of memory, clouding of consciousness, coma
Constant tiredness but difficult to sleep	Effect on sleep	Extreme somnolence, lasting 12 to 14 hours a day.
	Effect on other endocrine gland: -Increased of tissue need for certain hormone: 1.       Glucose metabolism; insulin 2.       Bone formation; Parathyroid hormone 3.       Increase rate of inactivation of glucocorticoid; feedback increased of ACTH
Increased estrogen: Female: Amenorrhea, oligomenorrhea, infertility Pregnant woman: Spontaneous abortion Male: Loss of libido, impotence Signs of increased estrogen: Palmar erythema, spider nevi, gynaecomastia	Sexual Function: Thyroid metabolized steroid into estrogen	Decreased estrogen: Menorrhagia Or corresponding increase of prolactinàinhibition of gonadotropin releaseà Amenorrhea, loss of libido, impotence

Hyperthyroidism

Increased accumulation of mucopolysaccaride also cause thickening of eardrum--> deafness and also large tongue--> slurred speech

Neonatal screening of thyroid function should be performed on all newborns. Treatment starts immediately after diagnosis established. L-thyroxine tablet be crushed, mixed with breast milk or water and be fed to the infant, should not be mixed with any iron-containing products.

In children, hypothyroidism also causes retarded longitudinal growth and delayed epiphyseal function.

Cretinism = severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormone

Enlargement of thyroid gland(goiter) due to tumour or stimulation by TSH or TSI. Thyroid hormone either decreased(in marked iodine deficiency or enzyme defect) or increased (eg. in Graves'disease)

Reference: Medscape, Color Atlas of Pathophysiology, Nadi, Guyton and Hall Medical Physiology, Malaysia Pediatric Protocol, Some websites and Wiki

Notes to come: Congenital Hypothyroidism (endemic, genetic, sporadic), immunology of endocrine disease, thyroid function test, drugs for thyroid diseases.