1. Dr. Mohammed Kalimi
Thyroid Physiology

6. Iodide Turnover Input = Output
500 μg Iodide = Renal excretion =480 μgI-
(Daily dietary) Stool excretion= μg I -

7. Biosynthesis of TH 1. Iodide pump or trap:
Transport of iodide into the gland against electro chemical gradients by Na+ -I- cotransport (symport)
↑ Na-K ATPase and TSH
Inhibition by Sodium thiocyanate and Perchlorate

8. T/S Ratio Normal T/S 20:1 TSH stimulation 100:1
Hypophysectomized (no TSH) 1:1

9. Biosynthesis of TH 2. Conversion of Iodide to Iodine 2I -  I2
H2O2 sustrate and thyroid peroxidase enzyme
↑ TSH and inhibited by PTU and methimazole

10. Biosynthesis of TH
3. Organification: Formation of MIT and DIT by iodination of tyrosyl residue of TG
4. Coupling: MIT + DIT = T3
DIT + DIT = T4
Organification and coupling are caralyzed by thyroid peroxidase and require hydrogen peroxide and TSH

11. TH Synthesis and Release

12. Administration of large quantities of Iodide (2 mg or more)
 TH synthesis due to
 expression of Na-I symporter
 enzyme peroxidase genes

13. T3 and T4
Plasma bound T4 = 99.97% Plasma free T4 = 0.03% Plasma bound T3 = 99.7% Plasma free T3 = 0.3%

14. T3 and T4 Ten times (of the total) T3 in the blood is free
Compared to T4
Plasma half life of T3 = 1 day
Plasma half life of T4 = 7 days
T3 is two to three times more biologically potent than T4

15. TH blood binding proteins
Thyroxine binding globulins (TBG): binds to about 70% total T4 and 50% total T3
Thyroxine binding prealbumin (TBPA): binds 20% of total T4 ( no binding to T3)
Albumin : binds 10% of total T4 and 50% of total T3

16. Degradation of T4
1. Conversion of T4 to T3 (T4  5’ Deiodinase T3) about 35%
2. Conversion of T4 to rT3 (T4  5 Deiodinase  rT3) about 45%
3. T4 metabolised by cojugation or oxidative deamination : about 20%

17. Reverse T3 Physiological role unknown
Levels ↑ with chronic illness, calorie deprivation, β blockers and corticosteroids

18. Thyroid Physiology Acts on most tissues
Action –slow in onset and long in duration
TH is not necessary for life, improves quality of life

19. TH Actions 1. Growth and Development 2. Metabolic 3. Neural
4. Cardiovascular

20. TH Actions
Normal growth (↑GH)and development (bone, skeletal and brain)
Congenital deficiency ; cretinism
Dwarf stature (bone remains infantile ), mental retardation

21. TH Actions
Metabolic: ↑ BMR, ↑ O2 consumption, ↑ heat production, ↑ mitochondrial ATP synthesis.
Acute response to cold by ↑ BMR, ↑ heat production, ↑ catecholamines, ↑ lipolysis, ↑ cardiac adjustments, ↑ muscular activity
Chronic cold: ↑ conversion of T4 to T3

22. TH Actions ↑ Carbohydrate, protein and lipid metabolism
↑ Gluconeogenesis, ↑ Glycolysis, ↑ absorption of carbohydrates from the GI tract
Negative nitrogen balance (↑ protein turnover)
↑ Lipolysis, FFA synthesis and oxidation
 Total cholesterol and LDL

23. TH Actions Neural: Promotes normal neuronal development
Cardiovascular effects: ↑ heart rate and strength of the heart beat, ↑ ventilation and cardiac output
↑ Cardiac β receptors

24. TH Mechanism of Action

26. TRH Tripeptide Synthesized and released from hypothalamus
↑ T3,T4,  anterior pitutary TRH receptors,  TSH

27. TSH α subunit identical with LH, FSH, hCG β subunit is specific to TSH
Plasma T1/2= 1 hour
Plasma TSH levels = μU/ml
↑ TSH, ↑ cold, ↑ TRH, ↑ leptin
 TSH, sleep, fasting and ↑ somatostatin

28. Goiter ( enlargement of TH gland)
Prolonged and excessive TSH stimulation of TH gland
Euthyroid Goiter: Iodide deficiency, ↑ TSH to compensate  TH
Hyperthyroid Goiter: over secretion of TSI (thyroid stimulating immunoglobulin) which mimics TSH, ↑ TSI, ↑TH
Hypothyroid Goiter: Administration of drugs such as PTU, perchlorate, thiocyanate, TH,↑ TSH

29. TH : Clinical tests Measurement of plasma total T3 and Total T4
Measurement of TSH
Normal values= micro units/ mL of blood
Elevation in serum TSH is the most sensitive measure for primary hypothyroidism

30. TH: Clinical tests
TSH above 5.0 (hypothyroidism) treatment with thyroxine
TSH below 0.5 (hyperthyroidism), radiation treatment plus thyroxine (T4)

32. TH Clinical In deficiency state: Hypothyroidism
Overactivity: Hyperthyroidism

33. Hypothyroidism
Primary disease: Thyroid failure (surgical, immune or iodide destruction of thyroid gland)
Secondary disease: Pituitary (TSH deficiency) or hypothalamus (TRH deficiency)failure
Defective TH receptors
Myxedema
Cretinism

34. Symptoms of hypothyroidism
Decreased BMR , decreased pulse rate and vitality
Increased plasma cholesterol and LDL
Growth failure, weight gain, constipation
Dry scaly thickened skin, cold intolerance
Sluggishness, hoarse voice, lethargic, puffy eyelids, enlragement of tongue
Depression and insomnia

35. Hyperthyroidism
Graves’ disease (Thyrotoxicosis)
↑ TSI, ↑ T3,T4,  TSH

36. Symptoms of hyperthyroidism
↑ BMR
 Plasma Cholesterol and LDL
↑ Cardiac output, ↑ heart rate and ↑cardiac beta receptors, congestive heart failure
↑ Body heat, sweating and vasodialation
Osteoporosis (negative calcium balance)
Hyperkinetic and psychotic behavior
↑ GI malfunctions and weight loss
Neuro muscular-fatigue,hyperactive reflexes
Eye discomfort, marked protrusion of eyes (exophthalamos)

37. Pregnancy and TH
Pregnancy, ↑ Estrogen, ↑TBG,
↑Total plasma T3 and T4