Thyroid gland

Question 1

2 types of thyroid hormone

Answer 1

Thyroxine - T4

Triiodothyronine - T3

• Regulate metabolic rate
• Normal growth and development
• Cretinism associated with abnormal growth of thyroid gland

Question 2

Function of calcitonin

Answer 2

Control of plasma Ca2+

Question 3

Structure of thyroid gland

Answer 3

weighs 20g

Goiter => enlarged gland

• Bilobed with thin isthmus
• Highly vascular - 4-6 ml/min/g

Question 4

Microscopic structure of thyroid gland

Answer 4

Closely packed acini or follicles

WALL

• Single layer of cells
• Columnar - active
• Cuboidal/low columnar - inactive

INTERIOR

• Clear proteinaceous colloid
• Basement membrane
• Mucopolysaccharides

Activity of individual lobules can vary

(photo below - INACTIVE - colloid is large for storage)

Question 5

I Owe Our Cousin Reimbursement

5 steps in synthesis of thyroid hormones

Answer 5

1. Iodide trapping
2. Oxidation
3. Organification
4. Coupling
5. Release

Question 6

Iodide trapping

Answer 6

• Na+ dependent active process
• DIET - Iodide (I-): eggs, seafood, salt - 1mg/week
• Plasma I- = 1-1.5 ug/L

TRAPPING

• Secondary active transport mechanism - Na=/K= ATPase
• Tissue:Plasma [I-]: 20-30:1 // MAX TSH stimulation 200:1

Question 7

Oxidation

Answer 7

• Iodide to iodine I- + I- => I₂
• Catalysed by peroxidase enzymes at cell-colloid interface
• Iodine incorporated into colloid

Question 8

Thyroglobulin of organification

Answer 8

• Glycoprotein (10% CHO)
• MW 660,000
• 2 identical subunits
• 132 tyrosine residues - 25-30 iodinated
• 6-8 go to form iodo-thyronine
• 3-4 molecules T4 per molecule thyroglobulin
• 1 in 5 thyroglobulin molecules have T3

Question 9

Organification

Answer 9

• I₂ coupled to tyrosine residues of thyroglobulin

Question 10

Coupling

Answer 10

• Iodinated tyrosine residues
• Coupling of 2 DITs = T₄
• Coupling of DIT with MIT = T₃

Question 11

Release

Answer 11

• Pinocytosis
• Exocytosis of colloid via pseudopodia - most recently synthesised first used
• Fuse with lysosomes
• Acid proteases break down thyroglobulin
• Iodide conserved by deiodination of MIT & DIT
• 80 ug of T4 & 4ug T3 (10x more potent) released per day
• Release stimulated // TSH

Question 12

Total T₄ in blood

Answer 12

1 x 10^-7 mol/L

Question 13

Total T₃ in blood

Answer 13

2 x 10^-9 mol/L

Question 14

Free circulating T₄

Answer 14

0.03% - 3 x 10^-11 M

Question 15

Free circulating T₃

Answer 15

10^-12 M

Question 16

1. 3 thyroid hormone binding proteins
2. where are they degraded
3. When are they cleared

Answer 16

1. Thyroxin-binding globulin (TBG), Thyroxin binding pre-albumin (TBPA), Albumin
2. Liver
3. 6-7 days for T₄ and 1 day for T₃

Question 17

Hypothalamic Pituitary Thyroid Axis

Answer 17

TRH = Thyrotropin Releasing Hormone

Question 18

Thyrotropin Releasing Hormone

1. Released by
2. What does it use as a 2nd messenger
3. What does it do
4. Where is it degraded

Answer 18

1. Tripeptide released by hypothalamus
2. Acts using Ca2+ as a 2nd messenger
3. Increases secretion of TSH and stimulates prolactin release
4. Rapidly degraded in plasma

-ve feedback via T₃ & T₄

Question 19

TSH

1. Produced by
2. Type of protein
3. normal plasma conc
4. structure
5. actions of TSH

Answer 19

1. Anterior pituitary
2. Glycoprotein - 15% CHO & MW 28000
3. 1 x 10^-12 M
4. 2 peptide chains: alpha = that of LH, FSH, hCG (pregnancy test); specificity lies in beta chain
5. • Increased iodide uptake

• increased synthesis and secretion of T₃ & T₄
• increased vascularity & hypertrophy of thyroid gland

Question 20

Increased basal metabolic rate by thyroid hormone

Answer 20

EUTHYROID

30-40 kCal/m²/hour

HYPERTHYROID

60-65 kCal/m²/hour

HYPOTHYROID

20-25 kCal/m²/hour

Question 21

Increased O2 consumption/heat production by tissues (as a result of thyroid hormone)

Answer 21

EXCEPT

• Brain
• Spleen
• Testes
• Ovary

Thermogenic effect moderated by:

1. Increased blood flow to skin
2. Increased sweating
3. Increased ventilation

CAUSE

• Increased Na+/K+ dependent ATPase
• Futile metabolic cycles

Question 22

What are the 3 metabolic effects of thyroid hormones

Answer 22

1. Increase muscle protein and fat breakdown
2. Increase all aspects of CHO metabolism
3. Increase GI motility

Question 23

Other metabolic effects of thyroid hormones

Answer 23

• Increased HR and contractility
• Increased myosin Ca2+ ATPase gene transcription
• Increased numbers of beta-adrenergic receptors
• Heart
• Skeletal muscle
• Adipose tissue
• Increased sensitivity to catecholamines
• Necessary for normal menstrual cycles

Question 24

Growth and development - pre-natal effects of thyroid hormones

Answer 24

• Not essential for growth
• Required for reproductive, skeletal and CNS system
• Must be of foetal origin

Question 25

Growth & development - post-natal actions of thyroid hormones

Answer 25

* Required for normal growth and development * Acts synergistically with GH on bone growth

Question 26

What happens in primary hypothyroidism

Answer 26

* LACK OF IODIDE * Decreased T3 * Decreased negative feedback * Increased TSH and Increased TRH * Increased growth of thyroid * GOITRE

Question 27

Manifestation of primary hypothyroidism in infancy

Answer 27

* Cretinism * non-reversible * dwarfed stature * poor bone development * muscle weakness * mental deficiency * slow pulse * GI disturbances

Question 28

Manifestation of primary hypothyroidism - juvenile or adult

Answer 28

Chronic thyroiditis - Hashimotos Autoimmune destruction of thyroid gland

Question 29

Sub-acute thyroiditis

Answer 29

* Thyroid inflammation * Initial hyperthyroidism followed by hypothyroidism * transient, reversible * can lead to permanent hypothyroidism

Question 30

Secondary hypothyroidism

Answer 30

Pituitary disease * TSH not biologically active * Selective TSH deficiency - rare genetic disease * Autoimmune destruction of TSH secreting cells

Question 31

Tertiary hypothyroidism

Answer 31

Hypothalamic disease * Tumour * Radiation (common causes)

Question 32

Resistance to thyroid hormones - hypothyroidism

Answer 32

* Resistance at tissue level - rare * Genetic defect in thyroid nuclear receptor

Question 33

What are the clinical findings of hypothyroidism

Answer 33

* Dry rough epidermal layer of skin * Non-pitting puffiness - Mucopolysaccharides, Hyaluronic acid, chondroitin sulphate - Hydrophilic and accumulate water - Myxedema * Course dry hair and hair loss * Decreased sebaceous gland activity - contributes to dry skin * decreased CO =\> bradycardia * Slow reflexes, decreased mental function - memory, alertness * Partial deafness - mucopolysaccharides accumulate in middle ear * Decreased appetite * Weight gain * Cold intolerance * fatigue

Question 34

Hyperthyroidism - thyrotoxicosis

Answer 34

* Excessive ingestion of thyroid hormones * Graves disease is most common (\>60% of cases) - Autimmune LATS, TSH receptor, no feedback - exophthalmus * Toxic multinodular goiter - follicles "autonomy" growth, caused by a benign adenoma * Hyperthyroid phase of thyroiditis - toxic adenoma * Ectopic production site - pituitary tumour producing TSH * Exophthalmus

Question 35

Clinical findings of thyrotoxicosis

Answer 35

* Diffuse goitre * Exophthalamus - oedema ocular muscles - graves * Increased basal metabolic rate * Increased appetite * Weight loss * Heat intolerance * Sweating * Increased HR * Increased contractility - palpatations * Increased systolic BP, decreased diastolic BP * Tremor * Increased nervous alertness and excitability * Irregular menses * Infertility * Increased GI movements * Increased bowel movements * Proximal muscle weakness * Hypokalemic periodic paralysis

Question 36

Treatment of hyperthyroidism

Answer 36

BETA BLOCKERS THIONAMIDES - inhibit thyroid hormone synthesis RADIOACTIVE IODINE - ablation (I¹³¹/I¹²⁵) PERCHLORATE - inhibits iodine trapping NATURAL GOITROGENS - Progoitrin - Cabbages, kale, kohlrabi LITHIUM - Inhibits thyroid hormone release