PBL 3: Thyroid Gland

Question 1

where is the thyroid gland located

Answer 1

located in anterior neck, between C5-T1

Question 2

Thyroid gland is an _______ gland. It has two lobes, connected with a middle part called the _______

Answer 2

endocrine

isthmus

Question 3

The thyroid gland sits behind the strap muscles. what are they called

Answer 3

sternohyoid

sternothyroid

Question 4

where are the parathyroid glands found and how many do we have

Answer 4

found on the posterior aspect of the two lobes of the thyroid gland
4

Question 5

the compartment is bound by the __________ fascia

Answer 5

pretracheal

Question 6

what does the Parathyroid gland produce

Answer 6

PTH

Question 7

what are the cell types in the parathyroid gland

Answer 7

chief cells
oxyphil cells
water clear

Question 8

what are the hormones of thyroid gland stored in

Answer 8

stored in cavities, surrounded by secretory cells (follicular cells)

Question 9

what is a thyroid follicle

Answer 9

Small spherical grouping of follicular cells
The outer spherical layer - follicular cells
The inner cavity- colloid core (glycoprotein)

see pics

Question 10

What does the colloid core consist of?

Answer 10

Thyroglobulin- Thyroid hormone precursor proteins

Question 11

where are the parafollicular/C cells found

Answer 11

in between the follicular cells

Question 12

what do parafollicular/C cells secrete?

Answer 12

Calcitonin- Ca lowering hormone

Question 13

what epithelium are follicular cells normally?

Answer 13

Simple cuboidal epithelium

Question 14

What happens to thyroid follicle structure when stimulated to release T4/T3

Answer 14

Follicular Cells become columnar and lumen is depleted of colloid

Question 15

What happens to thyroid follicle structure when suppressed

Answer 15

Follicular Cells appear flattened and colloid accumulates in the lumen

Question 16

what is the arterial supply of the thyroid gland

Answer 16

Superior thyroid arteries- supplies anterior and superior portion
Inferior Thyroid arteries- supplies posterior and inferior portion

Question 17

what is the venous drainage of the thyroid gland

Answer 17

venous plexus formed by superior, middle and inferior thyroid vein
Superior + middle- drains into internal jugular vein
Inferior- drains into brachiocephalic vein

Question 18

what regulates thyroid hormone action

Answer 18

hypothalamic- pituitary-thyroid axis

Question 19

what does the hypothalamus secrete and what effect does that hormone have on the anterior pituitary gland

Answer 19

Secretes TRH (thyroid releasing hormone)
TRH acts on thyrotrophs cells in anterior pituitary gland to release TSH (thyroid stimulating hormone)

Question 20

what effect does TSH have on the thyroid gland

Answer 20

TSH acts on the thyroid gland to cause synthesis and secretion of T3/T4

Question 21

what sub-units does TSH have

Answer 21

alpha- same as FSH, LH and HCG

beta- unique

Question 22

how does negative feedback work in TSH secretion?

Answer 22

if T3 and T4 levels high:

T3 and T4 negative feedbacks to hypothalamus and pituitary gland to inhibit TSH production

Question 23

what happens in primary hypothyroidism and give example

primary- problem with main organ

Answer 23

• Underproduction of T3/T4 due to abnormal thyroid gland
• High TSH but low T3/T4
• Hashimoto’s Thyroiditis

Question 24

what happens in secondary hypothyroidism

Answer 24

• Underproduction of T3/T4 due to abnormal anterior pituitary gland
• Low TSH and T3/4
• Sheehan’s syndrome

Question 25

what happens in tertiary hypothyroidism

Answer 25

- Underproduction of T3/T4 due to abnormal hypothalamus - Low T3/T4, variable TSH, Low TRH - RARE

Question 26

what molecule is neccesary for thyroid hormone synthesis

Answer 26

Iodine

Question 27

where is iodine found | how much iodine do our bodies need

Answer 27

seawater, fruit and vegetables | 150-300 ug/day

Question 28

where is iodine deficiency prominent and what does it lead to

Answer 28

high altitudes | leads to endemic goitre (enlarged thyroid)

Question 29

Iodine is reduced to ______ and then absorbed in the _____

Answer 29

Iodide | GI tract

Question 30

Describe the first step in thyroid hormone biosynthesis | Iodine transport

Answer 30

- Iodide transported into the follicular cells by Na/I active transporter against the chemical gradient from the basolateral membrane (energy required) - iodide then diffuses to apex of cells and is transported by the protein- PRENDERIN into vesicles fused with the apical cell membrane

Question 31

Describe the second step in thyroid hormone biosynthesis | organification

Answer 31

- Oxidation of iodide to iodine occurs in the vesicles and it binds to tyrosine residues on Thyroglobulin- in the colloid (this process is called organification and catalysed by the enzyme thyroid peroxidase) - Iodine combines with tyrosine residues on thyroglobulin to form MIT or DIT

Question 32

Describe the third step in thyroid hormone biosynthesis (T3 and T4 formation)

Answer 32

- Peroxidase then combines MIT+ DIT = T3 and DIT+DIT = T4. This takes place within the thyroglobulin proteins * peroxidase is more efficient at combining 2 DIT therefore there is more T4* - Endocytosis of thyroglobulin into follicular cells - The endocytosed thyroglobulin undergoes proteolysis (lysosyme) to release the T4 and T3. - T4 and T3 are transported out of the cell and into the circulation.

Question 33

T_ is more metabolically active than T_

Answer 33

3 | 4

Question 34

T_ released in greater amounts than T_

Answer 34

4 | 3

Question 35

How does T4 become T3

Answer 35

T4 in the periphery undergoes 5'deiodination to form T3

Question 36

how much of circulating thyroxine (T4) is free and bound

Answer 36

Free- 0.5% | Bound- 99.5%

Question 37

what is the importance of free Thyroxine

Answer 37

- Free component is active and regulated, therefore, only free t4 is measured - Bound to thyroid binding globulin, transthyretin and albumin

Question 38

what is the active version of T and what does is bind to

Answer 38

T3 is the active version which binds to nuclear receptors

Question 39

what are the thyroid hormone action on skeletal, cardiovascular and metabolic system

Answer 39

Skeletal: bone turnover Cardiovascular: heart rate Metabolic: lipids and glucose

Question 40

what is the definition of Hyperthyroidism

Answer 40

Condition that occurs due to excessive production of thyroid hormone by thyroid gland

Question 41

what are the causes of hyperthyroidism

Answer 41

– Auto immune- Graves’ disease – Toxic adenoma- benign tumour of thyroid gland – Multinodular goitre- excess production of thyroxine (T4) without requiring stimulation from TSH – Thyroiditis- inflammation of thyroid gland leading to excess production of thyroxine – Excessive administration of thyroxine- use of thyroxine to lose weight

Question 42

what are the clinical features of Graves disease

Answer 42

1) Dysthyroid eye disease/ Graves’ Ophthalmopathy - 50% of patients seen with this - lid retraction and lid lag - pre-orbital oedema (puffy eyes or swelling under eyes) - proptosis (abnormal anterior protrusion of eyes) - diplopia (double vision) - optic nerve compression is rare 2) Dermopathy- Pretibial myxoedema 3) Thyroid acropachy- characterised by soft tissue swelling and finger clubbing

Question 43

what are the clinical features of Hyperthyroidism

Answer 43

``` • Weight loss - Tachycardia • Tremor - Hypertension • Heat intolerance - Palpitations • Diarrhoea - Sweating ```

Question 44

what are the treatment for Hyperthyroidism

Answer 44

Anti-thyroid drugs Radioiodine therapy Surgery

Question 45

what are the anti-thyroid drugs. | describe mechanism of action and adverse effects

Answer 45

1) Carbimazole Inhibits action of thyroid peroxidase enzyme- reduces thyroid hormone production Adverse effects: - Aplasia cutis - Rash - Bone marrow suppression so causes agranulocytosis 2) Propylthiouracil Inhibits thyroid peroxidase Inhibits T4 to T3 conversion watch LFTs

Question 46

How does radioiodine therapy work in treatment for Hyperthyroidism

Answer 46

- Use if beta emission to destroy thyroid tissues

Question 47

what are the side effects of radioiodine therapy

Answer 47

may worsen eye disease - so need steroid cover radiation risk defer conception for 4 months leads to hypothyroidism (main side effect)

Question 48

What is the surgery for Graves disease and what are the complications

Answer 48

``` Removal of thyroid gland Complications: • Haemorrhage • Rec laryngeal palsy- hoarse voice • Permanent hypocalcaemia- damage to parathyroid glands • Hypothyroidism ```

Question 49

what is the definition of hypothyroidism

Answer 49

Condition that occurs due to not enough production of thyroxine by thyroid gland

Question 50

what are the causes of hypothyroidism

Answer 50

Primary- pathology of thyroid gland Severe iodine deficiency Autoimmune thyroiditis (Hashimotos) - Destruction of the thyroid gland (anti TPO antibody) - May be positive family history, more common in females Thyroiditis - Viral and often painful Iatrogenic - Thyroidectomy - Following radio iodine therapy - Drug-induced (Amiodarone, lithium, sunitinib) Secondary- pathology of the pituitary gland Pituitary disease – Secondary hypothyroidism

Question 51

what are the clinical features of hypothyroidism

Answer 51

``` – Depression – Lethargy – Weight gain – Bradycardia – Dry skin – Constipation – Cold intolerance – Poor concentration – Hoarseness – Menorrhagia – Coarse, thin hair – Anaemia – Slow relaxing reflexes – May have goitre ```

Question 52

what is the treatment for hypothyroidism and what are the long-term goals

Answer 52

Levothyroxine - Generally need 1.7-2.0 micrograms / kg /day - Best taken on an empty stomach - Avoid taking with proton pump inhibitors, ferrous sulphate or calcium Long term goals: – Resolve symptoms and normalise TSH – Full suppression of TSH associated with Atrial fibrillation and osteoporosis

Question 53

what are the investigations for hypothyroidism

Answer 53

Measure – Free T4 – TSH • Primary hypothyroidism – High TSH and low T4 • Secondary hypothyroidism – Low TSH and low T4

Question 54

Thyroid cancer has good prognosis if cancer is differentiated. give examples of the differentiated cell

Answer 54

- papillary - follicular - mixed - medullary carcinoma of thyroid

Question 55

thyroid cancer has poorer prognosis if cancer is undifferentiated. give examples of the undifferentiated cell

Answer 55

- anaplastic | - small cell