Thyroid

Question 1

Outline the anatomy of the thyroid gland, including blood supply

Answer 1

Endocrine gland anterior to trachea attached to cartilage - two lateral lobes separated by an isthmus

Highly vascular: superior thyroid artery, inferior thyroid artery and thyroid ima (sometimes)

Question 2

Role of follicular cells?

Answer 2

Accumulate iodine from nearby capillaries and secrete it into the colloid

Question 3

How does iodine get into the follicular cells?

Answer 3

Na/I- symporter on basolateral membrane

Na+/K+ ATPase pumps Na+ back out to maintain gradient for it to keep being symported to amplify I- concentration inside cell = iodine trapping

Question 4

Relevance of basal metabolic rate hormones T4 and T3?

Answer 4

DIT + DIT = T4
DIT + MIT = T3
(Number of iodine molecules)

T4 is main hormone secreted and becomes active T3 once inside tissues (T4 and T3 are iodinated derivatives of tyrosine)

Question 5

Outline 6 steps of thyroid hormone synthesis

Answer 5

1. Thyroglobulin synthesis
2. Uptake of I- (iodide) and concentrate within cell
3. Oxidation of iodide to iodine
4. Iodination of thyroglobulin
5. Coupling of 2 iodinated tyrosine molecules to form MIT and DIT
6. Secretion

Question 6

How is thyroid hormone secretion regulated?

Answer 6

Paraventricular neurones in the hypothalamus releases TRH into bloodstream

Anterior pituitary gland releases TSH (in response to TRH) which acts on thyroid gland to stimulate production and release of T4/T3

Question 7

How are thyroid hormones transported through the body?

Answer 7

Lipophilic so cannot dissolve in blood

Bound to TBG (thyroxin binding globulin, 70%) or Albumin (30%)
TBG has greater affinity for T4
T3/T4 can only enter cells when unbound (free)

Question 8

What are the 3 types of deiodinases and their role?

Answer 8

Deiodinases interconvert T3/T4 to activate or inactivate the hormone

Different types depending on where they’re found:
Type 1: cell surface (T4 to active T3 so can bind to T3R)
Type 2: intracellular (CNS, brown fat, placenta and muscle)
Type 3: T4 into rT3 in placenta and CNS

Question 9

How does T3 enter the cell and what’re its physiological roles?

Answer 9

Via diffusion and MCT8(10) transporter then binds to DNA in nucleus to alter protein synthesis

Metabolism
Maturation and differentiation of cells
Neurological functions
Growth

Question 10

Relevance of Iodine during pregnancy?

What can iodine deficiency in neonates lead to?

Answer 10

At week 12 the thyroid gland makes and secrets T3/T4 under control of foetal hypothalamus but requires Iodine to do so

Cretinism = impaired physical and neurological development (why you do TSH heel prick test at birth)

Question 11

What would the TSH and T4 levels be in hypothyroidism?

Clinical signs and symptoms?

Answer 11

High TSH and low T4 (as TSH should stimulate T4 secretion)

Overweight
Tiredness/fatigue
Mental slowness
Constipation
Dry skin/hair

Question 12

What would TSH and T4 levels be in hyperthyroidism?

Clinical signs and symptoms?

Answer 12

Low TSH and high T4 - excessive metabolic rate

Weight loss
Sweating (heat intolerance) 
Palpitations 
Diarrhoea
Nervousness/irritability
Tiredness

Question 13

What’s a goitre? What’re it’s 3 causes?

Answer 13

Enlarged thyroid gland but doesn’t differentiate between hyper- or hypothyroidism

1. iodine deficiency
2. Graves disease
3. tumour

Question 14

Treatments of thyroid problems?

Answer 14

Hyperthyroid: Carbimazole to inhibit thyroid hormones
Radioactive iodine to destroy gland
Surgery to remove gland
BUT patient will be on levothyroxine for life

Hypothyroid: levothyroxine used to replace T4

Question 15

What 3 hormones does the thyroid gland make and secrete?

Answer 15

T4
T3
Calcitonin (Ca2+ homeostasis)

Question 16

Outline the thyroid gland microstructure

Answer 16

Follicular and parafollicular cells
Colloid in the centre of follicular cells
Lots of nearby capillaries for secretion
Lots of follicles for thyroid hormone storage ready to secrete (follicles actively accumulate iodide from blood and secrete it into the colloid)

Question 17

What’s iodide trapping and why?

Answer 17

Iodide enters follicular cell by Na+/I- symporter on basolateral membrane actively against its gradient = allows thyroid gland to concentrate I- compared to the circulation and is good for using radioactive isotopes to investigate function

Obtain iodine from our diets but it’s rare (most countries supplement salt with it)

Question 18

What are dietary sources of iodine? What does the WHO say

Answer 18

Milk and dairy
Seawater/seafood
Sea salt
Fruit and vegetables (depending on soil)

WHO says iodine deficiency is worlds most prevalent cause of brain damage

Question 19

What’s the metabolic significance of increased T3?

Answer 19

Increase O2 demand/consumption as increased basal metabolic rate

Increased ventilation, CO and substrate conversion

Question 20

What does increased metabolic rate lead to?

Answer 20

Increased CO2, ventilation, urea, renal function
Reduced muscle mass and adipose tissue
Thermogenesis -> sweating, ventilation, surface blood flow

Question 21

What would it indicate if TSH levels were normal but T4 low?

Answer 21

Thyroid hormone resistance - maybe mutation in T3R gene

Question 22

What would it indicate if TSH normals were low and so were T4?

Answer 22

Problem with the anterior pituitary gland = secondary hypothyroidism

Question 23

What’s Graves and Hashimoto’s disease?

Answer 23

Grave’s disease (associated with hyperthyroidism), autoantibody Thyroid Stimulating Immunoglobulin (TSI)

Hashimoto’s associated with hypothyroidism, autoimmune destruction and iodine deficiency