4.3 - The Thyroid Gland

Question 1

What does the thyroid gland look like?

Answer 1

• butterfly-shaped gland consisting of two lobes (wrap around trachea and connected in the middle by an isthmus)
• pyramidal lobe - extension of thyroid gland (remnant of thyroglossal duct) - 55% of individuals have it
• colloid - sticky mucus extracellular fluid
• follicles are well perfused and surround colloid ECF - follicular cells with colloid in middle
• parafollicular cells release calcitonin, involved in regulation of calcium metabolism

Question 2

Where are the parathyroid glands and what do they do?

Answer 2

• parathyroid glands are embedded in thyroid - they regulate calcium levels in the body through releasing parathyroid hormone (PTH)
• PTH elevates Ca2+ levels by degrading bone and stimulating calcium release = increases body’s ability to absorb calcium from food
• superior and inferior parathyroid glands

Question 3

What does the laryngeal nerve do and how is it significant to the thyroid?

Answer 3

• left recurrent laryngeal nerve runs close and supplies vocal cords
• might get cut during thyroidectomy - damage leads to coarse voice

Question 4

How does the thyroid gland develop?

Answer 4

1. midline outpouching from floor of pharynx (originates from base of tongue)
2. development of thyroglossal duct
3. divides into two lobes
4. duct disappears leaving foramen caecum
5. final position by week 7
6. thyroid gland then develops

Question 5

How does TSH work on the thyroid gland to produce T3 (triiodothyronine) and T4 (thyroxine)?

Answer 5

1. TSH binds to TSH-R on basolateral membrane of follicular cell
2. binding stimulates activation of sodium-iodide cotransporter and Na+ and I- ions get into the cell
3. I- ions move into the colloid where they are oxidised to iodine (iodination)
4. the TSH binding causes production of thyroglobulin (prohormone) which is secreted into the colloid
5. TSH binding also causes activation of TPO (thyroid peroxidase) enzyme which, along with hydrogen peroxide, catalyses all iodination reactions
6. the iodine from before is added to thyroglobulin through iodination which produces MIT + DIT (monoiodotyrosine + diiodotyrosine)
7. a coupling reaction then results in production of T3 and T4 attached to thyroglobulin
8. thyroglobulin is then removed at lysosome and T3 and T4 are released into bloodstream

Question 6

What happens specifically in coupling reactions? (What is MIT and DIT)?

Answer 6

• MIT = 3-monoiodotyrosine
• DIT = 3,5-diiodotyrosine
• coupling of MIT + DIT = T3 (triiodothyronine)
• coupling of DIT + DIT = T4 (tetraiodothyronine = thyroxine)

Question 7

What happens to T4 in target tissues?

Answer 7

• T4 is the main hormone product (prohormone) of the thyroid gland
• deiodinated by deiodinase enzyme to T3 (bioactive form) in target tissues
• also deiodinated in a different position to produce reverse T3 (inactive) - under circumstances requiring reduced metabolism e.g. starvation
• T3 provides almost all the thyroid hormone activity in target cells by entering nucleus and binding to thyroid hormone receptor on thyroid response elements which alters gene expression

Question 8

What % of circulating T3 comes from where?

Answer 8

• 80% from deiodination of T4
• 20% from direct thyroidal secretion

Question 9

How are T3 and T4 transported in blood?

Answer 9

Mostly bound to plasma proteins:

• thyroid binding globulin (TBG): 70-80%
• albumin: 10-15%
• prealbumin (aka transthyretin)
• only 0.05% T4 and 0.5% T3 is unbound (bioactive components)

Question 10

What are the half-lives of T3 and T4?

Answer 10

• T3 –> 2 days
• T4 –> 7-9 days

Question 11

What are some thyroid hormone actions?

Answer 11

• essential for foetal growth and development, especially maturation of the CNS
• increases basal metabolic rate (increases sodium-potassium ATPase, O2 consumption, heat production and BMR)
• protein, carbohydrate and fat metabolism (increases glucose absorption, glycogenolysis, gluconeogenesis, lipolysis, protein synthesis and degradation)
• potentiates actions of catecholamines e.g. tachycardia by increasing cardiac output
• effects on GI (can affect gut transit times), CNS, reproductive systems

Question 12

What does untreated congenital hypothyroidism (undeveloped/poorly controlled thyroid) produce in children?

Answer 12

• cretinism
• TSH measured in new-born infant’s heel-prick test

Question 13

How is thyroid hormone production controlled?

Answer 13

• normal: TRH (hypothalamus) –> TSH (anterior pituitary) –> thyroid –> T3 and T4
• T3 and T4 production has a negative feedback system, where it switches off TRH and TSH production/release in hypothalamus and anterior pituitary
• somatostatin can inhibit production of TSH
• iodide in large quantities can inhibit T3 and T4 production - used clinically if someone has hyperthyroidism - Wolff-Chaikoff effect

Question 14

Are thyroid disorders more common in men or women?

Answer 14

• women (4:1 ratio)
• thyroid disease often caused by autoimmunity, and it is thought that women are more predisposed to autoimmune thyroid disease due to evolution for carrying children - they are exposed to more antigen so more likely to have ‘glitch’ in immune system

Question 15

Is underactive or overactive thyroid gland more common?

Answer 15

• neither, they are both as likely

Question 16

What happens in primary hypothyroidism?

Answer 16

• autoimmune damage to thyroid, causing T4 levels to drop and TSH levels to climb to encounter this
• commonest forms of autoimmune thyroid disease are Hashimoto’s thyroiditis (associated with hypothyroidism) and Graves’ disease (associated with hyperthyroidism)
• presence of one autoimmune disease increases risk of others e.g. those with vitiligo more likely to get autoimmune thyroid disease
• getting a thyroidectomy can also cause hypothyroidism

Question 17

What are symptoms and signs of hypothyroidism?

Answer 17

• deepening voice
• depression and tiredness
• cold intolerance
• weight gain with reduced appetite
• constipation - slower bowels
• bradycardia
• swollen face, swelling of eye socket
• dry and rough skin, muscle cramps
• low sexual desire, menstruation problems
• enlarged thyroid gland
• eventual myxoedema coma - loss of brain function due to severely low thyroid levels

Question 18

What is levothyroxine?

Answer 18

• a drug like T4 that can be used to treat both hypothyroidism and hyperthyroidism (latter through a blocking and replacement regimen)
• doses are adjusted according to TSH and T4 in blood - commonly 100 micrograms and administered orally
• potential complications can be minor e.g. weight loss, headache or major e.g. heart attack, tachycardia (rare as drug well tolerated)

Question 19

Why is liothyronine (T3) not given as a drug and what is combined hormone replacement?

Answer 19

• T3 more expensive than T4 and little evidence that it works better than T4
• combination therapy of both T3 and T4 can be given and some have reported improvement in wellbeing
• however this can be complicated with toxicity symptoms e.g. palpitations, tremor, anxiety
• often combination treatment suppresses TSH

Question 20

What happens in hyperthyroidism?

Answer 20

• thyroid makes too much thyroxine and TSH levels drop
• causes include:
• Grave’s disease - whole gland smoothly enlarged and overactive
• toxic multinodular goitre - multiple nodules which can overproduce thyroid hormone
• solitary toxic nodule - one nodule overproducing thyroid hormone

Question 21

What is Grave’s disease?

Answer 21

• autoimmune disease where antibodies bind to and stimulate TSH receptor in thyroid
• results in smooth goitre
• other antibodies bind to muscles behind the eye = exophthalmos (bulging eyes)
• other antibodies stimulate growth of soft tissue of shins causing pretibial myxoedema - too much glycosaminoglycans in skin

Question 22

What are the symptoms and signs of hyperthyroidism?

Answer 22

• heat intolerance
• weight loss with increased appetite
• myopathy - weakness in muscles
• mood swings, depression, insomnia
• diarrhoea
• tremor of hands
• palpitations
• sore eyes, goitre
• warm, moist skin
• hair loss
• enlarged thyroid gland
• tachycardia, arrhythmia, high BP
• cycle disorders