Lecture 17: Thyroid

Question 1

Role of thyroid hormones?

Answer 1

• Important for growth and development - particulary fetal
• Maintian metabolic activity and oxygen requirements - particularly the brain
• Regulates lipid and carbohydrate metabolism and thus body weight

Question 2

Embryological beginnings? clinical points?

Answer 2

Starts from endodermal tissue at the back of the tongue at week 4

Thyroglossal duct breaks down and gland descends to the front of the trachea. By week 12-20 it becomes functional but only by week 20-26 does it function independent of the mothers thyroid.

Failure to migrate = lingual thryoid

Remnints of the thyroglossal cyst - lump at front of neck moves up when you poke tongue out

Question 3

Clinical anatomy of the thyroid?

Answer 3

Found:

• Deep to sterno-hyoid muscle
• Lying posterior is the recurrent laryngeal nerve and tracheal ring 2 and 3
• The oesaohagus is found on the left
• The superior thyroid artery (from ext carotid) and inferior thyroid artery (from subclavian)
• Superior and middle thyroid vein drain into the internal jugular vein and the inferior thyroid vein into the breachiocephalic vein.
• Innervated by ANS

Question 4

Histological appearance and function?

Answer 4

Filled with gooey substance called Thyroglobulin formed in the thyroid follicular cells and is where thryoid hormone is stored and manufactured.

• Thyroglobulin circulates in the body in low levels and is elevated in inflammatory conditons.
• Most importantly used as a follow up for checking that the entire thryoid has been removed.

Parafollicular cells produce Calcitonin

• unknown function
• used as a marker to see if thryoid has been removed in medullary thryoid cancer (a cancer of the parafollicular cells)

Question 5

Dietary Iodine? Whas gud?

Answer 5

Iodine is needed in relatively low amounts but NZ has low iodine soil and people are using less salt so we still battle a little.

Leads to:

• compensatory enlargement of the thyroid (endemic goitre)
• if in pregnancy - fetal thyroid levels low causing irreversible damage to the developing CNS = Cretinism

Question 6

Thryoid hormone synthesis? Transport?

Answer 6

Iodine is extremely low in the plasma and so iodine is trapped by a sodium-iodine symporter (NIS)

• Active transport of two Na ions results in the entry of one I molecule.
• Thyroid gland contains about 50days worth of iodine

NIS found: clinical point for radioactive iodine

• breast
• gastric mucosa
• ciliary body of eye
• Salivary gland
• differentiated thyroid cancer cells (radioactive iodine treatment works well)

Question 7

Path of iodine from capillaries to colloid?

Answer 7

1. Transported into the cell via NIS
2. is oxidised by (thyroid) peroxidase**
3. Enters the colloid as thryoglobulin (MIT and DIT)
4. T3 an T4 thyroglobulin is made (mostly DIT x2 = T4)

WHEN IODINE IS NEEDED

1. thyroglobulin is endocytosed (colloid drops)
2. Protease peptidase causes T3 and T4 to be released where it travels into the blood
3. MIT and DIT are recycled

** - This enzyme is what has antibodies against it in autoimmune conditions against the thryoid, ALSO, carbemazol is a drug used to interfer with this enzyme to decrease thryoid hormone.

Question 8

Storage and relese of thyroid hormone?

Answer 8

Large store of thyroid hormone (T4/3) incorporated into Tg

Release of large amounts of preformed thyroid occur in inflammatory conditions - Thyroiditis and become thyrotoxic and then spontaneously return to normal before going hypothyroid as the thyroid takes a while to become active again.

80% of thryoid hormone released is T4 is the form binding to receptors in the periphery and converting to T3 (the active form the body sees)

Question 9

TSH? Feedback?

Answer 9

Thyroid stimulatimg hormone released from the pituitary

• has an A subunit the same as LH, FSH, TSH, HCG
• B subunit cofers receptor specificity
• HCG in pregnancy will stimulate the thyroid and so TSH will be slightly lower in the first trimester

T3 and T4 both have negative feedback on the hypothalamus and particularly the pituitary. There is a range of what peoples normal level is kept aroud.

Question 10

Stimulation of TSH? Clinical importance?

Answer 10

• Increase in iodine into follicular lumen
• Increases blood flow to the thryoid
• increases in Tg, TPO and H₂O₂
• increases endocytosis and degradation of Tg
• increased T4 release

Graves disease: self-immune condition where patients have antibodies to the TSH receptor.

Question 11

Peripheral metabolism of thyroid hormones?

Answer 11

T4 is the main thyroid hormone in plasma

T3 is also released and is generated by peripheral metabolism from T4 by removal of a single iodine atom.

Question 12

Thyrotoxicosis? Symptoms and signs?

Answer 12

Low TSH, High T4 and T3

Symptoms:

• nervousness, increased sweating
• psychiatric disorders
• Weight loss - despite increased apetite
• Heat sensitivity - from BV dilation
• tachycardia - AF and heart palpatations
• weakness - profound

Signs:

• Bruit/noise over thyroid and tachycardia
• Goitre
• Skin changes
• Tremor
• Eye signs

(in asain and maori men there is thought to be a chanelopathy that leads to severe hypokalaemia and bouts of paralysis as a result of this)

Question 13

Some causes of thyrotoxicosis?

Answer 13

1. Graves disease - autoimmune production of antibody that stimuates TSH receptor
2. Multinodular goitre: Hyperfunctioning regions of thyroid gland, no supressed by circulating thryoid hormone
3. Thyroiditis
4. Drugs - amiodarone, iodine, thyroxine
5. Toxic nodule

Question 14

Primary hypothyroidism?

Answer 14

High TSH, Low T4, +ve TPO antibodies = Hashimoto’s disease

• Adult onset is slow
• can effect all organ systems
• Decrease in energy metabolism - low basal metabolic rate +/- slightly low body temperature
• decreased proten synthesis.

Presents as:

• weight gain, cold, hair loss, dry skin, constipation, tired, oedema

Question 15

Eye signs of thryoid disease?

Answer 15

GAGs infiltrate behind the eye and cause eyelid retraction and redness of eyes.