L5 Thyroid gland

Question 0

Anatomy of thyroid glands

Answer 0

• comprises left and right lobes connected by isthmus
• forms from floor of pharynx
• 20gm in weight and there is a rich blood supply: 5ml/gm/min
• follicles are where thyroid hormones are produced

Question 1

How do you diagnose thyroid disease?

Answer 1

• by measuring plasma levels of total and free T3, T4 (TSH reference level= 0.4-0.5mlU/L)
• by performing thyroid function tests: TRH challenge test (basal level of TSH is noted and retest the TSH level after TRH has been released) and thyroid radioactive iodine uptake
• by performing a thyroid exam; imaging

Question 2

What is the appearance for active thyroid gland cells?

Answer 2

• follicle: the flattened cuboidal cells transform into columnar
• there is a reduction of colloid = being utilised
• parafollicular cells are endocrine cells found between the follicles which do not produce T3/T4

Question 3

How are thyroid being synthesised?

Answer 3

1) iodide is taken into cells via Na-iodide transporter. Iodide is oxdises into iodine and pump into the colloid space. Thyroglobulin binds to iodine (which is a store of tyrosine molecules)
2) enzyme thyroid peroxidase causes: iodination of tyrosines on thyroglobulin (also known as “organification of iodide”) & synthesis of thyroxine or triiodothyronine from two iodotyrosines.
3) thyroid hormones are released from the colloid by: thyroid epithelial cells ingest colloid by endocytosis from their apical borders (where thyroid hormones are made)
Colloid-laden endosomes fuse with lysosomes, which contain hydrolytic enzymes that digest thyroglobluin, thereby liberating free thyroid hormones.
Finally, free thyroid hormones apparently diffuse out of lysosomes, through the basal plasma membrane of the cell, and into blood where they quickly bind to carrier proteins for transport to target cells.

Question 4

How do you form a T3 and a T4 molecule?

Answer 4

• T3= MIT + DIT
• T4= DIT + DIT
• DIT= di-iodinated-tyrosine
• MIT= mono-iodinated-tyrosine

Question 5

Uptake of iodide

Answer 5

• requires adequate dietary iodine = >75 microgram/day
• iodide are very efficiently absorbed= only 15 microgram is lost from gut per day
• absorbed iodide first enters the extracellular pool(150 microgram)
• removed from extracellular pool by thyroid or kidneys
• kidneys excrete 485 microgram per day
• thyroid takes up 115 microgram per day by active transport. It loses 40 microgram as recycled free iodide and 75microgram as T3/T4
• thyroid contains huge iodide store in colloid
• healthy suggest ingest 500 microgram iodine per day

Question 6

How are thyroglobulin reabsorbed?

Answer 6

• MIT and DIT are broken down by iodotyrosine deiodinase to give free iodide (recycled)

Question 7

How are T3 and T4 secreted from the colloid?

Answer 7

• lysosomes containing protease attach to resorbed droplets and digest colloid
• T4: 70 microgram/day; T3: 5 microgram/day and reverse T3: less than 5 microgram/ day are liberated and released into blood

Question 8

What is reverse T3?

Answer 8

(order is crucial here)

• T3: MIT + DIT
• reversed T3: DIT + MIT

Question 9

What is the plasma level of T4 and T3( tri-iodothyronine)?

Answer 9

• T4: 0.08 microgram/ml ; T3: 0.001 microgram/ml
• Because the bioactivity of T3 is higher than T4 (more potent) so there is a lower level of T3
• Reversed T3 rapidly excreted and T3 is lost by further de-iodination and excretion. Some T4 lost by deamination while most are metabolised by de-iodinated to T3 & reverse T3

Question 10

How are T3 and T4 exert effects on our body cells?

Answer 10

*By influencing nuclear receptors on cells that regulate gene transcription

1) increase transcription of NA/K ATPase = increases basal metabolic rate and oxygen consumption= thermogenesis
2) beta adrenoreceptor is regulated by T3 = increase in expression due to T3 presence= increase heart rate, CO, muscle contraction
3) increase synthesis of growth hormones
4) increase development for nervous system
5) increase gut motility and reproduction

• only the free flowing T4 can have actions on receptors, ie most T4 are protein bound = can cause effects

Question 11

What is the conventional test for thyroid level in blood?

Answer 11

• By measuring the TSH level in blood

Question 12

What is the sign to show thyroid problem?

Answer 12

• goitre, it can present in hypo or hyperthyroidism

eg hyperthyrodism, hashimoto’s thyroditis, iodine deficiency disorder

Question 13

Incidence of thyroid diseases in the uk

Answer 13

• higher incidence in women than men

Question 14

Hypothyroidism in early development

Answer 14

• neurological deficits (mental retardation)
• small stature and immature appearance
• puffy hands & face
• delayed puberty
• there is neonatal screening for TSH and T4 level

Question 15

Hypothyroidism in adulthood

Answer 15

• insidious onset: usually due to blockage of thyroid receptors by antibiotics= autoimmune
• Low BMR and cold sensitivity
• slow, hoarse speech
• weight gain
• constipation
• bradycardia
• basically all systems being slowed

Question 16

What are the causes of hypothyroidism?

Answer 16

• chronic autoimmune thyroiditis caused by antibody production against thyroglobulin or thyroid tissue (hashimoto’s thyroditis)
• thyroid radiation
• iodide deficiency
• pituitary/ hypothalamus defect

Question 17

What is the treatment for hypothyroidism?

Answer 17

• replacement therapy with T4 thyroxine with careful management of doses (can go over-board)

Question 18

What are the signs of hyperthyroidism?

Answer 18

• basically everything sped up
• tachycardia; palpitation
• increases BMR and raised body temp
• nervousness, restlessness, tremors, anxiety
• increase appetite but associate with weight loss
• tiredness
• increase bowel movement

Question 19

What is the most common type of hyperthyroidism?

Answer 19

• Grave’s disease, aka diffuse toxic goitre

- critical sign: exopthalmos = bulging eyes

Question 20

What are the causes of hyperthyroidism?

Answer 20

1) Grave’s disease: Autoimmune response which stimulate TSH receptor by auto-antibodies chronically activate tyroid gland
2) toxic multinodular goitre
3) toxic adenoma (in thyroid)
4) pituitary tumour (so producing TSH)

Question 21

What are the treatments for hyperthyroidism?

Answer 21

• Antithyroid drugs: thiocarbamides, eg. carbimazole, propylthiouracil, methimazole or propanolol (to reduce CVS effect)
• Radioactive iodine (thyroid irradiation)
• surgery but rarely used except for malignancy due to the proximity with recurrent laryngeal nerve

Question 22

What is the differentiation between T3 and T4?

Answer 22

• The major secreted product of the thyroid gland is T4 while T3 is secreted only in small amounts and derives mainly from the peripheral deiodination of T4. One third of circulating T4 is converted to T3 in peripheral tissues by deamination. Both hormones are present in serum either bound to proteins or in the free state. T3 is less tightly bound to plasma proteins than is T4 and is therefore more readily available for cellular uptake. The free hormone is biologically active and interacts with specific receptors localized in the membrane, mitochondria, cytoplasm and nucleus of responsive cells. T3 binds to nuclear receptors to a much greater extent than T4, hence T3 is more rapidly and biologically active than T4. T3 and T4 are deiodinated and deaminated in the tissues. In the liver, they are conjugated, pass into the bile and are excreted into the intestine. Conjugated and free hormones are also excreted by the kidney.

Question 23

How can you increase the production of T3 & T4?

Answer 23

• pituitary gland produces TSH which binds to follicle cells and increases production of T3 & T4

Question 24

Summary of thyroid hormones

Answer 24

1. the major source of circulating T3 is not from thyroid secretion, but from peripheral deiodination of T4;
2. the negative feedback at the pituitary anterior lobe is principally through T4 taken from the circulation and converted in the thyrotrope to T3 by thyrotrope deiodinase;
3. the peripheral deiodination depends on the physiological state of the organism. It allows an autonomy of response of the tissues to the hormones. Deiodination can convert T4 (a less active hormone) to T3 (a more active hormone) or not. The conversion depends on activities of the various deiodinating enzymes.