thyroid gland

Question 1

where does the thyroid gland lie?

Answer 1

lies across trachea at base of larynx, one of larger endocrine glands, (15-20g), but neither visible nor palpable in health.

Question 2

what is synthesised by the thyroid gland?

Answer 2

Synthesises the Thyroid Hormones of which there are two physiologically active forms: T3 (triiodothyronine) and T4 (thyroxine).

Question 3

what two cell types does the thyroid gland contain?

Answer 3

C (clear) cells which secrete calcitonin (Ca2+ regulating hormone).

Follicular cells which support thyroid hormone synthesis and surround hollow follicles.

Question 4

what are thyroid follicles?

Answer 4

spherical structures whose walls are made of follicular cells. Centre of follicle filled with colloid = sticky glycoprotein matrix. Contain 2-3 mths supply of TH.

Question 5

what is the function of follicular cells?

Answer 5

manufacture the enzymes that make thyroid hormones as well as thyroglobulin, a large protein rich in tyrosine residues

Question 6

where are the enzymes from follicular cells released to?

Answer 6

The enzymes and thyroglobulin are secreted from the follicular cells into the colloid.

Question 7

what do follicular cells also actively concentrate?

Answer 7

actively concentrate iodide from the plasma and transport it into the colloid where it combines with the tyrosine residues to form the thyroid hormones.

Question 8

where are both tyrosine and iodine derived from?

Answer 8

diet

Question 9

how does iodide enter follicular cells from plasma?

Answer 9

Iodide enters the follicular cells from the plasma via a Na+/I- transporter (symport). The coupling to Na+ enables the follicular cells to take up iodide against a concentration gradient.

Iodide is then transported into the colloid via the pendrin transporter.

Question 10

what is the role of thyroid peroxidase?

Answer 10

Enzymes exocytosed into the colloid, along with the thyroglobulin, catalyses the oxidation of iodide to iodine and the addition of iodine to tyrosine residues on the thyroglobulin molecule.

Question 11

Addition of one iodine to tyrosine forms?

Answer 11

MIT (monoiodotyrosine)

Question 12

Adding a second iodine forms?

Answer 12

DIT (diiodotyrosine).

Question 13

MIT and DIT then undergo conjugation reactions where…

Answer 13

MIT + DIT → triiodothyronine or T3, or
DIT + DIT→ tetraiodothyronine or Thyroxine T4.

Question 14

what happens in response to TSH?

Answer 14

portions of the colloid are taken back up into the follicular cell by endocytosis. Within the cells they are packaged into vesicles containing proteolytic enzymes that cut the thyroglobulin to release thyroid hormones.

Question 15

describe the mobility of T3 and T4?

Answer 15

Both T3 and T4 are lipid soluble and so pass across the follicular cell membrane into the plasma where they bind to plasma proteins, mainly thyroxine-binding globulin.

Both T3 and T4 circulate in the plasma

Question 16

how do thyroid hormones circulate?

Answer 16

More than 99.8% of T3 and T4 circulates in plasma bound to plasma protein.

Thyroxine Binding Globulin (TBG) has particularly high affinity for T4 releasing it only slowly into the plasma. This partly accounts for the longer half life of T4:
T4 ~ 6 days; T3 ~ 1 day

Only free hormone exerts an inhibitor effect on TSH and TRH.

Only free hormone (0.2% of total plasma TH) is physiologically active.

Question 17

describe differences between T3 and T4?

Answer 17

Most TH circulates in the form of protein bound T4

50x more total (free+bound) T4 in plasma than T3
(~100nmoles/l vs ~2.3nmoles/l respectively)

However 90% of TH binding to TH receptors inside cells is T3.

The TH receptor has a much higher affinity for T3 than T4 making T3 3-5 times more physiologically active than T4

T4 is deiodinated to T3 by deiodinase enzymes. Around half the T4 is deiodinated in plasma, the remaining fraction being deiodinated inside target cells.

Hypothyroid patients are supplemented with T4 yet have normal T3 levels.

Question 18

how is thyroid hormone release regulated?

Answer 18

Question 19

where does thyroid hormone bind to?

Answer 19

TH bind to nuclear receptors in target cells, where they change transcription and translation to alter protein synthesis.

Question 20

what effect does thyroid hormone binding have?

Answer 20

raises metabolic rate and promotes thermogenesis, typically through promoting futile cycles of simultaneous catabolism and anabolism.

increase hepatic gluconeogenesis, although no effect on BG providing pancreas is releasing adequate insulin (therefore not a counter regulatory hormone)

net increase in proteolysis
net increase in lipolysis

critical for growth (lack of TH results in retarded growth)
🡪 stimulates GH receptor expression

essential for brain development in utero (maternal iodine deficiency = congenital hypothyroidism)

Question 21

what are causes of hyperthyroidism?

Answer 21

Graves Disease (common) - antibodies produced that bind mimic TSH and continually activate the thyroid gland. Increased release of TH switches off TSH release from anterior pituitary so [TSH]plasma very low. Thyroid gland may be 2-3x normal size due to hyperplasia. Hyperactivity of cells also apparent.

Thyroid Adenoma (rare ) - hormone-secreting thyroid tumour

Question 22

what are symptons of hyperthyroidism?

Answer 22

1. Increased metabolic rate and heat production
   🡪 weight loss/ heat intolerance
2. Increased protein catabolism
   🡪 muscle weakness/weight loss
3. Altered nervous system function
   🡪 hyperexcitable reflexes and psychological disturbances
4. Elevated cardiovascular function.TH is permissive to epinephrine, β receptors
   🡪 increased HR/contractile force, high output, cardiac failure

Question 23

what are causes of hypothyroidism?

Answer 23

Hashimoto’s Disease - autoimmune attack of thyroid gland most common

Deficiency in dietary iodine – only 50mg/year(!) required but many areas of the world soil has insufficient quantities. Milk, Fish, seafood and seaweed are good sources.

Idiopathic – no known cause, may be linked to thyroiditis.

Question 24

what are symptoms are hypothyroidism?

Answer 24

Decreased metabolic rate and heat production
🡪 weight gain/cold intolerance
2. Disrupted protein synthesis
🡪 brittle nails/thin skin
3. Altered nervous system function
🡪 slow speech/reflexes, fatigue
4. Reduced cardiovascular function
🡪 slow heart rate/weaker pulse

Question 25

what are both hypo and hyperthyroidism often accompanies by?

Answer 25

Both hypo- and hyperthyroidism are often accompanied by significant enlargement of the thyroid gland
Termed goitre

Question 26

what may goitre formation cause?

Answer 26

increased trophic action of TSH on thyroid follicular cells (hypothyroidism) or over-activity as a result of autoimmune disease (Graves Disease)
🡪 results in hypertrophy (overgrowth) of thyroid gland

Question 27

Answer 27

Both examples above are primary (1o) disorders of endocrine hormone release (direct effect on endocrine gland producing end hormone). Secondary (2o) and tertiary (3o) endocrine dysfunction also possible from pituitary and hypothalamic defects respectively.