thyroid gland Flashcards
where does the thyroid gland lie?
lies across trachea at base of larynx, one of larger endocrine glands, (15-20g), but neither visible nor palpable in health.
what is synthesised by the thyroid gland?
Synthesises the Thyroid Hormones of which there are two physiologically active forms: T3 (triiodothyronine) and T4 (thyroxine).
what two cell types does the thyroid gland contain?
C (clear) cells which secrete calcitonin (Ca2+ regulating hormone).
Follicular cells which support thyroid hormone synthesis and surround hollow follicles.
what are thyroid follicles?
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.
what is the function of follicular cells?
manufacture the enzymes that make thyroid hormones as well as thyroglobulin, a large protein rich in tyrosine residues
where are the enzymes from follicular cells released to?
The enzymes and thyroglobulin are secreted from the follicular cells into the colloid.
what do follicular cells also actively concentrate?
actively concentrate iodide from the plasma and transport it into the colloid where it combines with the tyrosine residues to form the thyroid hormones.
where are both tyrosine and iodine derived from?
diet
how does iodide enter follicular cells from plasma?
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.
what is the role of thyroid peroxidase?
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.
Addition of one iodine to tyrosine forms?
MIT (monoiodotyrosine)
Adding a second iodine forms?
DIT (diiodotyrosine).
MIT and DIT then undergo conjugation reactions where…
MIT + DIT → triiodothyronine or T3, or
DIT + DIT→ tetraiodothyronine or Thyroxine T4.
what happens in response to TSH?
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.
describe the mobility of T3 and T4?
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
how do thyroid hormones circulate?
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.
describe differences between T3 and T4?
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.
how is thyroid hormone release regulated?
where does thyroid hormone bind to?
TH bind to nuclear receptors in target cells, where they change transcription and translation to alter protein synthesis.
what effect does thyroid hormone binding have?
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)
what are causes of hyperthyroidism?
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
what are symptons of hyperthyroidism?
- Increased metabolic rate and heat production
🡪 weight loss/ heat intolerance - Increased protein catabolism
🡪 muscle weakness/weight loss - Altered nervous system function
🡪 hyperexcitable reflexes and psychological disturbances - Elevated cardiovascular function.TH is permissive to epinephrine, β receptors
🡪 increased HR/contractile force, high output, cardiac failure
what are causes of hypothyroidism?
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.
what are symptoms are hypothyroidism?
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
what are both hypo and hyperthyroidism often accompanies by?
Both hypo- and hyperthyroidism are often accompanied by significant enlargement of the thyroid gland
Termed goitre
what may goitre formation cause?
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
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.
