Thyroid Gland Flashcards
Where is the thyroid gland?
When is it usually only visible/ palpable?
- In the neck in front of lower larynx and trachea
- Below thyroid cartilage
When it is enlarged (goitre)
Which 2 nerves are close to the thyroid gland
What do they supply? What action are they involved in>
Recurrent laryngeal nerve
External branch of superior laryngeal nerve
Supply the larynx, are involved in speech
The thyroid gland is highly vascularised. Describe its blood supply
3 arteries supplying it, 3 veins draining it
Superior, middle, inferior arteries and veins
The thyroid gland is a butterfly/ bow tie shape.
Describe its structure
What 2 cell types are found in the thyroid gland?
2 lateral lobes connected by an Isthmus
- Follicular cells
- Parafollicular cells (C cells)
Describe the embryological development of the thyroid gland in 4 steps
(Is 1st endocrine gland to develop)
- At 3-4 weeks, appears as an epithelial proliferation at base of tongue
- Descends as diverticulum through thyroglossal duct
- During migration, remains connected to tongue by thyroglossal duct which then degenerates
- Detached thyroid continues migrating over following 2 weeks
Describe the arrangement of Follicular and Parafollicular cells
Follicular cells are arranged in units called Follicles, separated by connective tissue
Parafollicular cells are found in connective tissue
Outline the structure of the follicles of they thyroid gland
Follicles are ;
- Spherical
- Lined with epithelial (follicular) cells, surrounding a lumen containing Colloid (deposit of Thyroglobulin)
What hormones are made in thyroid gland and from which cell types?
Follicular cells- T3 and T4
Parafollicular cells- Calcitonin
Outline the process in T3 and T4 synthesis in 6 steps
- Iodide is transported into epithelial cells (against a conc. gradient)
- Thyroglobulin (tyrosine rich protein) made in epithelial cells
- Thyroglobulin exocytosed into lumen of follicle
- Iodide oxidised-> Iodinating species
- Iodination of Tyrosine residues in thyroglobulin to form MIT/ DIT (mono-iodotyrosine)
- DIT coupled with MIT/ DIT-> T3/T4
Where and how are T3 and T4 stored?
In lumen of follicles (extracellularly) as part of Thyrogllobulin
(More T4 stored than T3)
Describe the secretion of T3 and T4
Thyroglobulin is taken into epithelial cells from lumen by Endocytosis.
Proteolytic cleavage occurs to release T3 and T4, they diffuse into bloodstream
Thyroid Peroxidase is a membrane bound enzyme that regulates 3 reactions involving Iodide.
What are these 3 reactions?
- Iodine oxidation to iodide (Requires H2O2)
- Iodine addition to tyrosine acceptor residues
- Coupling of MIT or DIT (to form T3/T4 within thyroglobulin)
How much of the body’s iodine is in the thyroid gland?
Via what channel is Iodide taken into epithelial cells from blood?
90-95%
Sodium-iodide symporter
Of T3 and T4, which is secreted more and which has more biological activity
T4 secreted more
T3 has more activity
What is most circulating T3 derived from?
Where does this mostly occur
From T4, occurs in liver and kidneys mostly
How is 4 converted to T3
Removal of the 5’-iodide
What happens if the 3’-iodide is removed from T4?
What is the significance of this?
Inactive reverse T3 is made (rT3)
rT3 can bind to receptors without stimulating them, blocking the effect of T3
What 3 things stimulate the release of TRH from dorsomedial nucleus of hypothalamus
- Circulating T3, T4 levels (negative feedback)
- Stress
- Fall in T\yemperature
TSH from Anterior Pituitary Gland affects which cells of the Thyroid gland?
Follicular cells
Describe the structure of TSH
A glycoprotein composed of 2 non-covalently linked subunits (Alpha and beta)
(Beta provides unique biological activity)
TSH is released in low-amplitude pulses following a diurnal rythm
When are higher and low levels attained?
Higher- During the night
Lower- Early hours of morning
Other than influencing T3 and T4 secretion, how does TSH affect the thyroid gland?
Will the gland be overactive or not?
Trophic effects on gland leading to enlargement;
- Increased vascularity
- Hypertrophy of follicular cells
- Hyperplasia of follicular cells
May/ may not be overactive
T3 and T4 are hydrophobic. How are they transported in the blood?
Transported bound to proteins (Thyroxine Binding Globulin TBG, Albumin and Pre-albumin)
Only a small amount of T3 and T4 are free in solution, and it is this free hormone that is biologically active.
Which hormone has a lower affinity for the transport proteins? How does this affects its half life in circulation?
T3, so has a greater percentage that is free, so has a shorter half-life in circulation (2 days for T3, 8 days for. T4)
Explain how Oestrogens released during pregnancy affect the amount of T3 and T4;
- That is free
- In total in blood
- Oestrogens increase TBG synthesis, so reduced free T3 and T4
- More TRH and TSH made, so more T3 and T4 secreted
- Free T3 and T4 returns to normal
- Total T3 and T4 in blood is increased
List 4 general effects of T3 and T4 on tissues
- Stimulate glucose uptake and metabolism
- Stimulate mobilisation and oxidation of fatty acids
- Stimulate protein metabolism
- Increase metabolic rate (except spleen, testis, brain)
In what 2 ways do T3 and T4 increase the metabolic rate in may tissues (not brain/ testis/ spleen)
- Increased number and size of mitochondria
- Stimulating synthesis of enzymes in respiratory chain
What are the Sympathomimetic effects of T3 and T4?
Increase target cell response to Catecholamines by increasing receptor number on target cells
What are the specific effects of T3 and T4 on the;
- Cardiovascular system
- Nervous system
- GI system
(They stimulate hormone and neurotransmitter receptor synthesis)
Cardio;
- Increase in HR and Inotropy (Increased synthesis of heart muscle protein)
Nervous;
- Increased myelination of nerves and neuron development
GI;
- Increased motility
How do T3 and T4 act on the cells to affect gene transcription and produce it’s desired cellular response
- Crosses plasma membrane, enters nucleus and binds to Thyroid Hormone Receptor on DNA
- The binding inhibits Repression of Gene Transcription, so the gene can now be expressed
- New protein mediates the effects of the hormone
State, in Molarity, the normal plasma levels of;
- Free T4
- Free T3
- TSH
fT4: 10-25 pM
fT3: 3-8 pM
TSH: 1-15 pM
Goitre (enlargement of thyroid gland) may be due to either Hypo/ Hyperthyroidism, but isn’t always present in either)
When does it develop?
Develops when thyroid gland is overstimulated
List 7 causes of Hypothyroidism
- Thyroid gland failure
- TSH/ TRH deficiency
- Insufficient intake of Iodine
- Surgery
- Anti thyroid drugs
- Radioactive iodine
- Automimmunity
List 10 general symptoms of Hypothyroidism
- Weight gain
- Lethargy
- Intolerance to cold
- Bradycardia
- Dry skin
- Alopecia (hair loss)
- Hoarse voice
- Slow reflexes
- Constipation
- Reduced BMR
State the levels of T3, T4 and TSH in Hypothyroidism
Low T3 and T4
Elevated TSH
What is Cretinism?
What are 2 physical features
Congenital hypothyroidism in infants (can be caused by iodine deficiency during pregnancy)
- Dwarfed stature
- Poor bone development
What is Myxedema?
What is 1 physical feature
Severely advanced hypothyroidism in adults
- Thick puffy skin
What disease is the most common form of Hypothyroidism, and also the most common thyroid gland disease?
How is it treated?
Hashimoto’s disease (autoimmune)
Treated with Oral Thyroxine (T4 used since longer half life)
Describe the 2 possible pathologies of Hashimoto’s disease
- Results in destruction of thyroid follicles
- Produces an antibody that blocks the TSH receptor on follicular cells
How many weeks does it take for blood tests to normalise after treatment of Hashimoto’s with Oral Thyroxine?
6-8 weeks
List 6 causes of Hyperthyroidism other than stress
- Autoimmune (Grave’s)
- Toxic multinodular goitre
- Toxic adenoma
- Excessive T3/ T4 therapy
- Drugs (Amiodarone can also cause Hypo)
- Ectopic thyroid tissue (not in normal place)
List 10 general symptoms of Hyperthyroidism
- Weight loss
- Fatigue, weakness
- Heat intolerance
- Tachycardia
- Increased motility and appetite
- Tremor of outstretched hands
- Breathlessness
- Sweating
- Increased BMR
- Osteoporosis
Other than goitre name a physical feature that sometimes appears in hyperthyroidism
Bulging Eyes (Exopthalmos)
What are 3 ways of treating Hyperthyroidism
- Antithyroid drugs
- Surgical reduction of gland
- Radioactive iodine (destroys part of gland)
What is the most common form of Hyperthyroidism?
Grave’s disease (affects mostly women)
State the levels of T3, T4 and TSH in Hyperthyroidism
High T3 and T4
Low TSH
Describe the Pathology of Grave’s disease
Why is T3 and T4 hormone secretion not affected by the drop in TSH?
Autoimmune disease in which antibodies (TSI) are made that stimulate TSH receptors on follicular cells
T3 and T4 release is stimulated by TSI (Thyroid stimulating immunoglobulin), rather than TSH
What is the most commonly Antithyroid drug used in the UK?
How does it work?
Carbimazole
Inhibits Thyroid Peroxidase, preventing coupling and iodination of tyrosine residues on thyroglobulin
(Blocks formation of T3 and T4)
Carbimazole is a Pro-drug. What is it converted to in the body?
Methimazole
What substance is used for isotope scanning of the thyroid with a gamma camera (Scintigraphy)
Why does it have low radiation exposure
Technetium-99m (most commonly used medical radioisotope)
Short half life of only 1 day
Other than Thyroid Scintigraphy, what are 3 uses of Technetium-99m?
- Bone scan
- Brain imaging
- Myocardial perfusion imaging
State the free plasma T3, T4 and TSH levels of Sub-clinical hyperthyroidism
Normal T3 and T4
Undetectable TSH
What does dietary iodine deficiency always result in?
Goitre
What is the commonest cause of Goitre on a global basis?
What is the commonest cause of Goitre in the UK?
Global: Iodine deficiency
UK: Multinodular goitre
