Thyroid Gland Flashcards by Ronit Hardasani

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)

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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

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The thyroid gland is highly vascularised. Describe its blood supply

3 arteries supplying it, 3 veins draining it

Superior, middle, inferior arteries and veins

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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)

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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

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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

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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)

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What hormones are made in thyroid gland and from which cell types?

Follicular cells- T3 and T4

Parafollicular cells- Calcitonin

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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

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Where and how are T3 and T4 stored?

In lumen of follicles (extracellularly) as part of Thyrogllobulin

(More T4 stored than T3)

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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

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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)

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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

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Of T3 and T4, which is secreted more and which has more biological activity

T4 secreted more

T3 has more activity

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What is most circulating T3 derived from?

Where does this mostly occur

From T4, occurs in liver and kidneys mostly

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How is 4 converted to T3

Removal of the 5’-iodide

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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

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What 3 things stimulate the release of TRH from dorsomedial nucleus of hypothalamus

Circulating T3, T4 levels (negative feedback)
Stress
Fall in T\yemperature

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TSH from Anterior Pituitary Gland affects which cells of the Thyroid gland?

Follicular cells

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Describe the structure of TSH

A glycoprotein composed of 2 non-covalently linked subunits (Alpha and beta)

(Beta provides unique biological activity)

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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

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Other than influencing T3 and T4 secretion, how does TSH affect the thyroid gland?

Will the gland be overactive or not?

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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?

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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?

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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

1. Crosses plasma membrane, enters nucleus and binds to Thyroid Hormone Receptor on DNA 2. The binding inhibits Repression of Gene Transcription, so the gene can now be expressed 3. 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

Thyroid Gland Flashcards

(54 cards)