14.1 - Thyroid Gland Flashcards

1
Q

Structure and placement of the thyroid gland

A
  • Lies against and around front of larynx + trachea
  • Thyroid glands situated just above cricoid cartilage and below the thyroid cartilage
  • There is a right and a left lobe of the thyroid, and joined by a structure called isthmus
  • Isthmus extends from 2nd to 3rd rings of trachea
  • Found near C7 of the spine
  • ‘bow tie’ shape and location
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2
Q

Embryological development of thyroid gland

A
  • First endocrine gland to develop
  • 3-4 weeks gestation it appears as an epithelial proliferation at base of tongue (floor of pharynx)
  • Takes several weeks to migrate into final position
  • Descends through thyroglossal duct and migrates downwards in front of hyoid bone
  • During migration remains connected to tongue by thyroglossal duct which then degenerates
  • Detached thyroid then continues to final position
  • If migration doesn’t occur as normal, thyroid will be in different place
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3
Q

Histology points of thyroid tissue

A
  • Follicular cells arranged in spheres called thyroid follicles
  • Follicles filled with colloid
  • Colloid is a deposit of thyroglobulin
  • Thyroglobulin is where thyroid hormone is sythesised
  • Colloid is extracellular (even though it is inside follicle)
  • Thyroid gland also contains larger parafollicular cells. These don’t form spheres of colloid. These produce calcitonin
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4
Q

How are thyroid hormones produced

A
  • Produced on protein called thyroglobulin
  • Thyroid hormones derived from tyrosine residues that are iodinated (ie have iodines added)
  • Tyrosine residues within thyroglobulin undergo iodination (either one or two iodines are added)…
    ☞ 1 iodine added = monoiodotyrosine (MIT)
    ☞ 2 iodines added = diiodotyrosine (DIT)
  • Coupling of MIT + DIT = T3 or DIT + DIT = T4
  • Thyroid peroxidase is vital for this process (different card)
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5
Q

What do T3 + T4 consist of (how they are produced on different card)

A

T3 aka triiodothyronine is made of one MIT and one DIT coupled together
T4 aka tetraiodothyroinine aka thyroxine is made of two DIT coupled together

T3 + T4 are thyroid hormones

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6
Q

Thyroglobulin

A
  • Produced by parafollicular cells
  • Acts as a scaffold on which thyroid hormones are formed
  • Contains many tyrosine molecules (which are needed for thyroid hormone synthesis)
  • Only a handful of these are used to synthesise T3 + T4
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7
Q

What does thyroid peroxidase do

A
  • Multipurpose enzyme involved in thyroid hormone synthesis
  • oxidation of iodide (present in cells) → iodine, requiring the presence of H2O2
  • iodination where iodine is added to a tyrosine residue on thyroglobulin protein
  • coupling of MIT or DIT to generate thyroid hormones within thyroglobulin
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8
Q

Dietary iodine

A
  • Dietary iodine reduced → iodide before absorbtion, so that it can be stored in cells. This reduction occurs in small intestine
  • Iodide is oxidised back to iodine when it needs to be used by thyroglobulin + thyroid peroxidase
  • Thyroid hormones and precursors are the only molecules in human body that contain iodine
  • Iodide is taken up from blood by thyroid epithelial cells that have a sodium-iodide symporter aka iodine trap
  • Dietary sources of iodine are mainly near sea (eg crops grown near sea) and seaweed
  • Also found in dairy, grains, meat and some in veg + egg. Iodized salt is best source
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9
Q

Why is most T4 is converted to T3 outside thyroid

A
  • The main product from the thyroid gland is T4 but T3 has much more biological activity
  • Most T4 → T3 in the liver and kidneys
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10
Q

How are T3 + T4 transported around the body

A
  • These hormones are lipid soluble
  • Therefore cannot be easily transported around in aqueous environment
  • Transported in blood bound to the protein thyroxine-binding globulin
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11
Q

Regulation of thyroid hormone

A

hypothalamus releases TRH → causes anterior pituitary to release TSH → TSH stimulates thyroid gland to produce thyroid hormone (T3 + T4) → thyroid hormone has affects on target tissues

Regulated by negative feedback
☞ thyroid hormone has negative (inhibiting) effect on anterior pituitary + hypothalamus via long loop
☞ TSH has negative effect on hypothalamus via short loop feedback

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12
Q

What does thyroid hormone have an effect on

A
  • Thyroid hormone = T3 + T4
  • Effect virtually every cell in the body
  • More general effects rather than specific
  • Two main interconnected responses:
    ☞ metabolism
    ☞ growth and development
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13
Q

Thyroid stimulating hormone (TSH) + what does it stimulate

A
  • Glycoprotein hormone composed of 2 non-covalently bound subunits
  • Consists of an α and a β subunit
  • Triggers intracellular signalling pathways → **thyroid gland stimulated to produce thyroid hormones… therefore
    ☞ iodide uptake
    ☞ iodide oxidation
    ☞ thyroglobin synthesis
    ☞ thyroglobulin iodination
    ☞ colloid pinocytosis into cell
    ☞ proteolysis of thyroglobulin
    ☞ cell metabolism and growth
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14
Q

What differentiates LH, FSH and TSH from each other

A

They all have two subunits:
- α subunit all the same present in all three
- β subunit differs between them and provides unique biological activity

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15
Q

What is another name for T4 hormone

A

thyroxine

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16
Q

What type of receptor is a TSH receptor

A
  • G-protein coupled receptor
  • Promiscuous (can couple to either Gαs or Gαq)
  • Gαs has positive effect on adenylyl cyclase → cAMP → protein kinase A → stimulation of thyroid hormone synthesis + release
  • Gαq has positive effect on phospholipase C → DAG and IP3 → Ca2+ release via IP3 receptor and PKC activation → stimulation of thyroid hormone synthesis + release
17
Q

General metabolic actions of thyroid hormone

A

increase in basal metabolic rate and heat production
- In most tissues (except brain, spleen and testis)
- Stimulate metabolic rate by increasing number and size of mitochondria, and stimulating synthesis of enzymes in respiratory chain
stimulation of metabolic pathways
- Mainly catabolic pathways stimulated (eg production and mobilisation of energy resources)
- lipid: stimulates lipolysis and β oxidation of fatty acids (using up fatty acids)
- carbohydrate: stimulate insulin dependent glucose entry into cell and increase gluconeogenesis + glycogenolysis
sympathomimetic effects
- Similar effect to stimulation of sympathetic NS
- Increase catecholamine receptor numbers
- Therefore increases cell sensitivity to adrenaline/noradrenaline etc

18
Q

Tissue-specific effects of thyroid hormone

A

cardiovascular system
- Increases heart response to catecholamines (adrenaline + noradrenaline)
- Increase cardiac output by increasing heart rate and force of contraction
- Peripheral vasodilation to carry extra heat to body surface
nervous system
- Increases myelination of nerves and development of neurones

19
Q

What are thyroid hormone receptors

A
  • Member of nuclear receptor family
  • Function as a hormone-activated transcription factor
  • Act by modulating gene expression
  • Thyroid hormone receptors bind to DNA in absence of hormone, leading to transcriptional repression
  • Hormone binding is associated with conformational change → activates gene transcription
  • Thyroid hormone is lipid soluble so can enter cell through thyroid hormone transporters
  • Once in cytoplasm, diffuses through nuclear pore
  • Once in nucleus, can bind to thyroid hormone receptor that is already bound to TRE (thyroid response element) on DNA
  • Binding relieves repression of gene transcription and gene is now expressed
  • Expression of new protein mediates effect of thyroid hormone
20
Q

Some other examples of thyroid hormone activated genes

A
  • PEPCK
  • Ca2+ ATPase
  • Sodium-potassium pump
  • Cytochrome oxidase
  • 6-phosphogluconate dehydrogenase
21
Q

What could be some causes of variations in free T3 and T4 levels and TSH levels in blood, unrelated to thyroid disease

A

T3 + T4: methodological factors, albumin changes and dilution effects
TSH: dinural variation, pulsatile secretion and medications

22
Q

Why would TSH be very low/undetectable in hyperthyroidism

A

Because TSH would be supressed by negative feedback mechanisms by too much thyroid hormone being produced
☞ but in conditions like Graves’ disease, production of Thyroid stimulating immunoglobulin (TSI) continually stimulates thyroid hormone secretion outside normal negative feedback control. Therefore thyroid levels still high even when TSH is supressed.

23
Q

What is goitre

A
  • enlargement of the thyroid gland
  • May accompany either hypo or hyperthyroidism
  • Develops when the thyroid gland is overstimulated
  • Suggests dysfunction, but doesn’t say the source of the dysfunction
24
Q

Hypothyroidism clinical signs + general symptoms

A
  • Obesity
  • Lethargy
  • Intolerance to cold
  • Bradycardia
  • Dry skin
  • Alopecia
  • Hoarse voice
  • Constipation
  • Slow reflexes

Low T3 and T4, elevated TSH

25
Q

Some causes of hypothyroidism

A
  • Faliure of thyroid gland
  • TSH or TRH deficiency
  • Inadequate dietary supply of iodine
  • Radioactive iodine (can be used for thyroid imaging)
  • Autoimmunity (eg Hashimotos)
  • Post surgery
  • Congenital
  • Anti-thyroid drugs
26
Q

What is cretinism

A
  • Hypothyroidism in kids
  • Due to iodine deficiency in infancy
  • Nervous system doesn’t develop properly
  • Dwarfed stature
  • Mental deficiency
  • Poor bone development
  • Slow pulse
  • Muscle weakness
  • GI problems
27
Q

What is the general meaning of the word myxedema

A
  • Hypothyroidism in adults
  • Thick, puffy skin
  • Slow speech
  • Mental deterioration
  • Intolerance to cold

Note: different to term ‘pre fibial myxedema’ which describes changes to skin that occur in hyperthyroidism and depositions of glycoproteins in skin that give a waxy appearance

28
Q

What are clinical signs + symptoms of hashimoto

A
  • Hypothyroidism
  • Goitre
  • Fatigue
  • Increased sensitivity to cold
  • Dry skin
  • Constipation
  • Muscle weakness, aches, tenderness and stiffness
    low T3 + T4 and elevated TSH
29
Q

What is hashimoto’s and how is it treated

A
  • Hypothyroidism
  • Autoimmune disease resulting in destruction of thyroid follicles
  • Most common disease of thyroid glands
  • Much more common in women than men
    treatment
  • Oral thyroid hormone
  • T4 is used due to its longer half-life
  • Normally 50-200 μg/day
30
Q

Hyperthyroidism symptoms + signs

A
  • Goitre (some cases)
  • Exophthalmos aka bulging eyes (some cases)
  • Weight loss (due to increased metabolic rate)
  • Irritability
  • Heat intolerance, sweating and warm hands
  • Tachycardia + arrythmia
  • Fatigue + weakness
  • Increased bowel movements – increased appetite
  • Tremor
  • Hyper-reflexive
  • Breathlessness
  • Loss of libido
31
Q

Causes of hyperthyroidism

A
  • Autoimmune (Graves’ disease)
  • Toxic multi-nodular goitre
  • Toxic adenoma
  • Excessive thyroid hormone therapy
  • Drugs eg amiodarone
  • Ectopic thyroid tissue (extra thyroid tissue produced during embryological development)
32
Q

Signs + symptoms of grave’s disease

A
  • Increase in BMR
  • Excessive sweating
  • Decrease in body weight
  • Muscle weakness
  • Heart palpitations
  • Exophthalmos aka bulging eyes (not in every case) due to increased fatty deposits behind eyes
    increased T3 and T4 and very low TSH
    Low TSH explained in next slide
33
Q

What is grave’s disease

A
  • Autoimmune disease resulting in hyperthyroidism
  • Autoimmune means body attacks own thyroid tissue
  • Caused by production of thyroid stimulating immunoglobulin (TSI)
  • TSI continually stimulates thyroid hormone secretion outside normal negative feedback control
  • Low plasma TSH despite elevated T3 and T4
  • This is paradoxical, but as TSI is outside normal negative feedback loop, the stimulation of the thyroid gland isn’t due to TSH, its due to TSI
34
Q

What is thyroid scintigraphy

A
  • Technetium-99m is used for isotope scanning of the thyroid with a gamma camera
  • Biological half life of 1 day
  • Therefore radiation exposure is relatively low
  • Also used for bone scan, myocardial perfusion imaging and brain imaging
35
Q

Antithyroid drugs

A
  • These generally inhibit thyroid peroxidase
  • Used to treat overactive thyroid (hyperthyroidism) eg Grave’s disease
  • Blocks formation of thyroid hormone
  • Eg carbimazole which is a pro-drug and is converted to methimazole in body
  • Prevents thyroid peroxidase from coupling and iodinating tyrosine residues on thyroglobulin