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C. Year 3 MLA Reproductive and Endocrinology > Thyrotoxicosis > Flashcards

Thyrotoxicosis Flashcards

1
Q

The thyroid is located below which important structure in the trachea and either side of what cartilaginous area?

1 - pharynx
2 - tongue
3 - vocal cords
4 - larynx

A

4 - larynx

- cricoid cartilage

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2
Q

What is the main function of the thyroid gland?

1 - regulate insulin sensitivity
2 - regulate basal metabolic rate
3 - regulate Ca2+ levels
4 - regulate cortisol release

A

2 - regulate basal metabolic rate

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3
Q

What important chemical that must be consumed in the diet is required for thyroid hormone production?

1 - vitamin K
2 - B12
3 - iodine
4 - iron

A

3 - iodine
- recommended 150ug/day
- contained within seafood, dairy products, seaweed, iodized salt, prunes, potatoes, lima beans

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4
Q

The thyroid is not a uniform structure, rather it is composed of follicles. Each follicle is composed of which type of epithelial cells?

1 - cuboidal epithelial cells
2 - squamous epithelial cells
3 - columnar epithelial cells
4 - transitional epithelial cells

A

1 - cuboidal epithelial cells

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5
Q

The thyroid is not a uniform structure, rather it is composed of follicles. Each follicle is composed of cuboidal epithelial cells. What is the name of the area contained within the follicles that is surrounded by cuboidal epithelial cells?

1 - thyroglubulin
2 - colloid
3 - follicle
4 - calcitonin

A

2 - colloid

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6
Q

The thyroid contains C cells. What do these cells secrete?

1 - Ca2+
2 - parathyroid hormone
3 - thyroglobulin
4 - calcitonin

A

4 - calcitonin

- regulate plasma calcium levels

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7
Q

Label the cross section of the thyroid gland using the labels below:

follicle
RBCs
capillary
C cells
colloid
cuboidal epithelial cells

A

1 - follicle
2 - capillary
3 - C cell
4 - cuboidal epithelial cell
5 - RBCs
6 - colloid

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8
Q

In development the thyroid gland develops from the floor of what?

1 - pharynx
2 - tongue
3 - vocal cords
4 - larynx

A

1 - pharynx

- near the root of the tongue

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9
Q

Colloid is a substance that is contained within the follicles of the thyroid gland. What is the colloid substance composed of?

1 - Ca2+
2 - parathyroid hormone
3 - thyroglobulin
4 - calcitonin

A
  • thyroglobulin

- thyroglobulin is a large (660 kDa) tyrosine rich dimeric glycoprotein

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10
Q

Colloid is a substance that is contained within the follicles of the thyroid gland. The colloid substance is rich in thyroglobulin, a large (660 kDa) tyrosine rich dimeric glycoprotein. The thyroglobulin is produced by which 2 organelles of the follicular cuboidal epithelial cells?

1 - rough endoplasmic reticulum
2 - smooth endoplasmic reticulum
3 - golgi apperatus
4 - perioxome

A

1 - rough endoplasmic reticulum
3 - golgi apperatus

- golgi

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11
Q

Thyroglobulin, the precursor for thyroid hormones and contains between 10-20 thyroid molecules that can be used to form thyroxine (T4) and triiodothyronine (T3). Iodine is bound to tyrosine residues of the thyroglobulin. Iodine and tyrosine are then cleaved from the thyroglobulin forming T1 and T2. T1 and T2 can the be combined to create T4 and T3. The thyroid secretes thyroxine (T4) and triiodothyronine (T3). What % of T3 and T4 are secreted?

A
  • triiodothyronine (T3) =7%
  • thyroxine (T4) = 93%
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12
Q

Triiodothyronine (T3) and thyroxine (T4) referred to as T3 and T4, why are they referred to as T3 and T4?

1 - number of thyroglobulin molecules
2 - refers to activity on metabolism
3 - refers to number of tyrosine
4 - refers to number of iodine

A

4 - refers to number of iodine

  • T3 = 3 iodine molecules
  • T4 = 4 iodine molecules
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13
Q

Triiodothyronine (T3) and thyroxine (T4) are referred to as T3 and T4 because the T relates t tyrosine amino acid and the number relates to the number of iodine molecules bound to the tyrosine (T3 = 3 iodine molecules and T4 = 4 iodine molecules). Does T3 or T4 have a longer half life?

A
  • T4 has a longer half life

- T4 can be converted into T3 within cells

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14
Q

What are the 2 major extra-thyroidal organs that convert Thyroxine (T4) into triiodothyronine (T3)?

1 - heart
2 - skeletal muscle
3 - liver
4 - kidneys

A

3 - liver
4 - kidneys

2 - kidney

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15
Q

The 2 major extra-thyroidal organs that convert Thyroxine (T4) into triiodothyronine (T3) are the liver and the kidneys. What enzyme is response for converting T4 into T3?

1 - iodothyronine de-iodinases
2 - HMG-CoA synthase
3 - HMG-CoA reductase
4 - lipase

A

1 - iodothyronine de-iodinases

- can convert to active or inactive T3

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16
Q

The 2 major extra-thyroidal organs that convert Thyroxine (T4) into triiodothyronine (T3) are the liver and the kidneys. Iodothyronine de-iodinases can convert T4 into the active T3. There are 3 types of de-iodinases:

  • Type I and II = catalyses T4 to biological active T3
  • Type III = catalyses T4 into reverse (inactive) T3.

Where is type I Iodothyronine de-iodinases most commonly found?

1 - liver
2 - kidneys
3 - thyroid
4 - all of the above

A

4 - all of the above

- type 2 (D2) = muscle, brain, pituitary, skin and placenta

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17
Q

The 2 major extra-thyroidal organs that convert Thyroxine (T4) into triiodothyronine (T3) are the liver and the kidneys. Iodothyronine de-iodinases can convert T4 into the active T3. There are 3 types of de-iodinases:

  • Type I and II = catalyses T4 to biological active T3
  • Type III = catalyses T4 into reverse (inactive) T3.

Where is type II Iodothyronine de-iodinases most commonly found?

1 - pituitary
2 - muscle
3 - CNS
4 - thyroid
5 - placenta
6 - all of the above

A

6 - all of the above

- type 2 (D2) = muscle, brain, pituitary, skin and placenta

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18
Q

The 2 major extra-thyroidal organs that convert Thyroxine (T4) into triiodothyronine (T3) are the liver and the kidneys. Iodothyronine de-iodinases can convert T4 into the active T3. There are 3 types of de-iodinases:

  • Type I and II = catalyses T4 to biological active T3
  • Type III = catalyses T4 into reverse (inactive) T3.

Where is type III Iodothyronine de-iodinases most commonly found?

1 - CNS
2 - placenta
3 - all of the above

A

3 - all of the above

- type 2 (D2) = muscle, brain, pituitary, skin and placenta

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19
Q

Re-organise how is thyroglobulin created in the cuboidal epithelial cells and secreted into the colloid?

1 - thyroglobulin is synthesised in rough endoplasmic reticulum
2 - endocytosis secretes vacuoles into colloid where iodine is added to the tyrosine molecules of the thyroglobulin
3 - thyroglobulin and peroxidase packed into vacuoles
4 - amino acid (tyrosine) and iodide are taken up by thyroid gland from blood
5 - sugars added to thyroglobulin in golgi

A

4 - amino acid (tyrosine) and iodide are taken up by thyroid gland from blood
1 - thyroglobulin is synthesised in rough endoplasmic reticulum
5 - sugars added to thyroglobulin in golgi
3 - thyroglobulin and peroxidase packed into vacuoles
2 - endocytosis secretes vacuoles into colloid where iodine is added to the tyrosine molecules of the thyroglobulin

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20
Q

Reorganise how thyroglobulin is converted into thyroxine (T4) and triiodothyronine (T3) and secreted into the blood?

1 - colloid droplets of thyroglobulin merge with lysosomes
2 - T3 and T4 are then secreted into the blood
3 - thyroglobulin broken down and endocytosed into the the cuboidal epithelial cells
4 - lysosomes proteolytic enzymes breakdown thyroglobulin into T3 and T4

A

3 - thyroglobulin broken down and endocytosed into the the cuboidal epithelial cells
1 - colloid droplets of thyroglobulin merge with lysosomes
4 - lysosomes proteolytic enzymes breakdown thyroglobulin into T3 and T4
2 - T3 and T4 are then secreted into the blood

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21
Q

What transporter is present on the basolateral membrane (closest to the blood vessels) of the thyroid follicular cells that allows iodide to enter the thyroid follicular cells?

1 - Na+/iodide symtransporter
2 - Na+/K+ ATPase
3 - pendrin
4 - thyroid peroxidase

A

1 - Na+/iodide symtransporter
- iodide molecule crosses with 2 Na+ molecules
- N+ moves down concentration gradient
- iodide- moves against concentration gradient as lots of iodide already in the cell

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22
Q

What is present on the apical membrane (facing the colloid) thyroid follicular cells that is initially involved in transporting iodide into the colloid and the oxidation of iodide into something else?

1 - Na+/iodide symtransporter
2 - Na+/K+ ATPase
3 - pendrin
4 - thyroid peroxidase

A

3 - pendrin an anion (negative charge ion) exchanged
- exchanges iodide- for Cl-
- involved in oxidising iodide into iodine in the colloid

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23
Q

Pendrin is present on the apical membrane (facing the colloid) of the thyroid follicular cells and is initially involved in oxidation of iodide into iodine. What other enzyme is involved in the oxidation of iodide to iodine and the binding of iodine to thyroglobulin?

1 - iodothyropsine de-ionidase
2 - thyroid peroxidase
3 - peroxidase
4 - lipase

A

2 - thyroid peroxidase

facilitates the formation of T3 and T4 through combinations of monoiodotyrosine (MIT) and diiodotyrosine (DIT)

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24
Q

Which of the following can be created through the binding of tyrosine and iodine?

1 - monoiodotyrosine (MIT)
2 - diiodotyrosine (DIT)
3 - triiodothyronine (T3)
4 - thyroxine (T4)
5 - all of the above

A

5 - all of the above

25
Q

Na+/Iodide symtransporters are present on the basolateral membrane (closest to the blood vessels) of the thyroid follicular cells that allows iodide to enter the thyroid follicular cells. What other transporter is present on the basolateral membrane to facilitate iodide going against the concentration gradient?

1 - Na+/iodide symtransporter
2 - Na+/K+ ATPase
3 - pendrin
4 - thyroid peroxidase

A

2 - Na+/K+ ATPase pump
- Na+ moves out of the cell and into the blood
- Na+ gradient allows Na+/iodide symtransporter to then function

26
Q

In the Chernobyl disaster there were large amounts of radiation in the form of iodine-131, which is a highly radioactive form of iodine. Iodine consumed in our normal diets is iodine-127, but the body is unable to tell the difference between the 2. Iodine is essential for creating thyroid hormones and is absorbed mostly by the thyroid. Why were people following the Chernobyl disaster given strong doses of K+/iodine?

1 - breaks down iodine 131
2 - stops thyroid from functioning
3 - iodine-127 means thyroid cells are full of iodine, so no iodine-131 can be absorbed
4 - all of the above

A

3 - iodine-127 means thyroid cells are full of iodine, so no iodine-131 can be absorbed

  • reduces the risk of thyroid cancer
27
Q

What does the hypothalamus secrete into the hypothalamo- hypophyseal portal system that then goes on to stimulate the thyroid gland?

1 - thyrotropin releasing hormone (TRH)
2 - adrenocorticotropic hormone (ACTH)
3 - corticotropin-releasing hormone (CRH)
4 -thyroid stimulating hormone (TSH)

A

1 - thyrotropin releasing hormone (TRH)

- pituitary gland = Thyroid-stimulating hormone (TSH) also known as thyrotropin

28
Q

The hypothalamus secretes thyrotropin releasing hormone (TRH) into the hypothalamo-hypophyseal portal system that then goes on to stimulate the pituitary gland. What does the pituitary gland then secrete to stimulate the thyroid gland?

1 - thyrotropin releasing hormone (TRH)
2 - adrenocorticotropic hormone (ACTH)
3 - corticotropin-releasing hormone (CRH)
4 -thyroid stimulating hormone (TSH)

A

4 -thyroid stimulating hormone (TSH)

- pituitary gland = Thyroid-stimulating hormone (TSH) also known as thyrotropin

29
Q

There is a small network of blood vessels within the brain that connects the hypothalamus and the pituitary gland. What is this network of blood vessels called?

1 - hypothalamic-hypophyseal portal
2 - pampiniform plexus
3 - hepatic portal system
4 - uterine venous plexus

A

1 - hypothalamic-hypophyseal portal system

30
Q

Once the thyroid gland has been stimulated to secrete thyroxine (T4) and triiodothyronine (T3) and the levels in the blood rise, how do T3 and T4 then regulate further secretion of T3 and T4 from the thyroid gland?

1 - T4 inhibits thyroid gland directly
2 - T4 inhibits pituitary gland directly
3 - rT3 inhibits hypothalamus
4 - T4 inhibits hypothalamus

A

4 - T4 inhibits hypothalamus
- involved in negative feedback loop
- T3 in tissues inhibits hypothalamus and pituitary glands stimulation
- T4 in blood inhibits hypothalamus and pituitary glands stimulation

31
Q

Thyroid Stimulating Hormone (TSH) also known as thyrotropin is a glycoprotein produced by the thyrotrope cells of the anterior pituitary, which then goes on to stimulate the thyroid gland. What type of cell receptor does TSH bind with on the thyroid gland?

1 - tyrosine kinase receptors
2 - GPCR
3 - ion channels
4 - enzyme associated receptor

A

2 - GPCR

- specifically Gas

32
Q

Thyroxine (T4) and triiodothyronine (T3) are amino acid hormones, that behave like steroid hormones, so they are hydrophobic and need to be bound to plasma proteins to move around in the blood. 3 examples of liver synthesised plasma proteins that can transport T3 and T4 in the blood are:

  • thyroxine binding globulin (TBG)
  • thyroxine binding prealbumin or transthyretin (TTR)
  • albumin

How do T3 and T4 enter the cells?

1 - diffuse through cell membranes
2 - through active membrane transport called monocarboxylate transporter 8 (MCT8)
3 - Na+/T3 and T4 symptransporter
4 - ion channel

A

-2 - through active membrane transport called monocarboxylate transporter 8 (MCT8)

  • a transporter protein for thyroid hormones
33
Q

Once thyroxine (T4) binds and enters the cells through MCT8, what is typically the first thing that happens to it?

1 - converted into triiodothyronine (T3)
2 - binds with thyroid hormone receptors
3 - binds with retinoid X receptors (RXR)
4 - binds directly to DNA

A

1 - converted into triiodothyronine (T3)

- converted by de-iodinase

34
Q

Once thyroxine (T4) binds and enters the cells through MCT8, it is converted into triiodothyronine (T3) by de-iodinase. T3 then has a high affinity to bind with what?

1 - thyroxine (T4)
2 - binds with thyroid hormone receptors
3 - binds with retinoid X receptors (RXR)
4 - binds directly to DNA

A

2 - thyroid hormone receptors

35
Q

Once thyroxine (T4) binds and enters the cells through MCT8, it is converted into triiodothyronine (T3) by de-iodinase. T3 then has a high affinity to bind with thyroid hormone receptors. This then binds with what and enters the nucleus to act on DNA transcription?

1 - thyroxine (T4)
2 - binds with thyroid hormone receptors
3 - binds with retinoid X receptors (RXR)
4 - binds directly to DNA

A

3 - retinoid X receptors (RXR)

36
Q

Once thyroxine (T4) binds and enters the cells through MCT8, it is converted into triiodothyronine (T3) by de-iodinase. T3 then has a high affinity to bind with thyroid hormone receptors (THR). This then binds with retinoid X receptors (RXR) inside the nucleus. What is the THR/RXR receptor complex then able to do?

1 - inhibits thyroxine (T4)
2 - binds with thyroid hormone receptors
3 - binds with retinoid X receptors (RXR)
4 - binds directly to DNA

A

4 - binds directly to DNA

  • specifically the THR aspect of the THR/RXR complex binds to DNA
  • binds to part of DNA called thyroid hormone response elements or hormone response elements (HREs)
  • binding to the HREs is able to modulates gene expression, transcription and protein synthesis
37
Q

The figure below shows the basal metabolic rate following an injection of thyroxine (T4) and the following de-iodination by iodothyronine deiodinase enzyme creating triiodothyronine (T3). How does this explain the curve observe in the figure below in relation to basal metabolic rate (BMR)?

A
  • low BMR initially as the T4 has not undergone de-iodination by iodothyronine deiodinase enzyme
  • as T4 begins to undergo de-iodination the levels of T3 increase as does BMR
38
Q

What is the normal secretion levels of thyroxine (T4) and triiodothyronine (T3) by the thyroid gland?

A
  • T4 = 100ug

- T3 = 35ug

39
Q

What is Graves disease?

1 - autoimmune disease causing hypothyroidism
2 - autoimmune disease causing adrenal insufficiency
3 - autoimmune disease causing hyperthyroidism
4 - autoimmune condition where there is too much cortisol

A

3 - autoimmune disease causing hyperthyroidism

  • likely to be due to TSH receptor antibodies
  • accounts for 75% of autoimmune caused hyperthyroidism
40
Q

Which of the following are common symptoms of Graves disease (Hyperthyroidism)?

1 - unintentional weight loss (even if appetite and intake remains constant)
2 - tachycardia
3 - arrhythmia
4 - palpitations
5 - increased appetite
6 - nervousness, anxiety and irritability
7 - all of the above

A

7 - all of the above

41
Q

Which of the following are common clinical signs of Graves disease (Hyperthyroidism)?

1 - tremor
2 - warm and moist skin
3 - tachycardia
4 - brisk reflexes
5 - eye signs
6 - thyroid bruit
7 - muscle weakness
8 - atrial fibrillation
9 - all of the above

A

9 - all of the above

42
Q

If a patient presents with low levels of thyroid stimulating hormone (TSH) and high levels of thyroxine (T4) and triiodothyronine (T3), is this likely to be hyperthyroidism or hypothyroidism?

A
  • hyperthyroidism (primary
  • high levels of T3 and T4 cause negative feedback on pituitary gland reducing TSH
  • despite low TSH there is still elevated T3 and T4
43
Q

What are the 3 main things that can happen if a patient with graves disease, a form of hyperthyroidism is not treated promptly?

1 - systemic symptoms may escalate
2 - atrial fibrillation
3 - osteoporosis
4 - all of the above

A

4 - all of the above

44
Q

What is a thyrotoxic, most commonly observed in graves disease?

1 - low levels of thyroid hormones
2 - low mineral and glucocorticoids
3 - excessively high levels of thyroid hormones
4 - excessive levels of cortisol

A

3 - excessively high levels of thyroid hormones

  • significant magnification of symptoms associated with elevated thyroid hormones

1 - speed up the basal metabolic rate
2 - more proteins may be produced and more energy in the form of sugars and fats is burnt off, cells essentially going into hyperdrive
3 - T3 increases cardiac output
4 - stimulate bone resorption - thinning out the bones
5 - activates the sympathetic nervous system

45
Q

Thyrotoxicosis is significant and toxic thyroid hormones in the blood. Once T4 has been metabolised into T3, which of the following effects can excessive levels of T3 have in thyrotoxicosis have on a patient?

1 - speed up the basal metabolic rate
2 - increased catabolic state (proteins, glycogen and lipids are broken down for energy)
3 - increased cardiac output due to increased heart rate
4 - stimulation of osteoclasts (bone resorption)
5 - activation of the sympathetic nervous system
6 - all of the above

A

6 - all of the above

46
Q

Are patients with a confirmed diagnosis of Graves or undiagnosed with Graves disease more likely to suffer with thyrotoxicosis?

A
  • undiagnosed
47
Q

Thyrotoxicosis, most commonly observed in graves disease is when there is a significant magnification of symptoms associated with elevated thyroid hormones. Where T3 is able to do the following, but in a much more accentuated version than normal:

1 - speed up the basal metabolic rate
2 - more proteins may be produced and more energy in the form of sugars and fats is burnt off, cells essentially going into hyperdrive
3 - increases cardiac output (tachycardia, arrhythmias, heart failure
4 - stimulate bone resorption - thinning out the bones
5 - activates the sympathetic nervous system (GI issues)
6 - result in ICU and high mortality

This is common in patients with graves disease who are undiagnosed or patients with graves disease, but not compliant with treatment. Which of the following is a common trigger for Thyrotoxicosis?

1 - pregnancy
2 - surgery
3 - acute severe illness
4 - all of the above

A

4 - all of the above

  • essentially graves disease with some form or trigger
48
Q

What is the difference between thyrotoxicosis (toxic levels of thyroid hormones in the blood) and thyroid storm, also known as thyroid or thyrotoxic crisis (dangerous and significant increase in symptoms caused by hyperthyroidism)?

A
  • thyrotoxicosis - a common endocrine condition, generally secondary to a number of underlying processes
  • thyroid storm represents the severe end of the spectrum of thyrotoxicosis and is characterised by compromised organ function
49
Q

To diagnose thyrotoxicosis we can measure thyroid stimulating hormone. Would this typically be high or low in thyrotoxicosis?

A
  • low
  • BUT T4 and T3 remain high
50
Q

Is it important to measure thyroid stimulating hormone (TSH) in thyrotoxicosis?

A
  • yes
  • autoimmunity is most common cause of Graves (hyperthyroidism)
  • likely to be due to TSH receptor antibodies
  • causes a form of hyperthyroidism
51
Q

In addition to assessing levels of thyroid stimulating hormone (TSH) and TSH autoantibodies, which of the following may be raised in thyrotoxicosis?

1 - LFTs
2 - Ca2+
3 - normocytic anaemia
4 - Erythrocyte Sedimentation Rate (ESR)
5 - all of the above

A

5 - all of the above

52
Q

Which of the following medications is typically prescribed in thyrotoxicosis to address the AF, increased cardiac output and sympathetic tone?

1 - Ramipril
2 - Doxazosin
3 - Bisoprolol
4 - Verapamil

A

3 - Bisoprolol

  • B-blocker
53
Q

Which of the following medications is typically prescribed in thyrotoxicosis to act directly on the elevated thyroid hormones?

1 - Levothyroxine
2 - Propylthiouracil
3 - Teriparatide
4 - Cholecalciferol

A

2 - Propylthiouracil

  • inhibits Thyroid peroxidase (TPO)
  • TPO oxidizes iodide ions to form iodine atoms
  • iodine can then be added to thyroglobulin to form thyroxine (T4) or triiodothyronine (T3)
54
Q

Carbimazole, which inhibits Thyroid peroxidase (TPO) which is required for oxidising iodide ions to form iodine ions is often prescribed to patients in thyrotoxicosis. This has a number of adverse events, what is a rare but dangerous adverse event?

1 - liver failure
2 - renal failure
3 - agranulocytosis
4 - cardiac failure

A

3 - agranulocytosis

  • if signs of infection seek medical advice as this can lead to sepsis
55
Q

Patients with thyrotoxicosis can often be prescribed levothyroxine (synthetic T4) alongside Carbimazole (inhibits Thyroid peroxidase (TPO)). Why are these patients given more T4?

A
  • reduces risk of iatrogenic hypothyroidism
56
Q

Radioactive Iodine (I-131) Therapy can be used in thyrotoxicosis. How does this work?

1 - binds to T3 and inhibits their action
2 - blocks T4 from binding with tissues
3 - absorbed by thyroid gland and destroys thyroid cells
4 - inhibits Thyroid peroxidase (TPO)

A

3 - absorbed by thyroid gland and destroys thyroid cells

56
Q

Surgery can be used in thyrotoxicosis. Is this typically partial or total thyroidectomy?

A
  • total
  • risk of damage to recurrent laryngeal nerve
  • can result in hypothyroidism
57
Q

Is thyrotoxicosis and thyroid storm the same thing?

A
  • no
  • thyrotoxicosis is toxic levels of thyroid hormones
  • thyroid storm is the severe end of thyrotoxicosis which can lead to organ dysfunction

C. Year 3 MLA Reproductive and Endocrinology (22 decks)

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