Thyroid gland

Question 1

What is the epidemiology of thyroid disorders?

Answer 1

Affect 5% of women and 0.5% of men in the population

Question 2

Describe the thyroid gland

Answer 2

Two highly vascular lobes either side of trachea, weighing 10-20g

Contains follicles made up of single layer of cells surrounding a lumen containing colloid (largely
thyroglobulin)

Question 3

What is a significant complication of a thyroidectomy?

Answer 3

bleeding following surgery can lead to compression of the trachea and
respiratory interruption.

Question 4

Describe the follicular cells

Answer 4

When stimulated, these cells become columnar and the
lumen is depleted of colloid

When suppressed, the cells become flat and colloid
accumulates in the lumen

Question 5

What is the role of iodine in the thyroid?

Answer 5

thyroid gland has evolved to take up and store iodine, the essential component of thyroid hormones
=> necessary for thyroid hormone synthesis

Question 6

How is iodine used in thyroid hormone synthesis?

Answer 6

• oral iodine is reduced to iodide in the GI tract and absorbed
• Iodide is transported into follicular cells against a chemical gradient on the basolateral membrane by the
  sodium iodide transporter (active transport)
  o Allows follicular cells to concentrate iodide

Iodide then diffuses to apex of cell and is transported by prendrin into vesicles fused with the apical cell
membrane

Oxidation of iodide to iodine occurs in the vesicles and binds to tyrosine residues on thyroglobulin
o This process is called organification – catalysed by thyroid peroxidase

Question 7

How are thyroid hormones synthesised?

Answer 7

Formation of DIT/MIT, then T3/T4 and endocytosis of thyroglobulin into cell

• droplets fuse with lysosome and thyroglobulin is hydrolysed => release of T3, T4 into circulation

Question 8

What happens to thyroid hormone synthesis in iodine deficiency?

Answer 8

the body makes predominantly T3 (uses less iodine and is more active)

Question 9

What is thyroglobulin?

Answer 9

Polypeptide backbone for the synthesis and storage of thyroid hormones

Question 10

What is the preliminary step of MIT and DIT formation?

Answer 10

Iodine attachment to tyrosyl residues on thyroglobulin

(Iodine combines with tyrosine to form mono or di-iodinated thyronine
These combine to form T3 and T4)

Question 11

How are T3 and T4 released?

Answer 11

Proteolytic cleavage in lysosomes

Question 12

Describe release of T4

Answer 12

released in greatest quantity, and solely, by the thyroid gland

Question 13

Describe T3

Answer 13

T3 is the more active hormone, formed by peripheral 5’ deiodination of T4

Question 14

Describe the circulating thyroid hormones

Answer 14

Free (0.5%) / bound (99.5%)
o Free component is the active and regulated component
o Bound to thyroid binding globulin, transthyretin and albumin

Question 15

What happens to T4?

Answer 15

converted to T3 in the periphery. T3 then binds to its nuclear receptor

Question 16

How are thyroid hormones regulated?

Answer 16

TSH from anterior pituitary stimulates synthesis and secretion of T4 and T3

TSH secretion is inhibited by T4 and T3 (negative feedback)

TRH from HPS stimulates TSH secretion

Question 17

How is thyroid hormone action mediated?

Answer 17

by nuclear receptors

Question 18

How is the majority of T3 generated?

Answer 18

locally from T4

varies between tissues

Question 19

What is the action of T3?

Answer 19

Cytosolic T3 is transported into nuclei and binds to receptor

• Alpha and beta T3 nuclear receptors vary between tissues
• Binding increases protein synthesis, and proteins mediate the observed effects

Question 20

How does thyroid hormone effect foetal development?

Answer 20

Foetus requires maternal thyroid hormones for brain

development

Question 21

What is the influence of thyroid hormones?

Answer 21

Influence on nearly every system (more T3 nuclear receptors in more
sensitive tissues, such as pituitary and liver)
o Skeletal - Bone turnover
o Cardiovascular - Heart rate
o Metabolic – lipids and glucose

Question 22

Briefly describe primary hypothyroidism

Answer 22

High TSH and low T4
o Disease is in the thyroid gland
o Treat with thyroxine

Question 23

Briefly describe secondary hypothyroidism

Answer 23

Low TSH and low T4
o Pituitary cause of disease
o May also have other pituitary axis hormone deficits
o Make sure their cortisol is okay before commencing thyroxine
treatment

Question 24

Briefly describe primary hyperthyroidism

Answer 24

Low TSH and high T4

Question 25

Briefly describe sick euthyrodism

Answer 25

low TSH and low T4 o Effect on thyroid hormones with other illness (e.g. malignancy), but not fundamental thyroid disease

Question 26

What are the causes of hyperthyroidism?

Answer 26

Excess thyroid hormone - auto-immune (Graves' disease) - toxin adenoma - multinodular goitre - thyroiditis - excess thyroxine

Question 27

What are the clinical manifestations of thryotoxicosis?

Answer 27

``` o Weight loss o Tachycardia o Tremor o Hypertension (high pulse pressure - high systolic and low diastolic BP) o Heat intolerance o Palpitations o Diarrhoea o Sweating ```

Question 28

What is toxic adenoma?

Answer 28

solitary nodule over secreting thyroid hormones

Question 29

What is multinodular goitre?

Answer 29

can be either a toxic multinodular goiter (causes hyperthyroidism) or non- toxic (does not make too much thyroid hormone).

Question 30

What is thyroiditis?

Answer 30

generally caused by an attack on the thyroid, resulting in inflammation and damage to the thyroid cells

Question 31

What symptoms are specific to Graves' disease?

Answer 31

Dysthyroid eye disease o Dermopathy – In 1-2% patients  red, swollen skin, usually on the shins and tops of the feet.  The texture of the affected skin may be similar to that of an orange peel

Question 32

What is Graves' opthalmopathy?

Answer 32

autoimmune inflammatory disorder of the orbit and periorbital tissues ``` characterized by: o Lid retraction / lag and periorbital oedema o Proptosis (30%) = Exophthalmos o Diplopia (10%) = double vision ```

Question 33

What is the pathophysiology of Graves' ophthalmopathy?

Answer 33

-Autoantibodies target the fibroblasts in the eye muscles, which can differentiate into adipocytes. -Fat cells and muscles expand and become inflamed. -inflammation results in a deposition of collagen and glycosaminoglycans in the muscles, which leads to subsequent enlargement and fibrosis -This increases in volume of the intraorbital contents within the confines of the bony orbit  -Veins become compressed, and are unable to drain fluid, causing oedema

Question 34

What is Thyroid acropachy

Answer 34

soft tissue swelling of the hands and clubbing of the fingers

Question 35

How is Graves' managed?

Answer 35

Antithyroid drugs Surgery – will lead to hypothyroidism Radio iodine - will probably lead to hypothyroidism

Question 36

Which anti-thyroid drugs are used in the treatment of hyperthyroidism?

Answer 36

Thionamides | carbimazole, propylthyouracil

Question 37

Describe radioiodine therapy for Graves' disease

Answer 37

 Destroys thyroid tissue by beta emission  May worsen eye disease – ensure steroid cover and avoid hypothyroidism  Defer conception for at least 4 months  Hypothyroidism is main side effect o May be transient in first 6 months  50% patients given high dose at one year

Question 38

What are the complications of thyroid surgery?

Answer 38

o Haemorrhage 0-1.3% o Rec laryngeal palsy 0-4.5% o Permanent hypocalcaemia 0.6% o Hypothyroidism

Question 39

What are the causes of hypothyroidism?

Answer 39

- auto-immune - thyroiditis - thyroidectomy - radioiodine therapy - drug induced - pituitary disease - severe iodine deficiency

Question 40

What is Hashimotos?

Answer 40

Autoimmune thyroid disease o Destruction of the thyroid gland (anti TPO antibody) o May be positive family history, more common in females

Question 41

What drugs can induce hypothyroidism?

Answer 41

o Amiodarone (antiarrhythmic drug, contains a lot of iodine) o Lithium o Sunitinib

Question 42

What are the symptoms of hypothyroidism?

Answer 42

```  Weight gain  Depression  Lethargy  Constipation  Cold intolerance  Poor concentration  Hoarseness  Menorrhagia - menstrual periods with abnormally heavy or prolonged bleeding ```

Question 43

What are the signs of hypothyroidism?

Answer 43

```  Weight gain  Bradycardia  Lethargy  Dry skin  Coarse, thin hair  Anaemia  Slow relaxing reflexes  May have goitre ```

Question 44

What is goitre?

Answer 44

 Swelling in the neck resulting from an enlarged thyroid gland.   Not only seen in hypothyroidism  May be hyperthyroid or euthyroid with nodular disease

Question 45

What investigations are done in hypothyroidism?

Answer 45

Measure: o Free T4 o TSH - Primary hypothyroidism = High TSH and low T4 - Secondary hypothyroidism = Low TSH and low T4

Question 46

What is the main treatment for hypothyroidism?

Answer 46

levothyroxine

Question 47

What is the typical dosage regimine of levothyroxine?

Answer 47

o Generally need 1.7-2.0 micrograms / kg / day (with no gland whatsoever) o Best taken on an empty stomach o Avoid taking with proton pump inhibitors, ferrous sulphate or calcium  Start lower, especially in elderly and in cardiac disease o Increased thyroxine increases the load on the heart

Question 48

What are the treatment goals of hypothyroidism?

Answer 48

o Goal is to render patient euthyroid – Resolve symptoms and normalise TSH o Normal TSH is controversial  Range is 0.5 -5mU/L  Some suggest that a TSH around 2mU/L more appropriate  Full suppression of TSH is associated with Atrial fibrillation and osteoporosis

Question 49

What are the different types of thyroid cancer?

Answer 49

```  Differentiated (good prognosis) o Papillary 17% o Follicular 13-20% o Mixed 50% o Medullary Carcinoma of Thyroid 6%  Undifferentiated 15% (poorer prognosis) o Anaplastic o Small cell  Misc – Lymphoma, Sarcoma, Metastatic ```