Thyroid

Question 1

How does iodine get from the gut into thyroid cells?

Answer 1

Iodine enters the GI tract and is converted
into iodide

TSH controls uptake of iodide to the thyroid
(blocked by perchlorate)

Iodide goes through the basement membrane
via Na+/K+ ATPase

Question 2

How is thyroxine made?

Answer 2

The iodine is then taken up
by thyroglobulin and then converted into
thyroxine through a number of processes

The iodination of tyrosine residues
in thyroglobulin leads to the
formation of monoiodotyrosine and diiodotyrosine

Question 3

How is thyroxine used?

Answer 3

Once the thyroxine (T4) is produced, it is stored within the thyroid gland

When it needs to be released, it travels through the basement membrane and is secreted into
the capillary lumen

In the periphery, T4 will be converted to T3

Question 4

Which thyroid hormones can be measured?

Answer 4

T3 and T4 can be measured in the blood circulation

o You can also measure TSH, thyroglobulin and thyroid peroxidase
o Note: TRH is rarely measured

Question 5

How is thyroid hormone transported?

Answer 5

A very small proportion is active (free)
thyroxine (fT4)
o Only 0.03% of thyroxine in the
circulation is active

Most of it is bound to thyroxine binding
globulin (TBG)
o NOTE: if you are lacking
albumin, your TBG levels will
go down

Thyroxine can also bind to thyroxinebinding pre-albumin (TBPA) and albumin

Question 6

Draw out the HPT axis

Answer 6

Question 7

What is primary and secondary hypothyroidism?

Answer 7

Most hypothyroidism is PRIMARY hypothyroidism (i.e. pathology with the thyroid gland itself)

Secondary hypothyroidism – pathology in pituitary gland (5%)

Question 8

What is hashimotos thyroiditis?

Answer 8

Autoimmune disease

Goitre due to lymphocytic and plasma cell infiltration

Anti-thyroid antibodies including anti-thyroid peroxidase, anti-thyroglobulin and TSH-receptor blocking antibodies

Question 9

What is atrophic thyroiditis?

Answer 9

Autoimmune disease

Tends to affect women aged 40-60 years

Pathology: atrophic thyroid gland with lymphocytic infiltration and fibrous tissue replacing normal thyroid parenchyma

No goitre

Anti-TSH receptor antibodies blocking action of tsh

Question 10

What is Post-Graves’ disease (radioactive iodine, surgery, natural history or thionamines)?

Answer 10

Post-thyroiditis o Drugs (amiodarone, lithium)

Thyroid agenesis or dysgenesis o Iodine deficiency (severe iodine deficiency is commonest cause worldwide) and dyshormonogenesis

Secondary hypothyroidism, pituitary disease (TSH no utility)

Peripheral thyroid hormone resistance – receptors in tissues do not respond to thyroxine

Iodine excess (Wolff-Chaikoff effect)

Question 11

What are the clinical features of hypothyroidisn?

Answer 11

o Metabolic rate
o Cardiovascular (e.g. bradycardia)
o GI (e.g. constipation)
o Respiratory (e.g. laboured breathing)
o Reproductive (e.g. oligomenorrhoea)
o Others (e.g. pituitary symptoms such as visual symptoms due to optic chiasm being
affected)
o Weight gain with decreased resting energy expenditure and poor appetite
o Cold and dry hands, feels cold
o Hyponatraemia – thyroxine is involved with sodium transport in kidneys
o Normocytic anaemia due to bone marrow depression, unless pernicious
anaemia (another autoimmune condition which will cause macrocytic anaemia)
o Myxoedema: swelling of face and legs, and dry waxiness of skin
o Goitre
o Subtle in elderly
o Proximal myopathy

Question 12

What investigations would be positive in hypothyroidism?

Answer 12

o High TSH + low T4 in primary hypothyroidism
o Thyroid peroxidase autoantibodies (if present, suggests autoimmune
hypothyroidism)
o Think of other autoimmune conditions that the patient may also have (e.g. pernicious
anaemia, coeliac disease, Addison’s disease)

Question 13

What is the management of hypothyroidism?

Answer 13

ECG

Levothyroxine 50-125-200 µg/day titrated to a normal TSH

Note: rule out underlying adrenal insufficiency before starting thyroid hormone replacement as it can precipitate and Addisonian crisis

Question 14

Why should you do an ECG in someone with hypothyroidism?

Answer 14

If someone with hypothyroidism has underlying cardiovascular disease and
you give them thyroxine, their myocardial contractility will increase and they
may be at risk of ischaemia

So, you would want to start on a very low dose of thyroxine and build up if
the patient has cardiovascular disease

Question 15

What is myxoedema coma?

Answer 15

o Severe hypothyroidism leading to decreased mental status, hypothermia and reduced
function of multiple organs
o Medical emergency

Question 16

What is the treatment of myxoedema coma?

Answer 16

 Oxygen
 Rewarming
 Rehydration
 IV T4/T3: liothyronine (IV T3) has faster onset of action
 IV hydrocortisone
 Treat underlying cause e.g. infection

Question 17

Why does subclinical hypothyroidism exist?

Answer 17

 The T4 level is NORMAL but TSH is HIGH
 However, the pituitary gland senses that level of T4 and thinks that the thyroid hormone
is NOT producing enough thyroxine so it produces more TSH
 Sometimes referred to as compensated hypothyroidism
 These patients may not have clinical signs as T4 is normal
 If TPO antibodies are positive, it suggests that the patient may go on to develop thyroid
disease
 Subclinical hypothyroidism is UNLIKELY to be the cause of their presenting symptoms
 Hypothyroidism is associated with hypercholesterolaemia, so this may be the only benefit of
treating subclinical hypothyroidism

Question 18

What is hypothyroidism after radio iodine treatment?

Answer 18

 RAI is treatment for hyperthyroidism
 Most patients with this condition will become hypothyroid within 1 year of receiving
radioiodine treatment
 However, it may take many years in some patients (up to 15) – so ask about PMH of
hyperthyroidism

Question 19

Why does thyroid change happen in pregnancy?

Answer 19

 Thyroid hormone levels
change during pregnancy
 hCG has a similar structure
to TSH - so if you have too
much hCG, it can make the
thyroid gland produce too
much thyroxine (as it will
bind to same receptors as
TSH)
o Note: a malignancy
producing hCG will
cause rise in
thyroxine

Question 20

How does thyroid change during pregnancy?

Answer 20

 The rise in hCG in the first trimester of pregnancy makes your free T4 levels increase slightly

 This is a normal physiological process, so the ‘normal ranges’ of TSH and T4 in pregnancy are slightly different

 TBG levels increase dramatically in pregnancy because it is under the control of oestrogen
o But TBG cannot be measured in serum

 Later on in pregnancy, hCG levels will drop and, consequently, T4 levels will also go down
and the TSH levels will rise slightly (back to normal population levels)

Question 21

How is neonatal hypothyroidism found?

Answer 21

 Incidence: 1:3500
 This is diagnosed in the Guthrie test
 It is important to capture hypothyroidism at the correct time - if you measure it too early, their
TSH level may be erroneously high because of the presence of maternal TSH in the blood. If
done too late, it can cause problems in baby
 The Guthrie test is usually done at 48-72 hours and the TSH detected is coming from the baby
not the mother

Question 22

What is sick euthyroid?

Answer 22

Alteration in pituitary thyroid axis in non-thyroidal systemic illness
 Biochemistry
o Low T4 and T3
o Normal/high TSH

(May have normal T4 and high rT3)

 This can happen in any severe illness e.g. sepsis
 If you are very sick, your thyroid will shut down to try and reduce the basal metabolic rate
 These patients do NOT have hypothyroid symptoms and giving thyroxine will NOT improve their symptoms
 Hence always do TFTs in context of patient symptoms and signs

Question 23

What are the causes of hyperthyroidism?

Answer 23

Graves’ disease

Toxic multinodular goitre

Single toxic adenoma

Other causes: subacute thyroiditis, post partum thyroiditis, silent thyroiditis, factitious thyroiditis, TSH induced, thyroid cancer, trophoblastic tumour and struma ovarii

Question 24

What differentiates Graves’ disease, toxic multinodular goitre and single toxic adenoma?

Answer 24

o Graves’ disease (40-60%)
 TSH-receptor stimulating auto-antibodies
 Cause smooth thyroid enlargement
o Toxic multinodular goitre (30-50%)
 Aka Plummer’s disease
 Multiple autonomously functioning nodules (function independently of TSH)
o Single toxic adenoma (5%)
 An autonomously functioning thyroid nodule
 NOTE: a technetium scan can be used to see which parts of the thyroid are
producing excessive thyroid hormone. All three of the above conditions will
show increased uptake of technetium

Question 25

Why does thyroid have anything to do with pregnancy?

Answer 25

Post-partum thyroiditis
 In pregnancy, the body may produce antibodies that stimulate the
thyroid gland to release excess amounts of thyroxine
 These two have LOW uptake in a technetium scan

Trophoblastic tumour and Struma ovarii
 Due to excessive hCG production
 Struma ovarii: rare form of ovarian tumour (usually a teratoma) that
contains mostly thyroid tissue and produces thyroxine

Question 26

What are the clinical features of hyperthyroidism?

Answer 26

o Increased metabolic rate
o Cardiovascular (tachycardia)
o GI (e.g. diarrhoea)
o Respiratory (e.g. tachypnoea)
o Skeletal – thyroxine has direct effect on osteoclasts (e.g. osteopaenia/osteoporosis)
o Reproductive (e.g. irregular periods)

Question 27

What would you find on investigation of hyperthyroidism?

Answer 27

o Low TSH
o High T4 and T3
o Technetium scan may show high or low uptake
o Thyroid autoantibodies (thyroid microsomal (aka thyroid peroxidase antibody))

Question 28

What is the management of hyperthyroidism?

Answer 28

o Beta-blocker if pulse > 100 bpm
o Other autoimmune conditions (e.g. coeliac disease, Addison’s disease)
o ECG
o Bone mineral density
o Radioactive iodine

Question 29

What warnings should you give for radio iodine?

Answer 29

 The radioactive iodine is taken up by the thyroid gland, which then releases
radiation to destroy the thyroid gland
 DANGER: it can precipitate a thyroid storm -> can become cardiovascularly
decompensated
 It can make the thyroid gland underactive (i.e. hypothyroidism)
 Stop thionamine if using radioactive iodine
 Side effects: ophthalmopathy/tracheal compression

Question 30

What may Graves’ disease present with?

Answer 30

o Diffuse goitre
o Thyroid-associated ophthalmopathy (due to TSH receptors on eye muscles)
 IMPORTANT: radioiodine treatment can make Graves’ eye disease worse
o Thyroid-associated dermopathy (pretibial myxoedema)
o Thyroid acropachy (soft tissue swelling of the hands and clubbing of fingers)
o Other autoimmune conditions

Question 31

What is the pharmacology of thionamides?

Answer 31

o Examples: carbimazole, propylthiouracil
o They work by preventing the conversion of iodide to iodine by thyroid peroxidase
o There are several possible side-effects including rash
o IMPORTANT: a rare side-effect of thionamides is agranulocytosis (<1%)
 Patients should be advised to STOP the treatment if they develop a sore
throat or fever and they should immediately seek medical attention to do an
FBC
o These medications are either titrated to achieve normal T4 levels or they can be block
and replaced (a high dose of thionamides are used to block the thyroid gland
completely, then they are given thyroxine to maintain normal T4 levels)

Question 32

What does potassium perchlorate and thionamides do?

Answer 32

o Potassium perchlorate can be given to hyperthyroid patients before surgery to block
the uptake of iodide by the thyroid cells
o Thionamides inhibit thyroid peroxidase, thereby preventing the conversion of iodide
to iodine

Question 33

What is thyroiditis?

Answer 33

o Inflammation of thyroid gland
o De Quervain’s (viral) thyroiditis involves painful dysphagia and pyrexia
o You may get the condition without being symptomatic
o Most of the patients will have some form of pain in the neck
o With thyroiditis, you initially get inflammation of the thyroid gland resulting in excessive release of thyroid hormone
o Then, eventually, the thyroid hormone will stop working completely
 Whereas in Graves you get continuous thyroid production
o The long-term treatment of thyroiditis is thyroid hormone replacement
o Thyroiditis patients are likely to present at the stage where their TSH is high and their T4/T3 is low
o REMEMBER: the treatment for viral or post-partum thyroiditis is different to hyperthyroidism

Question 34

What is thyroid cancer?

Answer 34

 Types (MOST COMMON):
o Papillary thyroid cancer
o Follicular thyroid cancer
 This is typically a slow-progressing cancer

Question 35

What is the treatment of thyroid cancer?

Answer 35

Treatment: usually a total thyroidectomy

o Radioiodine treatment may be given after surgery to remove any remaining thyroid cells
o After this, patients are given high doses (suprafollicular doses) of thyroxine (this
lowers the TSH levels so that TSH does NOT stimulate any remaining thyroid cancer cells)

Question 36

What is the use of thyroglobulin?

Answer 36

 Thyroglobulin in the serum can be measured as a tumour marker to see whether the thyroid cancer has come back
o TG indicates functioning thyroid tissue
o This can be measured when TSH is suppressed or when TSH is stimulated

Question 37

What is a medullary carcinoma of the thyroid gland?

Answer 37

o This is RARE but can be devastating
o It can be sporadic, familial or part of MEN 2
o It is a cancer of the C cells of the thyroid gland (these produce calcitonin)
o Tumour markers:
 Calcitonin
 CEA (carcinoembryonic antigen)

Question 38

Pick the correct answer

Answer 38

6

Question 39

Answer 39

1

Question 40

Answer 40

2

Question 41

Answer 41

1

Question 42

Answer 42

5