Chemical pathology 8 - Thyroid

Question 1

What % of T4 is typically bound to TBG?

Answer 1

75%

Question 2

To which proteins can T4 bind?

Answer 2

TBG- thyroid binding globulin
TBPA- thyroxine binding prealbumin
Albumin

**TBG production depends on albumin itself**

• essenially very little of it is free

Question 3

Recall the possible aetiologies of primary hypothyroidism

Answer 3

Mnemonic: Hypothyroidism Possible Aetiology
Main causes are:
H = Hashimoto’s - this is the most common
P = Post-Grave’s disease - the treatment is radio-iodine which can cause hypothyroid
A = Atrophic
Other causes (more rare):
Drugs (eg lithium and amiodarone)
Thyroid dysgenesis
Peripheral T3 resistance

Question 4

What is the expected TSH and T4 levels in primary hypothyroidism?

Answer 4

TSH high
T4 low

Question 5

What test should always be done before thyroid-replacement medication is initiated?

Answer 5

ECG - because T4 increases cardiac contractility

Question 6

How does thyroid function change in pregnancy?

Answer 6

In 1st trimester, there is a huse rise in hCG
hCG has the same configuration as TSH - this then stimulates the thyroid gland to produce supra-physiological amounts of thyroxine
However, this is normal in pregnancy, so the woman doesn’t become clinically hyperthyroid

Question 7

What type of non-thyroid malignancy can cause thyrotoxicosis?

Answer 7

Malignancy that produces hCG

Question 8

What test is used to detect neonatal hypothyroidism?

Answer 8

Guthrie test on day 2/3 of life

Question 9

What does the term ‘sick euthyroid’ refer to?

Answer 9

Any severe illness –> reduced T4, increased TSH and decreased T3
This is normal physiology in sepsis

Question 10

Recall 5 differentials for the cause of hyperthyroidism, and how each would appear on a technetium scan

Answer 10

1. Grave’s (40-60% of cases) - high uptake
   2. Toxic multinodular goitre - high uptake
   3. Single toxic adenoma - high uptake
2. Subacute thyroiditis/viral (INITIAL PHASE where thyorid hormone is released from the gland) - low uptake
3. Postpartum thyroiditis (INITIAL PHASE where thyroid hormone is released from the gland) - low uptake

HIGH T4/T3

LOW TSH

__-

Other rarer differentials:

1) factitious- intake of thyroiine (high T4, normal TSH)
2) pituitary problem - TSHoma (high T4/T3 and High TSH)
3) thyorid cancer induced
4) trophoblastic tumour (hcg mimics TSH) or struma ovarii (high T4, normal TSH)

Question 11

Treatment of hyperthyoridism

Answer 11

in order

Question 12

What is the main risk of carbimazole and propylthiouracil treatment?

Answer 12

Agranulocytosis

Question 13

Over how long should carbimazole and propylthiouracil treatment be titrated ?

Answer 13

18 months

Question 14

How should papillary thyroid Ca be treated?

Answer 14

Removal of thyroid gland
Then radioiodine treatment
Then give supraphysiological thyroxine (so Ca cells not reactivated)

Question 15

Recall 2 tumour markers for medullary thyroid cancer

Answer 15

CEA and calcitonin

Question 16

Which type of thyroid cancer is associated with Men II?

Answer 16

Medullary

Question 17

WHat is the most common cause of hypothyoridism?

Answer 17

most causes are primary i.e. a problem with the thyroid gland itself rather than a problem with the pituitary

worldwide- iodine deficiency

uk - hashimotos (autoimmune)

Question 18

Clinical features of hypothyoridism

Answer 18

• Low metabolic rate- e.g. tiredness, lethargy
• Cardiovascular- e.g. bradycardic
• GI- e.g. constipation
• Respiratory- e.g. breathing is more laboured
• Reproductive- e.g. oligomenorrhoea, infertility
• Weight gain (reduced resting energy expenditure) and poor appetite
• Cold and dry hands, feels cold
• Hyponatraemia: rmb it causes euvolaemic hyponatraemia
• Normocytic anaemia:unless they have pernicious anaemia
• Lack of intrinsic factor → poor vitamin B12 absorption
• would be macrocytic anaemia- another autoimmune condition similar to thyroid disease
• Myxoedema madness
• goitre
• Subtle in elderly
• Secondary hypothyroidism → pituitary tumour leads to the development of visual problems

Question 19

What does high TSH and normal T4 indicate?

Answer 19

Either treated hypothyroidism or subclinical hypothyoridism

subclinical hypothyoridism- measure anti-TPO antibodies; if positvie then they have a chance of developing hypothyoridism later on in life.

only benefit of treating subclinical hypothyroidism is if they have hypercholesteramiea

Question 20

What do you see in sick euthyroid disease and what is it?

Answer 20

In any severe illness, the thyroid gland shuts down to preserve metabolic rate

Low T3/T4–> high TSH (later comes back to normal)

Question 21

Clinical features of hyperthyoridism

Answer 21

Raised metabolic rate (weight loss)

Cardiovascular (tachycardia, AF, palpitations)

GI (e.g. diarrhoea)

Respiratory (e.g. tachypnoea)

Skeletal (e.g. osteopaenia/ osteoporosis)

Reproductive (e.g. irregular periods, infertility)

Question 23

Features of graves disease

Answer 23

• Diffuse smooth goitre
• Exophthalmos
• Thyroid associated dermopathy (pretibial myxoedema)
• Thyroid acropachy (bones and fingers)
• Other autoimmune disease (or family history)

anti TSH receptor antibody positive

Question 24

Summary of the main causes of hypo and hyperthyoridism and how to distinguish between them

Answer 24

Question 25

Antiboduyes in ahshimotors

Answer 25

anti TPO or anti thyroglobulin

Question 26

Papillary thyroid cancer - tumour marker

Answer 26

thyroglobulin

Question 27

Follicular thyorid cancer- tumour marker

Answer 27

thyroglobulin

Question 28

3 multiple endocrine neoplasias

Answer 28

MEN1 (3Ps): Pituitary, Pancreatic (e.g. insulinoma), Parathyroid (hyperparathyroidism)

MEN2a (2Ps, 1M): Parathyroid, Phaeochromocytoma, Medullary thyroid

MEN2b (1P, 2Ms): Phaeochromocytoma, Medullary thyroid, Mucocutaneous neuromas (& Marfanoid)

Question 29

Thyroid neoplasias

Answer 29