ChemPath: Thyroid

Question 1

What controls the uptake of iodide by thyroid follicular cells?

Answer 1

TSH

Question 2

Which channel is important for the transport of iodine across the cell membrane?

Answer 2

Na+/K+ ATPase

Question 3

Which enzyme converts iodide to iodine?

Answer 3

Thyroid peroxidase - happens in thyroid follicular cells

happens in thyroid gland

Question 4

How is thyroxine produced?

Answer 4

Iodination of tyrosine residues in thyroglobulin generates MIT and DIT which leads to the formation T3 and T4

happens in the colloid

Question 5

what percentage of thyroxine is free active T4?

Answer 5

0.03%

Question 6

What does thyroxine bind to in the blood?

Answer 6

• 75% - Thyroxine binding globulin (TBG)
• 20% - Thyroxine-binding prealbumin (TBPA)
• 5% - Albumin

Question 7

Outline the hypothalamo-pituitary-thyroid axis.

Answer 7

• The hypothalamus produces TRH which stimulates the release of TSH from the anterior pituitary
• TSH stimulates T3/T4 production
• T3 is active hormone and produced in perpipheries
• T4 -ve feedback to the hypothalamus and pituitary

Question 8

List some causes of hypothyroidism.

Answer 8

• Hashimoto’s thyroiditis (autoimmune)
• Atrophic thyroid gland
• Iatrogenic - Post-Graves’ disease (after treatment e.g. radioiodine, thionamides, surgery)
• Post-thyroiditis
• Drugs (e.g. amiodarone, lithium)
• Iodine deficiency
• Pituitary disease - secondary
• Peripheral thyroid hormone resistance

Question 9

Outline the investigation findings that may be seen in hypothyroidism.

Answer 9

• High TSH
• Low T4
• Thyroid peroxidase antibodies
• Other autoimmune conditions - coeliac, pernicious anaemia, addison’s
• ECG

Question 10

Why is it important to do an ECG in patients with suspected hypothryoidism?

Answer 10

If someone with hypothyroidism has underlying cardiovascular disease, giving them thyroxine may induce ischaemia

NOTE: so you would start on a low dose of thyroxine and then escalate if they have CV

Question 11

Symptoms of hypothyroidism

Answer 11

Metabolic - gain weight
GI - constipation
Reproductive - amenorrhea

Depression
Cold intolerance
Fatigue

Question 12

How is hypothyroidism treated?

Answer 12

Thyroxine (50-150-200 µg/day titrated to a normal TSH)

NOTE: you replace with T4, giving T3 has no clinical benefit

dose is adjusted to weight

Question 13

What are some risks of overtreatment with thyroxine?

Answer 13

• Osteopaenia
• Atrial fibrillation

Question 14

What is a subclinical hypothyroidism?

Answer 14

• Normal T4 with high TSH
• Sometimes referred to as compensated hypothyroidism

NOTE: if TPO antibodies are positive, the patient may go on to develop hypothyroidism

Question 15

Why might there be some benefit to treating subclinical hypothyroidism?

Answer 15

• Hypothyroidism is associated with hypercholesterolaemia

Question 16

Outline how thyroid function changes in pregnancy.

Answer 16

• hCG has a similar structure to TSH so high hCG levels can cause hyperthyroidism in 1st trimester
• Free T4 levels rise slightly
• TSH levels decrease slightly
• Clinically they are not hyperthyroid - it is normal, different reference ranges
• TBG level increase dramatically due to estrogen increase (but this cant be measured in serum)

NOTE: hCG level drops later on in pregnancy

Question 17

How is neonatal hypothyroidism diagnosed?

Answer 17

Guthrie test - measures TSH

Question 18

Why is the timing of the Guthrie test important?

Answer 18

It needs to be done at least 48-72 hours after birth to make sure maternal TSH is no longer in the baby

Later would cause brain damage due to congenital hypothyroidism

Question 19

What is sick euthyroid?

Answer 19

• Alteration in the pituitary thyroid axis in non-thyroidal illness
• In other words, when you are very sick, your thyroid will shut down to try and reduce your basal metabolic rate

Question 20

What are the TFT findings in sick euthyroid?

Answer 20

• Low T4 and T3
• Normal/high TSH

NOTE: these patients do not have symptoms of hypothyroidism

normal physiology

Question 21

What are the three main causes of hyperthyroidism?

Answer 21

• Graves’ disease - anti-TSH antibodies
• Toxic multinodular goitre
• Single toxic adenoma

Others: subacute/viral thyroiditis, post-partum thyroiditis

Question 22

Explain varying results of technetium uptake scan for causes of hyperthyroidism

Answer 22

increased uptake:
graves, toxic multinodular goitre, single toxic adenoma - thyroxtoxicosis is due to increased production of thyroxine

decreased uptake
subacute/viral thyroididts, post-partum thyroiditis - thyrotoxicosis is due to release of PRE-FORMED thyroxine, not increased production, eventually become hypothyroid

Question 23

key distinguishing symptom of viral thyroiditis

Answer 23

painful goitre

Question 24

What is post-partum thyroiditis?

Answer 24

During pregnancy, the body may produce antibodies that stimulat the thyroid gland

Question 25

What is struma ovarii?

Answer 25

A rare form of ovarian tumour (usually a teratoma) that contains mostly thyroid tissue and produces thyroxine

Question 26

List some investigation findings of hyperthyroidism.

Answer 26

* Low TSH * High T4 and T3 * Technetium scan * Thyroid antibodies (thyroid microsomal)

Question 27

Clinuical signs of hyperthyroid

Answer 27

metabolic - weight loss, increased appetitie cardiac - tachycardia, palpitations GI - diarrhoea respiratory - tahcypnoea skeletal - osteopenia/osteoporosis reproductive - irregular periods, infertility heat intolerance, anxiety

Question 28

Outline the management of hyperthyroidism.

Answer 28

* symptomatic - Beta-blocker * ECG - check for AF * Bone mineral density - to look for ostepenia/osteoporosis * Radioiodine * Thionamides

Question 29

What is a major risk of radioiodine treatment for hyperthyroidism?

Answer 29

* Can precipitate thyroid storm * results in hypothyroidism --> give thyroxine Also not if they have graves eye disease

Question 30

List some features of Graves' disease.

Answer 30

* Diffuse goitre * Thyroid-associated ophthalmopathy * Pretibial myxoedema * Thyroid acropachy NOTE: radioiodine can make Graves' eye disease worse

Question 31

What is the mechanism of action of thionamides?

Answer 31

Inhibit thyroid peroxidase - Prevents the conversion of I- to I2 and iodination of tyrosine residues on thyroglobulin | Carbimazole, PTU

Question 32

What is a rare but important side-effect of thionamides?

Answer 32

Agranulocytosis NOTE: patients should be advised to stop treatment if they develop a sore throat or fever

Question 33

What kind of dosing regimes can be used for thionamides?

Answer 33

* Can be titrated to achieve normal T4 or * Block and replace - high dose is given to block the thyroid gland and then given thyroxine replacement

Question 34

Which drug can be given to hyperthyroid patients prior to surgery to block uptake of iodide?

Answer 34

Potassium perchlorate

Question 35

What is the long-term treatment of thyroiditis?

Answer 35

Thyroid hormone replacement

Question 36

What are the two most common forms of thyroid cancer?

Answer 36

* Papillary thyroid cancer * Follicular thyroid cancer | Medullary is very rare

Question 37

How is thyroid cancer treated?

Answer 37

* Total thyroidectomy NOTE: radioiodine treatment may also be given afterwards to kill remaining cells NOTE: high dose thyroxine may be given to suppress TSH levels to prevent TSH from stimulating any remaining thyroid cells

Question 38

What is tumour marker for thyroid cancer recurrence

Answer 38

thyroglobulin

Question 39

Which cells do medullary thyroid cancer arise from?

Answer 39

* Calcitonin-producing C cells NOTE: it is part of MEN2

Question 40

Name two tumour markers used for medullary thyroid cancer?

Answer 40

Calcitonin CEA