ChemPath 9: Thyroid Flashcards
What controls the uptake of iodine by thyroid follicular cells in the thyroid gland? where is this made?
TSH from the pituitary gland
What needs to be done to iodine that is taken up in the GIT?
Needs to be converted to iodide as this is what is taken up by thyroid gland
Which channel is important for the transport of iodide across the cell membrane?
Iodide is actively taken up into thyrocytes via a Na+/K+/ATPase pump
How is thyroxine produced?
Thyroglobulin = protein in thyroid gland
Iodide that has been taken up is converted to iodine via thyroid peroxidase
Iodine + thyroglobulin -> MIT, DIT and eventually T3 and T4
Where is thyroxine stored once produced?
Once thyroxine (T4) is produced, it is stored inside the thyroid gland colloid
What percentage of thyroxine is free active T4?
0.03%
What does thyroxine bind to in the blood?
Which is main + when might it be low?
Thyroxine binding globulin (TBG) - 75% = MAIN (based on albumin synthesis hence if albumin is low -> TBG low)
Thyroxine-binding prealbumin (TBPA) = 20%
Albumin = 5%
Outline the hypothalamo-pituitary-thyroid axis
The hypothalamus produces TRH (thyrotrophin releasing hormone) which stimulates the release of TSH (thyroid stimulating hormone) from the anterior pituitary
TSH stimulates T3/T4 production
T4 feeds back to the hypothalamus and pituitary
(Good image on notion)
List some causes of hypothyroidism.
Hashimoto’s thyroiditis (autoimmune) = MOST COMMON CAUSE
Postpartum-thyroiditis
Atrophic thyroid gland
Iodine deficiency (CAUSE IN DEVELOPING WORLD)
Pituitary disease
Peripheral thyroid hormone resistance
Post-Graves’ disease (after treatment)
Drugs (e.g. amiodarone, lithium)
Outline the investigation findings that may be seen in hypothyroidism.
High TSH + Low T4 = Primary hypothyroid
Thyroid peroxidase antibodies (suggests autoimmune)
Look out for other autoimmune conditions (eg. pernicious anaemia, coelic and addisons)
Why do ECG in patients with suspected hyopothyroidism?
What should you do?
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
How is hypothyroidism treated?
Risk of overtreatment?
Levothyroxine (T4 - 50-125-200 µg/day titrated to a normal TSH)
Overtreatment can cause osteopaenia & AF
Patients may want to take too much as it can help them lose weight
What is subclinical hypothyroidism? AKA?
When might these pts be more likely to develop hypothyroidism?
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
Why might there be some benefit to treating subclinical hypothyroidism?
Hypothyroidism is associated with hypercholesterolaemia
How does thyroid function changes in pregnancy?
hCG has a similar structure to TSH so high hCG levels can cause hyperthyroidism
Free T4 levels rise slightly
TBG level increase dramatically
NOTE: hCG level drops later on in pregnancy
How is neonatal hypothyroidism diagnosed? - What component is tested for?
What is the timing and why?
Guthrie test - Looking at TSH
It needs to be done at least 48-72 hours after birth to make sure maternal TSH is no longer in the baby
What happens if neonatal hypothyroid is tested too early / too late?
Too early = ridiculously high due to maternal TSH
Too late = untreated hypothyroidism which can lead to intellectaual problems in later life
What is sick euthyroid?
Alteration in the pituitary thyroid axis in non-thyroidal illness (can happen in any severe illness)
In other words, when you are very sick, your thyroid will shut down to try and reduce your basal metabolic rate
Biochemical findings in sick euthyroid?
Low T4 and T3
Normal/high TSH
NOTE: these patients do not have symptoms of hypothyroidism + giving thyroxine will not improve their symptoms
What are the three main causes of hyperthyroidism?
Others?
- Graves’ disease (40-60%)
- Toxic multinodular goitre / Plummers disease (30-50%)
- Single toxic adenoma (5%)
Others: subacute thyroiditis, post-partum thyroiditis,
What is post-partum thyroiditis?
During pregnancy, the body may produce antibodies that stimulate the thyroid gland
After the child is born, the thyroid gland is attacked by these antibodies - → hyperthyroidism as stored thyroid hormone is released
Thyroid hormone stores used up → patient becomes hypothyroid → patient becomes euthyroid
What is struma ovarii?
A rare form of ovarian tumour (usually a teratoma) that contains mostly thyroid tissue and produces thyroxine
List some investigation findings of hyperthyroidism.
TFTs = Low TSH, High T4 and T3
Thyroid antibodies (thyroid microsomal antibodies =anti-TSH) - seen in graves
Technetium scan
What is a technetium scan used for in thyroid disease?
Causes of high / low uptake?
A Technetium scan can be used to see which parts of the thyroid are producing excessive thyroid hormone
High:
- Grave’s
- Toxic multinodular goitre
- Single toxic adenoma
Low:
- Subacute thyroiditis
- Post-partum thyroiditis
Mx of hyperthyroidism?
Symptomatic:
B-blocker - tachycardia
ECG - ensure no fast AF
DEXA / bone mineral density scan - exclude osteoporosis / osteopaenia
Thionamides (Carbimazole, propylthiouracil) - can reduce T3 and T4 production
Radioiodine + surgical removal of gland - if persistently high despite thionamide use
What is a major risk of radioiodine treatment for hyperthyroidism?
Can precipitate thyroid storm (release of thyroxine from gland)
Can result in hypothyroidism
Features of Graves disease?
Why is there a need to be careful of radioiodine use?
Diffuse goitre
Thyroid-associated ophthalmopathy
Pretibial myxoedema
Thyroid acropachy - skeletal abnormality
NOTE: radioiodine can make Graves’ eye disease worse
MoA of thionamides?
Examples?
Prevents the conversion of iodide to iodine by thyroid peroxidase
Carbimazole, propylthiouracil
What is a rare but important side-effect of thionamides?
Mx re this?
Agranulocytosis
Patients should be advised to stop treatment if they develop a sore throat or fever
What kind of dosing regimes can be used for thionamides?
Can be titrated to achieve normal T4 levels
Block and replace – high dose is given to block the thyroid gland and then given thyroxine replacement
Which drug can be given to hyperthyroid patients prior to surgery?
Why is this given?
Potassium perchlorate
To prevent uptake of iodine into thyroid cells
What are the different types of thyroiditis?
Subacute / viral thyroiditis / De Quervains thyroiditis
Post-partum thyroiditis
Silent thyroiditis - immune and amiodarone caused
Pathophysiology of Subacute/ viral thyroiditis/ De Quervain’s Thyroiditis?
This is where someone has a thyroid illness
Virus attacks the thyroid gland → patient first presents with hyperthyroidism as stored thyroid hormone is released
Thyroid hormone stores used up → patient becomes hypothyroid
Once virus clears → patient becomes euthyroid
What is the long-term treatment of thyroiditis?
Thyroxine replacement
What are the two most common forms of thyroid cancer?
Tumour marker + what is this used for
Differentiated thyroid carcinoma:
- Papillary thyroid cancer
- Follicular thyroid cancer
Thyroglobulin - monitoring relapse following mx
What is a rare but devastating thyroid cancer?
Which cells do they arise form? What condition can this be part of?
Medullary Thyroid Carcinoma
Calcitoning-producing C cells of the thyroid gland
Can be part of MEN2
Mx of Differentiated thyroid carcinoma?
What can be given as adjuncts?
Total thyroidectomy
radioiodine treatment may also be given
high dose thyroxine may be given to suppress TSH levels to prevent TSH from stimulating any remaining cells
Name two tumour markers used for medullary thyroid cancer?
Calcitonin
CEA
Try cases on the notion
OKAY!
