ChemPath: Thyroid Flashcards
What controls the uptake of iodine by thyroid follicular cells?
TSH
Which channel is important for the transport of iodine across the cell membrane?
Na+/K+ ATPase
Which enzyme converts iodide to iodine?
Thyroid peroxidase
How is thyroxine produced?
Iodination of tyrosine residues in thyroglobulin generates MIT and DIT which leads to the formation T3 and T4
what percentage of thyroxine is free active T4?
0.03%
What does thyroxine bind to in the blood?
- Thyroxine binding globulin (TBG)
- Thyroxine-binding prealbumin (TBPA)
- Albumin
Outline the hypothalamo-pituitary-thyroid axis.
- The hypothalamus produces TRH which stimulates the release of TSH from the anterior pituitary
- TSH stimulates T3/T4 production
- T4 feeds back to the hypothalamus and pituitary
List some causes of hypothyroidism.
- Hashimoto’s thyroiditis (autoimmune)
- Atrophic thyroid gland
- Post-Graves’ disease (after treatment)
- Post-thyroiditis
- Drugs (e.g. amiodarone, lithium)
- Iodine deficiency
- Pituitary disease
- Peripheral thyroid hormone resistance
Outline the investigation findings that may be seen in hypothyroidism.
- High TSH
- Low T4
- Thyroid peroxidase antibodies
- Look out for other autoimmune conditions
Why is it important to do an ECG in patients with suspected hypothryoidism?
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?
Thyroxine (50-150-200 µg/day titrated to a normal TSH)
What are some risks of overtreatment with thyroxine?
- Osteopaenia
- Atrial fibrillation
What is a subclinical 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
Outline how 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?
Guthrie test
Why is the timing of the Guthrie test important?
It needs to be done at least 48-72 hours after birth to make sure maternal TSH is no longer in the baby
What is sick euthyroid?
- 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
What are the TFT findings in sick euthyroid?
- Low T4 and T3
- Normal/high TSH
NOTE: these patients do not have symptoms of hypothyroidism
What are the three main causes of hyperthyroidism?
- Graves’ disease
- Toxic multinodular goitre
- Single toxic adenoma
Others: subacute thyroiditis, post-partum thyroiditis
What is post-partum thyroiditis?
During pregnancy, the body may produce antibodies that stimulat the thyroid gland
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.
- Low TSH
- High T4 and T3
- Technetium scan
- Thyroid antibodies (thyroid microsomal)
Outline the management of hyperthyroidism.
- Beta-blocker
- ECG
- Bone mineral density
- Radioiodine
- Thionamides
What is a major risk of radioiodine treatment for hyperthyroidism?
- Can precipitate thyroid storm
- Can result in hypothyroidism
List some features of Graves’ disease.
- Diffuse goitre
- Thyroid-associated ophthalmopathy
- Pretibial myxoedema
- Thyroid acropachy
NOTE: radioiodine can make Graves’ eye disease worse
What is the mechanism of action of thionamides?
Prevents the conversion of iodide to iodine by thyroid peroxidase
What is a rare but important side-effect of thionamides?
Agranulocytosis
NOTE: patients should be advised to stop treatment if they develop a sore throat or fever
What kind of dosing regimes can be used for thionamdes?
- 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 to block uptake of iodide?
Potassium perchlorate
What is the long-term treatment of thyroiditis?
Thyroid hormone replacement
What are the two most common forms of thyroid cancer?
- Papillary thyroid cancer
- Follicular thyroid cancer
How is thyroid cancer treated?
- Total thyroidectomy
NOTE: radioiodine treatment may also be given
NOTE: high dose thyroxine may be given to suppress TSH levels to prevent TSH from stimulating any remaining cells
Which cells do medullary thyroid cancer arise from?
- Calcitonin-producing C cells
NOTE: it is part of MEN2
Name two tumour markers used for medullary thyroid cancer?
Clacitonin
CEA
