ChemPath: Thyroid Flashcards
What controls the uptake of iodide by thyroid follicular cells?
TSH
Which transporter is important for the transport of iodine across the cell membrane?
Na+/I- symporter
Which enzyme converts iodide to iodine?
Thyroid peroxidase
How is thyroxine produced?
- TPO iodinates ‘tyrosyl residues’ parts of the ‘thyroglobulin’ to generate monoiodotyrosine (MIT) and diiodotyrosine (DIT)
- MIT and DIT combine to form triiodothyronine (T3)
- Two DIT combine to form tetraiodothyronine (T4)
What percentage of total T4 is free T4?
0.03%
What does T4 bind to in the blood and how is it distributed?
- Thyroxine binding globulin (TBG) - 75%
- Thyroxine-binding prealbumin (TBPA) - 20%
- Albumin - 5%
Outline the hypothalamo-pituitary-thyroid axis.
- The hypothalamus produces TRH which stimulates the release of TSH from the anterior pituitary
- TSH stimulates T4 production
- T4 negatively feeds back to the hypothalamus and pituitary
List some causes of hypothyroidism.
- Hashimoto’s thyroiditis (autoimmune)
- Atrophic thyroid gland
- Post-Graves’ disease (after treatment)
- Iodine deficiency
- Postpartum thyroiditis
- Drugs (e.g. amiodarone, lithium)
- 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)
What are some clinical features of hypothyroidism?
- Weight gain with poor appetite
- Cold intolerance
- Constipation
- Fatigue
- Hyponatraemia
- Normocytic anaemia (unless pernicious anaemia)
- Myxoedema
- Goitre
Clinical features often subtle in elderly
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?
Levothyroxine (T4) - 50-125-200 µg/day titrated to a normal TSH
What are some risks of overtreatment with levothyroxine?
- Osteopaenia
- Atrial fibrillation
What is a subclinical hypothyroidism?
- Normal T4 with high TSH
- Sometimes referred to as compensated hypothyroidism
- 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 (40-60%)
- Toxic multinodular goitre (30-50%)
- Single toxic adenoma (5%)
Others: subacute thyroiditis, post-partum thyroiditis
What is post-partum thyroiditis?
- Autoimmune disease that occurs up to 1 year postpartum
- Anti-thyroid antibodies destroy thyroid follicles resulting in the release of T3 and T4
- Leads to hyperthyroidism
What is struma ovarii?
A rare form of ovarian dermoid tumour (teratoma) that contains >50% thyroid tissue and produces thyroid hormones
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 - to treat adrenergic symptoms (palpitations, tremor)
- Thionamides (e.g. carbimazole)
- Radioiodine
What is a major risks 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
(other autoimmune disease)
What is the mechanism of action of thionamides?
Inhibits TPO thus preventing the conversion of iodide to iodine as well thyroid hormone synthesis
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 definitive treatment of Grave’s and TMG?
Radioiodine
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
What genetic condition is medullary thyroid cancer associated with?
MEN2
Name two tumour markers used for medullary thyroid cancer?
- Calcitonin
- CEA
What is thyroglobulin used to monitor?
Disease reoccurance in differentiated thyroid cancer (papillary or follicular)
