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?
In addition ions (I- and Na+) move into the cell via sodium-iodide symporter (NIS).
The functioning of the NIS is maintianed by the Na+/K+ ATPase which maintians the required sodium concentration gradient
Which enzyme converts iodide to iodine?
Thyroid peroxidase
How is thyroxine produced?
- TSH is secreted from anterior pituitary and binds to TSHR in follicular cell
- Binding of TSH to receptor leads to:
- production of thyroglobulin (TG) - prohormone of thyroid hormone - which travels to the colloid.
- activation of enzyme thioperoxidase (TPO) which travels to colloid
- impacts on iodine intake as well - In addition ions (I- and Na+) move into the cell via sodium-iodide symporter. Sodium gradient is maintained by sodium-potassium ATPase.
- Iodide ions cross the cell and enter the colloid via Pendrin pumps located on apical membrane (facing colloid).
- Iodide is oxidised to make iodine in colloid
- Iodine binds to tyrosine residues in TG - at position 3 and 5 - (iodination reaction of TG catalysed by TPO) making monoiodothyronine (MIT) and Diiodothyronine (DIT)
- MIT and DIT go through a coupling reaction to create thyroid hormones:
- T3 hormone (active form) —> MIT + DIT
- T4 hormone (inactive form) —> DIT + DIT
Outline the percentages of thyroxine in the blood
70% bound to Thyroxine Binding Globulin (TGB)
20% bound to thyroxine-binding pre-albumin (TBPA)
5% bound to Albumin
0.03% is free
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
Categorise the types of hypothyrodisim
List the main causes of hypothyroidism.
Hypothyroidism can be:
1. Primary –> issue lies in thyroid gland and release of thyroxine (commonest)
2. Secondary –> issue lies in pituitary and release of TRH
Main causes of Hypothyroidsm
1. Hashimoto’s Thyroiditis (autoimmune - Thyroid peroxidase autoantibodies)
2. Atrophic thyroid (congenital or acquired)
3. Post-Grave’s disease (radioactive iodine, surgery or thionamine suppression)
Outline the investigation findings that may be seen in hypothyroidism.
1. Diagnose (establish) hypothyroidism
High TSH + Low T4 (= primary hypothyroidism)
2. Establish cause
e.g. Thyroid peroxidase autoantibodies ——> Hashimoto’s thyroiditis
Remember: if 1 autoimmune condition is present – others are likely. Look for coeliac, pernicious anaemia, Addison’s.
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 and/or worsen exisitng cardiac failure
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, hence treated in patients with high cholesterol
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 (heel prick test)
Done at 48-72hr postnatally as TSH measured after 48hrs comes only form the baby.
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.
- Diagnose
* Low TSH + High T3 and T4 - Distinguish between high or low uptake hyperthyroid
* Technetium scan (high uptake = conditions with increased production of T4 vs low uptake = conditions with increased release of T4) - Establish cause
* Antibodies (e.g. TSH antibodies - Grave’s)
Outline the management of hyperthyroidism.
- Beta blocker (if pulse >100bpm)
- Thoinamides (e.g. carbimazole, propylthiouracil/PTU)
-
- Radioactive Iodine (taken up by thyroid and destroys gland due to radiation)
- Potassium Perchlorate (used if patient about to go into surgery)
Other aspects of management
o Perform ECG – make sure pt does not have AF
o Check bone mineral density – make sure pt does not have osteopenia
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
