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