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 of tyrosine residues in 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)
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