ChemPath: Thyroid
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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