Lecture 5 - Thyroid Flashcards
What do we see in thyroid cancer?
Parafollicular cells secrete calcitonin, large amounts of this secreted with cancer - Medullary cancer (tumour marker)
Differentiated thyroid cancer cells - produce thyroglobulin - this is a tumour marker in blood (also thyroiditis, goiter)
How does iodine get to become thyroid hormones?
- Iodine transported into cell (iodine sodium transporter) from blood stream
- Iodine is attached to thyroglobulin with thyroid peroxidase enzyme at lumen interface (inhibited by carbimazole) to form MIT and DIT
- MIT and DIT will join and can form T3 and T4 (in the colloid)
- get endocytosis of colloid to bring T3 and T4 into the cells - fuse with lysosome
-Then T3 and T4 will separate from thyroglobulin in the follicular cells, and be released back into the bloodstream (under TSH regulation)
T3 - active form
T4 - mainly stored in thyroid as this
-Most bound to thyroid binding globulin and albumin in blood
What does carbimazole do?
Can block dietary iodine getting into the cell
Used to treat an overactive thyroid gland
- Tyrosine residues will become iodinated to become thyroglobulin by thyroid peroxidase enzyme
- carbimazole can inhibit this
Storage and release of thyroid hormone
- Thyroid hormone release involved endocytosis of Tg from follicular space
- degrade Thyroglobulin then form T4 and T3
Regulation of thyroid hormone?
Hypothalamus - TRH
Pituitary - TSH
Thyroid - will bind to receptors and cause production of TG, iodine trapping and T4 and T3 synthesis
-also increases endocytosis of colloid, proteolysis of TG and therefor an increase in T4 and T3 secretion
-T4 and T3 will have negative feedback to the pituitary and hypothalamus
hypothyroidism
Weight gain, cold, hair loss nad dry skin, consitpation, tired, odemea
-Low T4, T3 - high TSH
Thyrotoxicosis
-symptoms
signs
causes
Low TSH, high T4, T3.
-symptoms - nervous, increased sweating, weight loss, heat sensitivitiy, tachycardia, weakness
Signs - goitre, skin changes, tremor, eye signs
Causes - graves disease - autoimmune production of an antibody that stimulates TSH receptor
- Multi nodular goitre - hyper functioning regions of the thyroid gland, not suppressed by circulating thyroid hormone
- thyroiditis
Thyrotoxicosis
- too much Thyroid hormone in body - treatment can be radioactive iodine (causes dry eyes and mouth), also can treat with TPO enzyme
- low TSH and high T4, T3
- symptoms nervous, increased sweating, heat sensitivity, tachycardia, weakness
- signs goiter, skin changes, tremour, tachycardia
- Causes - graves disease - autoimmune production of antibody that stimulates TSH receptor
- Cause - mulitnodular goitre, hyper functioning regions of thyroid gland, not suppressed by circulating hormone
- also can be casued by throiditis
thyroid hormone resistance syndrome
receptor mutations lead to pituitary insensitivity to T3, so tsh rises and causes rise in t4 and t3. -patient can presnet with hypo or hyperhtyroid features in different tissus and may have goiter
Thyroditiis
- inflammation of thryoid gland (pre formed thyroid homrone is dumped from lumen with thryoglobulin)
- patient presents as thyrotoxic, then has a hypothyoid phase and usually recovers
- ciruclating thyroglobulin is increased and serves as a tumour maker
Primary hypothyrodisim
high TSH, low T4, postive TPO antiboides
- Hashimotos disease
- audlt onset
- decrease in energy metbaolism, low basal metabolic rate, slightly low body temp
- decreased protein synthesis
- weight gain, cold, hair loss, dry skin