Lecture 29: Thyroid Gland Pharmacology Flashcards
What classes does the thyroid gland release?
- T3 (triiodothyronine) and T4 (thyroxine) thyroid hormones
* Calcitonin
What is the most active thyroid hormone?
T3 (triiodothyronine)
What causes the release of TSH from the anterior pituitary?
The release of TRH from the hypothalamus
What is TRH and what does it do?
A hormone released from the hypothalamus that stimulates TSH to be released from the anterior pituitary
What does TSH do?
It is released from the anterior pituitary and causes the release of T4 and T3 from the thyroid
What inhibits the release of TRH from the hypothalamus?
T4 and T3 from the thyroid
What inhibits the release of TSH from the anterior pituitary?
T4 and T3 from the thyroid
What are the physiological effects of T4 and T3?
- Increased basal metabolic rate
- Sensitization to catecholamine (increased cardiac output, heart rate, breathing rate)
- Important role in growth and development
What are Thyroid hormones made up of?
Two modified tyrosine molecules
What is the precursor protein to Thyroid hormone and what is it rich in?
Thyroglobulin and it is tyrosine rich
What happens to the tyrosines to make thyroid hormones?
- They are enzymatically iodinated
* The iodinated tyrosines are enzymatically coupled
What does TSH stimulation do?
Causes the thyroid hormone precursor protein to be endocytosed and processed. And then T4 and T3 can be released
Where does Iodination and coupling of thyroglobulin happen?
On the Apical side (follicle lumen)
Where is Thyroglobulin processed after it has been iodinated and coupled?
Within the cell (so not the lumen of the follicle)
Where are T4 and T3 released from after being generated from thyroglobulin?
The basolateral side of the cell, so to the bloodstream
What are thyroid follicles?
Rings made up of multiple cells that form around a lumen
What do the thyroid cells release into the follicle?
Thyroglobulin
What does Thyroperoxidase do?
It iodinates and couples Thyroid hormone
What happens if the thyroid is inactive?
The lumen of the gland will fill with colloid
What is Colloid?
Fluid that is rich in unprocessed thyroglobulin that is waiting for the signal to be processed
What does TSH trigger?
Exocytosis of thyroglobulin so it can be processed into T3 and T4
How does the the Thyroid gland get iodine?
It concentrates iodine from the bloodstream using the Na+/I- cotransporter
Where is Iodide transported?
To the follicle lumen and eventually added to thyroglobulin
What kind of receptor is the thyroid hormone receptor?
An intracellular type receptor
What does the thyroid hormone receptor do after binding of thyroid hormone?
Acts as a transcription factor after binding of thyroid hormone
What do T3 and T4 need to do in order to bind the Thyroid hormone receptor?
They need to be taken up into cells by a transporter protein (instead of just diffusing through the membrane) in order to access the receptor
Where is the receptor for T3 or T4 located?
In the nucleus already bound to transcription factors
What happens with at rest/unbound thyroid hormone receptors?
They associate with response elements and recruit co repressors which weakens gene transcription
What happens if T4 is taken up into a cell?
T4 is typically de-iodinated to form T3
What does T3 binding in the nucleus cause?
It causes recruitment of RAR (retinoic acid receptor) to form a heterodimer with the thyroid hormone receptor
What does the recruitment of coactivators when T3 is bound do?
Leads to enhanced transcription of gene
How fast is T3 and T4 activation of receptors?
It is slow
What is Hypothyroidism?
Deficient thyroid function (not enough release of thyroid hormone)
What are the most common causes of Hypothyroidism?
- Iodine deficiency (dietary)
- Autoimmunity towards thyroid (Hashimoto’s thyroiditis)
- Congenital defect
- Inappropriate hormonal regulation (insufficient TSH or TRH)
What are the symptoms of Hypothyroidism?
- Fatigue
- Weight gain
- Hypersensitivity to cold
- Bradycardia
What are the two types of Hypothyroidism?
Primary and Secondary hypothyroidism
What causes primary hypothyroidism?
Defect in thyroid function
What are the features of Hypothyroidism? (hormone levels)
Low T4 and T3 but high TSH
What is the cause of Secondary Hypothyroidism?
•Central defect (poor function of anterior pituitary or hypothalamus)
What are the feature of secondary hypothyroidism?
- Low T4 and T3
* Low TSH
Why does secondary hypothyroidism have low Low TSH and the other one has high TSH?
Because in primary hypothyroidism the gland is not producing enough T4 and T3 so there is no negative feedback inhibiting TSH. In Secondary hypothyroidism, the CNS us unable to release TSH
What is the treatment for Hypothyroidism?
Hormone replacement with Synthetic thyroxine (levothyroxine)
What is Hyperthyroidism?
Overactive Thyroid function (excessive production of thyroid hormone)
What are the most common causes of Hyperthyroidism?
- Graves disease
* Hyperplasia of the thyroid
What is Graves disease?
When stimulatory antibodies are released against the TSH receptor and activates them leading the excess thyroid hormone release
What are the symptoms of Hyperthyroidism?
- Sleep difficulty
- Heat (temperature) intolerance
- Tachycardia
- Weight loss
- Tremor
What is Graves disease caused by?
Stimulation of thyroid by anti-TSH receptor antibodies
What are the features of graves disease? (Hormones)
- High T4 and T3
- Low TSH
- Detection of anti-TSH antibodies
- Bulging eyes
What is Thyroid hyperplasia caused by?
Thyroid adenoma, goiter
What are the features of Thyroid Hyperplasia? (hormones)
- High T4 and T3
* Low TSH
What is the cause of Secondary Hyperthyroidism?
Central defect (excessive production of TSH by anterior pituitary)
What are the features of Secondary Hyperthyroidism? (hormones)
High T4 and T3 and high TSH
What are the two Thyroid Autoimmune diseases?
Graves disease and Hashimoto’s disease
What happens in graves disease?
The antibodies cause stimulation of the TSH receptor
What happens in Hashimoto’s thyroiditis?
Antibodies recognize other thyroid-specific proteins and lead to damage of the thyroid
What happens to the cells around the follicle when they become active?
The cells around become larger and the lumen becomes smaller
What happens to the follicle in graves disease?
Hyperstimulation of the follicles and so they look like an active state where the cells are big and the lumen will shrink and all the colloid is used up and spit out as thyroid hormone
What happens to the follicles in Hashimoto’s thyroiditis?
Lymphocytes infiltrate the thyroid gland that attack the thyroid follicle and cause it to die
What are some of the physical features of Hyperthyroidism?
- Exophthalmos (bulging eyes)
* Goiter (swelling in the neck)
What are the four treatments of Hyperthyroidism?
- Surgery
- Radioactive iodine treatment
- Antithyroid drugs
- Symptomatic treatment with beta-blockers
What is the drawback to using surgery to treat hyperthyroidism?
- It can disrupt the parathyroid glands causing disturbances in Ca2+
- It needs management for hypothyroidism
What is the approach for radioactive iodine treatment for Hyperthyroidism?
Iodine is concentrated within the thyroid and radiation leads to the destruction of the thyroid
What are the drawbacks to radioactive iodine treatment?
It should not be used during pregnancy
What is the approach to anti-thyroid drugs to treat hyperthyroidism?
They prevent several steps in T4/T3 synthesis
What are the drawback to anti-thyroid drugs?
They have diverse side effects
What is the approach to Symptomatic treatment of hyperthyroidism with Beta-blockers?
They may help with issues such as tachycardia
What is the drawback to treatment of hyperthyroidism with betablockers?
It does not influence the underlying cause of the disease
What is a drug to treat hyperthyroidism?
Thioamides (Methimazole)
What is Methimazole used to treat?
Hyperthyroidism
How does Methimazole work?
It prevents the iodination and coupling steps mediated by Thyroperoxidase
