PHYS - Thyroid Gland Flashcards
What is T4?
Tetraiodothyronine is a prohormone synthesized by the thyroid gland
What is T3?
Triiodothyronine is an active hormone synthesized by the thyroid gland
What are parafollicular C cells?
Cells outside the follicles of the thyroid gland that secrete Calcitonin
Which cells synthesize the thyroid hormones?
Follicular epithelial cells that surround the follicles containing colloid
What is colloid composed of?
Colloid is composed of newly synthesized thyroid hormones attached to thyroglobulin
What is the ratio of synthesized thyroid hormone (T4:T3)
T4:T3
10:1
What is the enzyme responsible for converting T4 into T3?
Deiodinase enzyme
What is the inactive form of T3?
Reverse T3 is inactive
It has an iodine missing from the wrong benzene ring
1% of synthesized thyroid hormone is made into Reverse T3
What are the sources of T3?
80-90% of T3 is produced via peripheral conversion (via deiodoinase)
10-20% of T3 is directly secreted from the thyroid gland
What can cause a decrease in conversion of T4 to T3?
Fasting
Medical and Surgical stress
Catabolic disease
What is the NIS channel?
It is a Na+/I- symporter on the apical membrane of the follicular cells of the thyroid gland
It transports 2 Na+ for every I-
It is also called the Iodine trap
What are Pendrin channels?
They are channels found on the basolateral membrane of the follicular cells of the thyroid gland
They are responsible for secreting I- anions into the thyroid follicles
What is the role of Thyroid peroxidase?
Thyroid Peroxidase is an enzyme that takes two Iodide (I-) anions and forms molecular Iodine (I2)
Molecular I2 can be added MIT/DIT/Thyroglobulin in the follicle to form the colloid
What specifically does TSH do to follicular cells?
TSH stimulates pinocytosis of colloid fluid into the follicular cell which then gets acted on by proteases (lysosomes) to remove the T3 and T4 from the thyroglobulin molecule
T3 and T4 are then secreted into the blood
What is thyroglobulin?
Thyroglobulin is a binding protein that is synthesized in the follicular cells of the thyroid gland.
It is translated in the rough ER and packaged in the Golgi before being secreted into the follicle
Thyroglobulin binds to MIT, DIT, T3, and T4 in the follicle. The collection of thyroid hormone and its precursors bound to thyroglobulin is what makes up the colloid fluid
Describe the process of thyroid hormone synthesis and secretion
NIS Channel (iodine trap) on the basolateral membrane (facing the blood) brings in one I- anion with two Na+ cations into the follicular cell
Thyroglobulin binding protein is synthesized in the follicular cell and secreted into the follicle
Pendrin channel on the apical membrane (facing the follicle) is an I- anion channel that sends I- into the follicle
Peroxidase enzyme takes two I- anions to form molecular Iodine (I2)
Molecular I2 binds with MIT (to form DIT), DIT (to form T3), and T3 (to form T4)
MIT, DIT, T3, and T4 bind with thyroglobulin binding molecules in the follicle forming the colloid
TSH signaling induces Follicular cells to conduct pinocytosis of the colloid fluid.
Thyroglobulin molecules collected in the follicular cells from pinocytosis interact with proteases to break down the binding proteins, freeing up the thyroid hormone molecules for secretion.
MIT and DIT do not get secreted; instead they interact with deiodinase enzymes, which remove the iodoine molcules from MIT and DIT in order to be recycled back into the follicle
What is PTU?
Propylthiouracil
It is a drug that is used to treat hyperthyroidism
PTU blocks the actions of thyroid peroxidase, therefore inhibiting the oxidation of iodide (I-) anions into molecular Iodine
What is the function of Perchlorate and Thiocynate?
Perchlorate and Thiocynate are drugs that block the NIS channel on the basolateral membrane of the follicular cells of the thyroid gland, preventing Iodine uptake from the blood into the cell
What happens to thyroid hormone synthesis when iodide availability is restricted?
T3 is favored over T4
How is thyroid gland activity assessed?
Radioactive iodine uptake test
In what state does thyroid hormone travel in the blood?
99% bound to plasma proteins
1% free
How do the half lives of T3 and T4 compare?
T4 has a greater half life than T3
T4 = 6 days T3 = 1 day
What are the main binding proteins that carry thyroid hormone in the blood?
TBG (Thyroxine-binding Globulin) - 70%
- Synthesized in the liver
- Has a higher affinity for T4 than T3
Transthyretin (TTR) - 10-15%
Albumin - 15-20%
What happens to T4 when it is delivered to the tissues?
T4 is a prohormone
T4 is converted to the active form of thyroid hormone, T3, in the tissues
OR sometimes it is converted to reverse T3 (inactive)
How does a T3 resin uptake test work?
A known amount of labelled, free T3 is added to blood.
T3 will bind to TBG as long as there are unboundsites available
Once all sites are filled, anti-T3 antibodies are added and precipitate out of solution.
This allows you to determine the amount of TBG in the blood
What happens to TBG levels in hepatic failure and what effect does this have on thyroid hormone function?
Hepatic failure decreases blood levels of TBG (which is synthesized in the liver
This causes an increase in levels of free T3 and T4
Increased levels of free T3,T4 provide negative feedback, inhibiting thyroid hormone synthesis
What happens to TBG levels during pregnancy, and what effect does this have on thyroid hormone funtion?
TBG levels increase during pregnancy
This causes a decrease in levels of free T3,T4
Decreased levels of free T3,T4 promote thyroid hormone synthesis and secretion
Total levels of T3, T4 increase, but levels of free T3,T4 remain normal
What type of receptor does TSH interact with?
GPCR - specifically Gs
Activates Adenylyl cyclase, which causes an increase in cAMP, which activates PKA, which phosphorylates target proteins
What is the Wolff-Chaikoff effect?
An inhibitory effect on thyroid hormone synthesis due to excessive Iodine intake
What action of thyroid hormone is primarily responsible for the increase in basal metabolic rate?
Thyroid hormones cause an increase in synthesis of Na-K-ATPase channels, which are primarily responsible for the increase in BMR seen with Thyroid Hormone
What affect does thyroid hormone have on cardiac tissue?
Increases heart rate and cardiac output
Promotes synthesis of cardiac Beta-adrenergic receptors making the cardiac tissue more sensitive to sympathetic innervation
What is the pathophysiology of hyperthyroidism?
Metabolism:
- Heat intolerance
- Weight loss
- Increased BMR
Bone:
- Osteoperosis
CNS:
- Agitation
- Anxiety
- Difficulty concentrating
- Hyperreflexia
Skin:
- Sweating
CV System:
- Tachycardia
- Atrial Fibrulation
- Palpitations
- High-output cardiac failure
Intestine:
- Diarrhea
What is the pathophysiology of hypothyroidism?
Metabolism:
- Cold intolerance
- Weight gain
- Decreased BMR
Bone:
- Stunted growth
CNS:
- Slowed movement
- Impaired memory
- Decreased mental capacity
Skin:
- Dry
CV System:
- Bradycardia
- Decreased contractility
- Decreased cardiac output Heart Failure
Intestine:
- Constipation
What is Primary Hyperparathyroidism vs Secondary Hyperthyroidism?
Primary = Graves Disease - Excessive secretion of TH from the thyroid gland (TSH levels will be decreased due to negative feedback)
Secondary = Excessive secretion of TSH from the anterior pituitary gland
What is Grave’s Disease?
Thyroid Stimulating Immunoglobulins (TSIs) that are analogous to TSH will stimulate the TSH receptor on the thyroid gland promoting synthesis and secretion of TH despite lack of actual TSH signaling from the anterior pituitary gland
Major clinical signs:
- Exophthalmos (protrusion of eyeball)
- Periorbital edema
What is Sheehan’s syndrome?
Hypothyroidism due to pituitary necrosis secondary to blood loss during or after delivery of baby (no TSH secretion from anterior pituitary, and therefore no TH secretion from thyroid gland)
How do you treat hypothyroidism?
T4 supplementation
In older women, over prescribing T4 supplements can cause osteoporosis
What is Hashimoto’s Thyroiditis?
Autoimmune disorder
Antibodies produced to fight against Thyroglobulin protein in colloid or Thyroid Peroxidase enzyme
Prevents synthesis of Thyroid hormone
Excessive TSH secretion occurs, causing production of a goiter
What is cretinism?
Cretinism is congenital hypothyroidism
Caused by iodine deficiency, impaired development of thyroid gland
Symptoms:
- Mental retardation
- Growth retardation
- Dry skin
- Protruding tongue
- Respiratory difficulty
- Feeding problems
What causes goiters?
TSH receptor activation causes hypertrophy of thyroid gland (goiter)
Anyway TSH receptor is activated excessively will cause a goiter, whether or not it is TSH that is activating it
(Graves disease causes goiter even though it is an Immunoglobulin that activates the TSH receptor, not actual TSH)
