Thyroid gland Flashcards
What is the functional unit of the thyroid gland?
Thyroid follicle
-surrounded by epithelial follicular cells and parafollicular cells (that secrete calcitonin in response to increased Ca), filled with colloid
How much thyroid hormone is secreted per day?
60 ug/day
-the body can hypothetically last 2-3 months with the amount stored in the Thyroid gland
Why is more T4 produced than T3?
10x faster reaction speed
Why is T4 peripherally converted to T3? How does this occur?
T3 is the major active hormone, occurs with a deiodinase (type 1 in periphery[80-90%] and type 2 in CNS)
What does “I trap” refer to?
The Na+/I- symporter that actively transports I- into the follicular cell. Stimulated by low I- levels in the body
What are the competitive inhibitors to I-trap?
Thiocyanate and perchlorate
How does I- get to the colloid?
Through pendrin (channel that allows I2 out in conjunction with Cl-) after I- is converted to I2 by thyroid peroxidase
What does peroxidase do?
- Oxidizes I- to I2
- Organification of I2 into thyroglobulin
- Coupling reactions (MIT+DIT or DITx2)
What inhibits thyroid peroxidase? and what can it treat?
Propylthiouracil (PTU) at all three steps
PTU can be a good treatment for hyperthyroidism
What is the Wolff-Chaikoff effect?
High levels of I- that inhibit organification and synthesis of thyroid hormone
How do T3/T4 get out of the colloid when the thyroid gland is stimulated?
Iodinated thyroglobulin is endocytosed into follicular cell. T4 and T3 are then hydrolyzed via lysosomal proteases and transported across the basal membrane to nearby capillaries
What happens to the leftover thyroglobulin/MIT/DIT once inside the follicular cell?
MIT and DIT are deiodinated via thyroid deiodinase to recycle the iodide and tyrosine molecules
What is pendred syndrome?
When pendrin pump not working thyroid hormone synthesis is affected = hypothyroidism. Cochlea also affected = sensorineural hearing loss.
What are the main thyroid hormone binding proteins?
Thyroxine-binding globulin (TBG) - higher affinity for T4
Transthyretin (TTR) - in brain
Albumin
Most circulating TH is T4–1/2 life of 6 days compared to T3’s 1 day
What is the T3 resin uptake test?
Can indirectly assess circulating levels of TBG. TBG has multiple binding spots for T3/T4. Add unbound and labeled T3 to solution and let it bind to unbound TBG sites. Measure T3 uptake which tells how much of the labeled T3 did not bind to TBG
What does high T3 uptake in the resin test mean?
Hyperthyroidism: high T4 so more bound to TBG = less spots for T3 binding
What does low T3 uptake in the resin test mean?
Hypothyroidism: low T4 so more T3 bound to TBG = less uptake
Where is TBG synthesized?
In the liver
What happens to TBG and T3/T4 levels during liver failure?
Low TBG synthesis (since it’s made in liver) = transient increase in free T3/T4 levels = negative feedback to thyroid = decreased T3/T4 synthesis
What happens to TBG levels during pregnancy?
They are increased because high estrogen is a modulator in liver for binding protein formation.
What does it mean if a patient is ‘clinically euthyroid’?
During pregnancy there is an increase in TBG = increased levels of bound T3/T4 causes increase secretion of T3/T4. Levels of free T3/T4 still normal though
What is TSH secretion like compared to GH secretion?
Steady rate rather than pulsatile
What is the second messenger for TSH?
cAMP
What are the two actions for TSH on the thyroid gland?
Increase synthesis/secretion of thyroid hormones and trophic effect on thyroid gland (growth)
What are some of the actions of thyroid hormones?
Growth, bone maturation, maturation of CNS (more dendrites and synapses), increase in Na-K ATPases, increase heat production and BMR, increased O2 consumption, increased glucose absorption, increased lypolysis, increased cardiac output
-also direct the formation of beta1-adrenergic receptors, lysosomal enzymes, transport and structural proteins to perform the actions
How do thyroid hormones increase BMR?
Due to increased activity of Na-K ATPase (increased O2 consumption and heat production)
What can deficiency of thyroid hormones during perinatal period lead to?
Congenital hypothyroidism leading to abnormal development of synapses and decreased dendritic branching and myelination
What is Hashimoto’s thyroiditis?
The most common cause of hypothyroidism in iodine-sufficient areas, caused by autoimmune gland destruction by anti-thyroid antibody. High TSH levels and low T3/T4.
Why can patients with Hashimoto’s thyroiditis have a goiter?
Low T3/T4 levels increase TSH secreted by pituitary which has a trophic effect on the thyroid gland
What is Sheehan syndrome?
Postpartum hypopituitarism due to necrosis of pituitary gland
- women present w/ the inability to produce milk, lactate, or menstruate
- can have hypothyroidism and other endocrine issues
What are a few of the reasons T4 might not be converted to T3 clinically?
- body is Fasting
- increased stress (could be due to surgery)
- certain Catabolic diseases
What would a mutated Pendrin gene result in?
Faulty transport across the apical membrane (I- being converted to I2 moving across)
Also affects the cochlea—sensorineural hearing losses
Predred Syndrome patients present with hypothyroidism w/ goiter
Why is the effect of Thyroid hormones on Lipid metabolism important?
They stimulate fat mobilization–>plasma [fatty acids]^
-the conversion of carotene to vitamin A relies on this mechanism ([cholesterol and Triglycerides] in plasma inversely proportional to TH)
Patients with Hypothyroidism can suffer from blindness and yellowing skin due to the increased [cholesterol] in the blood
What is the politically correct term for Cretinism, and how does that occur?
Congenital Hypothyroidism
-Deficiency of Thyroid hormone during the perinatal period (22 weeks-about 1 week post-birth) causes neural changes
condition of severely stunted physical and mental growth
Would TSH levels be increased or decreased in Grave’s disease? why?
What is the big difference in secondary hyperthyroidism?
Decreased…the Thyroid Hormone levels are raised in circulation, causing negative feedback inhibition of TSH secretion
Secondary- involves defects in the hypothalamus or pituitary (TSH secreting tumor)
-if something is wrong with the Anterior pituitary, TSH will be increased
What might an iodine deficiency cause? (thyroid-wise)
Hypothyroidism— leads to transient decrease in TH, which of course leads to more TSH secretion, naturally presenting with a goiter
-“euthyroid” and assymptomatic if the glands are able to maintain a normal level of thyroid hormones
