HRR: thyroid physiology Flashcards
How are thyroid hormones stored?
Outside follicular cells in colloid
What is goiter?
An enlarged thyroid
How do we get the majority of T3?
Via peripheral conversion of T4 to T3. Some T3 is produced on its own by the thyroid gland though
Compare effects of T3 and T4.
T3 has greater effect at receptors and is more biologically potent; it is the most potent thyroid hormone
What is reverse T3?
An iodine is moved off of an inner ring and to an outer ring. It is biologically inactive
Describe the hypothalamic/pituitary/thyroid axis.
- TRH is released from hypothalamic neurons and binds to TRH receptor on thyrotrophs in the anterior pituitary. 2. Thyrotrophs produce TSH. 3. TSH travels to the thyroid. 4. Thyroid releases T4 and T3.
What is an issue with the TSH receptor?
It is very similar to LH/hCG receptors; this may lead to excessive stimulation of the TSH receptor, especially during pregnancy.
Describe T3/T4 negative feedback.
- At the hypothalamus: once enough T3/4 is produced it can saturate receptors at the hypothalamus and prevent transcription of TRH to reduce production of thyroid hormones. 2. At the pituitary: reduces the number of TRH receptors and inhibits gene transcription of a and b chains of TSH.
What is the impact of somatostatin on TSH?
Inhibits TSH secretion via decreasing pituitary response to TRH.
What happens to T3 during starvation/fasting?
T3 is decreased and reverse T3 is increased. This occurs due to decrease metabolic rate and fuel consumption to conserve energy by reducing the more potent thyroid hormone.
How does temperature impact thyroid hormone?
Cold temperature can activate thyroid axis and increase production.
What can iodine deficiency do to the thyroid?
It can cause goiter! Thyroid is working overtime, causing hypertrophy.
Describe how a lack of iodine impacts the thyroid hormones.
Without iodide, we cannot make thyroid hormones. This leads to hypothyroidism as well as an elevated TSH due to the lack of negative feedback.
What is wolff-chaikoff effect?
Acute, large doses of iodine cause short-term suppression of thyroid hormone secretion aka temporarily inhibited hormone synthesis/release. The effect is transient and only lasts a day or two.
How much of T3 and T4 is protein bound?
Pretty much all of it!
What proteins bind thyroid hormone?
TBG, albumin, transthyretin
Which binding protein has the strongest affinity for thyroid hormone?
TBG
Which binding protein has the lowest affinity for thyroid hormones?
Albumin
Does T3 or T4 have a longer half life?
T4
Describe type 1 deiodinase: what it does, where it is found.
Enzyme in the plasma membrane that catalyzes peripheral conversion of T4 to T3. Found largely in the liver and kidney, with some in the thyroid, pituitary, and skeletal muscle.
Describe type 2 deiodinase.
Enzyme in the cytosol that catalyzes peripheral conversion of T4 to T3. Largely found in glial cells/CNS, pituitary, fat, skeletal muscle, bone/cartilage, placenta.
Describe type 3 deiodinase.
Enzyme in the plasma membrane that catalyzes peripheral conversion of T4 to reverse T3. Active in the skin, CNS, placenta, etc.
What is the catalytic center for deiodinase reaction?
Selenocysteine
What makes T3 more potent?
It has really good affinity for thyroid hormone nuclear receptors in DNA, giving it a high ability to mitigate more processes.
How do T3 and T4 have their effects?
They modulate gene expression.
What are major effects of thyroid hormone?
Increased metabolic rate, increased growth, CNS development, cardiovascular autonomics.
How does thyroid hormone impact thermogenesis?
T3 particularly but also T4 increase oxygen consumption as well as heat production.
What does thyroid hormone help with in bone?
Linear bone growth and bone protein synthesis.
Which deiodinase is found in bone?
Type 2
What can happen to a child with hypothyroidism?
Low CNS development/mental age, low bone age, low height age.
How does thyroid hormone impact the heart?
Impacts resting heart rate and stroke volume via increased contractility.
How does thyroid hormone increase contractility in the heart?
Increases calcium channels, increases the number of sodium potassium pumps, increased myosin action.
How does thyroid hormone impact catecholamines?
It impacts their effects via increasing the number of catecholamine receptors (ex: b adrenergic receptors).
What is grave’s disease?
An autoimmune form of hyperthyroidism featuring TSH receptor antibody (also called TSH receptor stimulating immunoglobulins) that stimulate thyroid receptors.
What are the 3 components of grave’s disease?
Hyperthyroid symptoms, swelling of the thyroid, and possibly protruding eyes.
Why can the eyes protrude in grave’s disease?
Periorbital adipocytes and fibroblasts express TSH receptors and can bind TSHRab antibody, increasing mucopolysaccharides and inflammation in the extraocular tissue which leads to protrusion.
What are physiologic changes associated with hypothyroidism?
Lower BMR/weight gain, fatigue, cold intolerance, lower CO at rest, decreased sensory input.
What is the onset of adult hypothyroidism?
Slow developing.
What is the onset of adult hyperthyroidism?
Less delayed than hypothyroidism.
Periorbital edema is a sign of…
Hypothyroidism.
What is myxedema?
A severe form of adult hypothyroidism.
