Pathophys
What do thyroid hormones help regulate?
metabolism, protein synthesis, bone growth, growth and development, many other processes
What is the role of thyroid peroxidase?
in combo with hydrogen peroxide, oxidize iodide
the iodide then enters the colloid
What facilitates T4 to become T3? (describe location of each type)
5-deiodonase removes an "I"
Type 1: in liver and kidney, responsible for most T3 in peripheral organs, often unregulated in hyperthyroidism
Type II: in heart, skeletal muscle, CNS, fat, thyroid and pituitary
In primary hypothyroidism, how are the T4/3, TSH, and TRH levels effected?
T4/3 decreased
TSH and TRH increases
When is iodine used to treat hypothyroidism?
Only in cases where iodine deficiency is the cause
Given as oral iodine preparation or increased intake of iodated foods
What is in the follicle lumen?
Colloid, which contains thyroglobulin (Tg)
Tg is a protein precursor of thyroid hormones
What does oxidized iodide react with and what is formed?
Tg to form iodotyrosines
either monoiodotyrosine or diiodotyrosine
Why is it important that we measure free (unbound) thyroid hormones?
majority is protein bound
How does iodine deficiency effect thyroid function?
initially, thyroid gland conserves iodine and increases extraction of iodine from the circulation
over time, enlargement of thyroid gland occurs, TSH increases due to lack of circulating thyroid hormone
eventually there is little to no production of thyroid hormones
tiredness, weakness, lethargy, constipation, dry skin, cold, hair loss, weight gain, dyspnea, maybe goiter, cool extremities, bradycardia, peripheral edema
myxedemic coma: extremely rare but life threatening, usually follows a precipitating event
parafollicular cells
produce and secrete calcitonin
What are the iodothyronines? How are they formed?
T3: formed by coupling MIT and DIT
T4: formed by coupling DIT and DIT
What kind of receptors do thyroid hormones typically act on? By what method does circulating thyroid hormones enter peripheral cells?
nuclear receptors: TR alpha and beta
passive diffusion
Once TRH is synthesized, what is the cascade that follows?
TRH binds to TRH receptor on thyrotropes in the anterior pituitary
TSH is released from thyrotropes and binds to TSH on thyroid follicular cells, causes increase in thyroid hormone cleavage and secretion and increases thyroid hormone synthesis
What are desiccated thyroid preparations? What are combination products?
extracted from beef or pork thyroid glands, contains both T3 and T4
these products are typically avoided due to non physiologic ratios of T3 and T4 and because synthetic products are relatively cheap and standardized
combo products: T3 and T4, no substantial benefit to this product, use should likely be avoided
Where is thyroglobulin synthesized? What happens after translation?
thyroid follicular cells
After translation, Tg is glycosylated and incorporated into vesicles and released into colloid lumen
What is the process for T3 and 4 getting released into the bloodstream?
TSH binds to the TSH receptor and signals the endocytosis of colloid from the follicular lumen
Colloid droplets fuse with lysosomes, which contain proteolytic enzymes necessary to liberate T4 and 3
What is the main role of T3 in the body? How does it achieve it?
modulate gene transcription which leads to increased or decreased protein synthesis
T3 binding causes dissociation of the co-repressors and facilitates recruitment of coactivators to enhance transcription
What causes primary hypothyroidism?
autoimmune of Hashimoto's thyroiditis
antibodies against TPO and Tg cause destruction of thyroid follicular cells (antibodies can be measured for clinical diagnosis)
iodine insufficiency in other countries
What is synthetic T3 hormone? Why is use not favored? AEs?
active thyroid hormone
much shorter half life, use results in concentrations of T3 in the blood above what typically would be present, lose the ability for on demand conversion in target tissues when needed
same as levothyroxine, but may occur more immediate
What transporter is responsible for iodine uptake from circulation? How do iodine levels change the transporter's expression?
Na/I symporter
low dietary iron levels increase NIS expression and stimulate iodine uptake
What are the main differences between T3 and T4?
T3 is the active form, shorter half life
T4 has more half life, more is produced by the body, less made if pt has iodine deficiency
What are some of the main physiological effects of thyroid hormones to our organ systems?
Critical for CNS development and GH
Increases basal metabolic rate, generates heat, carbohydrate metabolism, regulates cholesterol and triglyceride metabolism
increase HR, contractility and output, stimulates GI
Endemic: caused by iodine deficiency, most prevalent form worldwide but not in the western world
Cretinism: physical and mental deficits due to congenital thyroid hormone deficiency, caused by maternal iodine deficiency
What drug is synthetic T4? How does it work? What is important for absorption? AEs?
levothyroxine
Converted to T3 on demand in tissues when needed
absorption increased on empty stomach, inhibited by certain drugs (sucralfate, cholestyramine, iron, calcium, aluminum, certain soy)
AEs: palpitations, tachycardia, arrhythmias, nervousness, sweating, heat intolerance, fever, HA, insomnia, GI