Flashcards in Lecture 100 thyroid physiology Deck (14):
Discuss the synthesis and secretion of thyroid hormones, as well as how the
hormones are carried in the serum and how they are metabolized in the tissues.
short answer: begins with tyrosine residues and throglobulin protein being complexed with iodine and ends with release of T4 (mostly) and T3 in blood stream.
1. Synthesis of a large protein called thyroglobulin in thyroid epithelial cells.
2. Active transport of iodide (I-) into the thyroid epithelial cell. (via Na/I cotransporter, powered by Na/K pump)
3. Iodination and coupling of tyrosyl residues in thyroglobulin (TG) to yield T3 and T4. This occurs at apical membrane cia thyroid peroxidase (oxidizes iodide and couples iodide to tyrosine and tyrosine to tyrosine). Iodide is transported here by pendrin. the end product is then stored as colloid (iodinated thyroglobulin) in follicles
4. Endocytosis (by follicule epithelial cells) and proteolysis (by lysosome fusion) of TG, releasing T3 and T4.
Discuss the feedback mechanisms between thyroid, pituitary and hypothalamus that regulate thyroid hormone production.
negative feedback: T3 is produced in plasma or pituitary by type 2 deiodinase (note normally T3 is made from T4 in tissues), T3 inhibits TRH
positive feedback: TSH production from pituitary increased by TRH for hypothalamus
Describe the interaction of thyroid hormone with its receptor and how thyroid hormone actions are carried out.
T3/T4 are carried in blood bound to thyroxine binding globulin, T4 enters tissues by diffusion or by facilitated transport where it deiodinase converts it to T3. T3 interacts with its receptor (TR) in the nucleus which causes it to make a heterodimer with RXR to interact with the thyroid response element (TRE) and create thyroid hormone responsive genes
List the tissues whose function is modulated by thyroid hormone, and describe in what fashion important tissue functions are modified by thyroid hormone.
-fetal brain and skeletal development, generation of heat (i.e brown adipose tissue metabolism in infants),
-sympathetic nervous system (increase beta-adrenergic receptors/increases catecholamine production),
-increase in cardiac inotropic and chronotropic function (increase myosin heavy chain alpha=more contractility vs myosin heavy chain beta;increase in Ca ATP production, increase beta-adrenergic receptors),
-liver (increase hepatic gluconeogenesis/glycogenolysis)
-GI increase absorption of glucose
-endocrine- increased cholesterol degradation, increased lipolysis (to generate glucose for more metabolically active tissues)
Describe the consequences of inadequate or excess thyroid hormone in adults. name a cause
-excessive in adults-hyperthyroidism, rapid heartbeat, hand tremor, anxiety, sweating, weight loss, hunger, oily skin, frequent bowel movements, and difficulty sleeping. PE-rapid pulse, damp skin, hand tremor, eyelids retracted, enlarged thyroid.
-infrequent in adults-hypothyroidism, fatigue, mild weight gain, constipation, cold intolerance, difficulty thinking clearly. PE-fatigued appearance, dry skin, coarse hair, puffiness around the eyes, delayed reflexes.
excess-thyroiditis, toxic or hyperfunctioning nodule(s), grave's disease
what is Wolff-Chaikoff effect? was it it causes by? is it effective to take KI everyday?
Saturation of the thyroid gland with iodine leads to the Wolff- Chaikoff effect, where organification is inhibited. seen in patients who receive iodinated IV contrast for CAT scans or cardiac catherization. It would not be useful to take KI every day because the Wolff-Chaikoff effect is transient (peaking in about 10 days), and eventually a normal thyroid gland can “escape” the Wolff-Chaikoff effect and begin organification again.
which is more potent T3 or T4? what is benefit of PTU over other drugs?
T3 is a more potent thyroid hormone than T4. A small amount of T3 is produced directly by the thyroid gland, but the majority of it is produced by T4 to T3 conversion in the tissues. PTU’s ability to decrease T4 to T3 conversion, means levels of T3 are reduced, thus decreasing symptoms and complications of hyperthyroidism more rapidly.
A 25 year-old woman is referred to you two weeks after surgery for a 3 cm thyroid cancer. Her entire thyroid gland has been removed. She is on no medications, including no thyroid hormone supplements. Based on what you know about thyroid physiology, what do you think her TSH value is now (normal, low or high)? After surgery has been performed, the standard treatment for her cancer is with a single oral dose of radioactive iodine. On the day of the radioactive iodine treatment, is it best for the TSH to be normal, low or high? Once her treatment is complete and you are observing her over time, is it best for the TSH to be normal, low or high?
After the entire thyroid gland has been removed there is no source for thyroid hormone in the body. The lack of thyroid hormone would stimulate the hypothalamus to produce TRH and the pituitary to produce TSH, so the TSH would be high. It is best for the TSH to be high on the day of radioactive iodine therapy because that will better stimulate any remaining thyroid cancer cells to take up the radioactive iodine, thus increasing the likelihood they will be killed. Long-term it is usually best to keep the TSH below normal in thyroid cancer patients by giving them a higher daily dose of thyroid hormone. TSH is a growth factor for the thyroid (and thyroid cancer), so keeping the TSH level low decreases the chances the cancer will recur.
Describe the consequences of inadequate thyroid hormone in children. name some causes
listless behavior Growth abnormalities of the skeleton and mental retardation are typical findings. congenital absence of thyroid
what does T3 and T4 stand for? how are they different structurally? what animo acids precursor do they stem from, what other hormones share this precursor?
T4 has an extra I on the 5' position (outer carbon ring)
tyrosine-steroid hormones also come from this
What time of membrane protein is thyroid peroxidase? what enzyme does it resemble?
MPO-like (myeloperoxidase like)
region has high homology to the myeloperoxidase in neutrophils
name three ways thyroid is regulated
– The hypothalamus and pituitary feedback loops
– Deiodinases that metabolize thyroid hormone
– Autoregulation of the thyroid’s function in response to iodine supply
what are diodinases? what are the three types?
enzymes that convert T4 to T3 or reverse T3, controls thyroid hormone activity by changing its potency
I-liver kidney, muscle, thyroid (T4-plasma T3)
II-brain, pituitary, brown fat, placenta (T4 to intracellular T3)
III-placenta, brain, skin, fetal liver (inactivates T4 and T3)