3.5 Thyroid Flashcards
What hormone is released from the hypothalamus that eventually leads to thyroid hormone release? What kind of hormone is it?
Thyrotropin Releasing Hormone (TRH) is released from the hypothalamus (–> TSH release from anterior pituitary)
TRH is a tripeptide
What kind of receptor does TRH bind to to illicit TSH release?
TRH binds to GPCR –> IP3 –> Ca++ –> vesicular/membrane fusion and TSH release
TSH is composed of two chains (alpha and beta). Which chain is common to other pituitary hormones?
Alpha chain is common to TSH, LH, FSH, and hCG (placental hormone)
TSH is composed of two chains (alpha and beta). Which chain distinguishes TSH from other pituitary hormones?
Beta chain…significant for specific TSH events
What kind of receptor does TSH bind to?
TSH binds to a GPCR
What is the effect of TSH binding to its GPCR?
Secretion of mature thyroid hormones
Production of new thyroid hormone batch
What needs to be unregulated by TSH in order to synthesize more thyroid hormones?
Thyroid peroxidase synthesis
Thyroglobulin tsx
Na+/I+ symporter
There are ~7 steps to thyroid hormone synthesis. What is necessary to happen I in order for it to be used?
Iodide (I-) has to be oxidized to Iodine (I)
This is called organification
There are ~7 steps to thyroid hormone synthesis. What are the possible products of Iodine binding to tyrosine?
Monoiodothyronine (MIT)
Diiodothryonine (DIT)
There are ~7 steps to thyroid hormone synthesis. What happens after MIT and DIT are formed?
Conjugation of MIT/DIT or DIT/DIT occurs…forming T3 or T4 respectively
Which thyroid hormone, T3 or T4, has the shorter half-life?
T3 has the shorter half-life (~1 day)
Which thyroid hormone, T3 or T4, is more active?
T3 is more active…T4 can also bind to Thyroid Hormone Receptor, but it is often converted to T3
So basically, just short of all T3/T4 is circulating BOUND to a protein. Which proteins bind to thyroid hormones?
Thyroxine binding globulin (75% of each)
Transthyretin (20% T4; 5% T3)
Albumin (5%T4; 20% T3)
When are thyroid hormone binding proteins increased?
During pregnancy
What decreases thyroid hormone binding proteins?
Androgens
Hyperthyroidism
Malnutrition
Nephritic syndrome (causes protein loss)
Deiodinase I, II, and III all metabolize thyroid hormones to some extent. Which one is most prevalent in the liver and kidneys? What is the result of this enzymes activity?
Deiodinase I is primarily in the liver/kidneys
Deiodinase I converts T4 to either active T3 or inactive rT3
Deiodinase II is present in the brain, pituitary, skeletal and cardiac muscles. What are the results of its enzymatic activity?
Deiodinase II works with deiodinase I to convert T4 to active T3
I + II = active T3
Deiodinase III is present in the brain, skin, and placenta. What are the results of its enzymatic activity?
Deiodinase III works with deiodinase I to inactivate hormone…makes rT3
Where is the thyroid hormone receptor?
Pretty sure that TH binds to THR in the cytoplasm, enters the nucleus, and dimerizes with RXR
How does thyroid hormone enter a cell?
Either carrier-mediated transport (protein bound form?)
Diffusion (free form)
What are the main actions of thyroid hormone?
Regulation of BMR
Heat production
Glucose utilization, uptake, and synthesis
Permissive sympathetic effects (increase HR and contractility)
Why do most states mandate that all newborns get tested for thyroid function?
Because if hormone replacement is started early enough the child will grow/develop normally
What is cretinism?
Hypothyroid in infants
What are some signs of cretinism?
Profound mental/growth/motor/sexual retardation
Coarse hair
Protuberant abdomens
What are two potential causes of cretinism?
Congenital lack of thyroid hormone in infants
Maternal hypothyroidism
What can cause maternal hypothyroidism?
Lack of iodine in diet (rare)
Hashimoto’s thyroiditis (makes TSH receptor antibodies)
Exposure to radioactive iodine or antithyroid drugs during pregnancy
What are the symptoms of low thyroid hormone in adults?
Lethargy/somnolence
Slowed intellectual functions (including speech)
Stiffness/aching muscles
Cold intolerance
Delayed deep tendon reflex and relaxation
Menorrhagia and anovulation
Excess thyroid hormone in adults has a lot of down stream effects. What is a general rule to apply?
Excess thyroid hormone speeds things up (increased HR, increased bone resorption, increased GI motility, increased liver function…)
What is thyrotoxicosis? What is thyroid storm?
Thyrotoxicosis is any cause of excess thyroid hormone concentration
Thyroid storm is the extreme version of thyrotoxicosis
Knowing that excess thyroid hormone increases many basic functions, what drugs should be given to people with severe thyrotoxicosis?
Beta blockers (there are increased receptors) Thinamides (antithyroids) Corticosteroids (for functional hypoadrenalism)
What is the likelihood of a patient with severe thyrotoxicosis progresses to thyroid storm? What is the likelihood that a thyroid storm will end in death?
10% progress to thyroid storm
20-30% with thyroid storm die d/t disease
What are some causes of primary hypothyroidism?
Congenital defects
Gland destruction
Iodine deficiency
Hashimoto’s thyroiditis or chronic lymphocytic thyroiditis (autoimmune disorders)
What causes secondary hypothyroidism? Tertiary hypothyroidism?
Pituitary gland disorder causes secondary hypothyroidism
Hypothalamus disorder causes tertiary hypothyroidism
What is Graves’ disease?
Production of Thyroid Stimulating Immunoglobulins (TSIs)
If a Graves’ patient becomes pregnant, can the baby be effected by the TSIs?
Yes…IgG can cross the placental membranes
What is a goiter?
Enlarged thyroid gland
What can cause the formation of a goiter?
Hypo or hyperthyroidism
Iodine deficiency
How can Iodine deficiency cause a goiter?
Iodine deficiency → low T3/T4 → increased anterior pituitary production of TSH → thyroid gland enlarges
How can Graves’ disease cause a goiter?
Thyroid stimulating immunoglobulins activates thyroid gland enlargement regardless of the negative feedback
What are three diagnostic tests for thyroid function?
TSH test
T3 and T4 test
TSI test
What does a low TSH indicate? High TSH?
Low TSH –> hyperthyroidism
High TSH –> hypothyroidism
What does high T3 and T4 indicate?
Hyperthyroidism…self explanatory
When is the only time a TSI test is effective?
Graves’ disease
Levothyroxine is a T4 drug. How many times does it have to be taken per day? Is it safe? Does it have a long or short half-life?
Levothyroxine should be taken once daily…it is safe at that dose, but has a narrow TI
Levothyroxine’s half-life is 7 days…reaches steady state in 6-8 weeks
What dietary substances can decrease absorption of levothyroxine?
Iron, calcium, AlOH, and soy
What conditions require a smaller dose of levothyroxine? What conditions require a higher dose of levothyroxine?
Old age and cardiac disease require a decreased dose
Pregnancy requires a 30-50% higher dose
Liothyronine is a T3 drug. When would this drug be administered?
When quick onset is desirable
What are three kinds of thioamides (thionamides)?
Propylthioruacil (PTU)
Methimazole
KI
How does PTU work?
PTU inhibits deiodinase I and thyroid peroxidase
How does methimazole work?
Methimazole only inhibits thyroid peroxidase
Does PTU or methimazole have a longer duration of action?
Methimazole lasts 24hr…PTU only 12hr
How long does it take for methimazole or PTU to be effective?
2 weeks
What is a concern with PTU?
Liver injury
When can KI be used?
Prep for thyroidectomy
thyroid storm
Protection from radioactive iodine
How does KI work?
Basically, iodine flooding inhibits almost all aspects of iodine metabolism
What are some side effects to KI use?
Allergic RXN
Sore teeth/gums
Excess salivation
What is (131)Iodine used for?
Ablation of thyroid
What is (123)Iodine used for?
Imaging of thyroid
What hormones are negative regulators of thyroid hormone release?
Somatostatin
Dopamine
Glucocorticoids
