M2- lecture 15: thyroid disorders Flashcards
what hormones do the thyroid gland secrete?
thyroxine (t4)
tri-iodothyronine (t3)
calcitonin
what are t4 and t3 important for?
they are important for normal growth/ development and the control of energy metabolism.
whats the main steps in synthesis and storage of thyroid hormones ?
uptake of plasma iodide by the follicle cells
iodination of thyroglobulin
secretion of thyroid hormones
whats thyroperoxidase ?
it oxidizes iodine and incorporates iodine radicals into tyrosine residues of thyroglobulin
how are thyroid hormones regulates?
they are regulated by TRH and protirelin which causes the anterior pituitary to release TSH.
not the difference between TRH and TSH
what does TSH act on ?
acts on GPCR in thyroid follicle cells which increases cAMP and activates of PI3K.
what are the actions of TSH on thyroid cells and what type of actions are they?
TROPHIC ACTIONS
- increases NIS expression
- synthesis/secretion of thyroglobulin TG
- generation of H2O2 and iodination of tyrosine
- endocytosis/ proteolysis of TG
- secretion of t3 and t4
- increased blood flow through the gland.
what are the causes of hypothyroidism ?
- hashimoto’s disease (autoimmune disorder)
- leads to enlargement of the thyroid gland (goitre)
what are the symptoms of hypothyroidism?
- low metabolic rate, lethargy
- slow speech
- bradycardia
- sensitivity to cold
- myxedema (Severe cases)
what are some thyroid replacements for hypothyroidism?
T4 (most common)
t3 (more active)
whats the mechanism of action for thyroid replacements? the general mechanism of action.
- exogenously administered t4 is deiodinated to t3
- bind to intracellular nuclear thyroid hormone receptors (10x more affinity for t3 than t4).
whats the MOA related to T3? for hypothyroidism ?
t3 impacts numerous bodily systems:
- metabolism: increased body temp and reduced weight
- cardiovascular: increased HR and BP
- GI: increased motility.
- Musculoskeletal: required for skeletal development and peak bone mass.
- reproductive: enhance ovulation and spermatogenesis
what are 2 adverse effects for hypothyroidism?
tachycardia (contraindicated)
atrial fibrillation
what are some causes of hyperthyroidism? (thyrotoxicosis)
- diffuse toxic goitre (Graves’ Disease)
- toxic nodular goitre
what are some symptoms of hyperthyroidism?
- high basal metabolism (increased appetite associated with body weight loss)
- increased skin temp
- heat intolerance
- sweating
- nervousness and tremor
- tachycardia
when is surgery administered for hyperthyroidism?
used if mechanical problems occur like thyroid compressing the trachea.
whats one drug thats used to treat hyperthyroidism ?
radioiodine (131I)
- first line treatment for hyperthyroidism
- dose is generally 5-15 mCi
whats the MOA of radioiodine?
- its taken up and processed the same way as normal iodine by the thyroid
- isotope emits beta-particles that have a short range and cytotoxic actions within thyroid follicle cells.
- given as a single dose that makes at least 1 month to start mediating its actions.
what happens after radioiodine is administered?
- following use and destruction of the gland, individuals will become hypothyroid and require administration of T4
whats another drug thats used for hyperthyroidism?
Antithyroids (thioamides)
- propylthiouracil
- methimazole, carbimaxole (prodrug converted to methimazole)
whats the MOA of antithyroids (thioamide)?
contain a thiocarbamide (S-C-N) group required for antithyroid activity
- prevent synthesis of thyroid hormone
- inhibit thyroperoxidase
- block iodine oxidation
- block coupling of iodinated tyrosines
- inhibit peripheral deiodination of t4 to t3 (propylthiouracil)
- REQUIRES 3-4 WEEKS TO WORK
whats the contraindications for thioamides?
pregnancy
what are some AE of thioamides?
skin rash,
neutropenia
-agranulocytosis
what is antithyroid (Lugol Iodine)?
- solution of potassium iodide with iodine in water
- symptoms of thyrotoxicosis subside within 1-2 days
- used for either severe thyrotoxicosis or preparation for surgery .
whats the MOA of lugol iodine? (antithyroids)
- iodide in excess amounts inhibits thyroid hormone secretion
- reduces vascularity of the thyroid gland
- may also inhibit iodination of thyroglobulin by reducing generation of H202.
