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what does thyroid dysfunction do to anti-depessants?
Renders them ineffective
synthesiszed in hypothalamus, travels to anterior pituitary using portal system.
Binds to TRH receptors on anterior pituitary (GPCR)
released by anterior pituitary into general circulation when TRH binds to TRH receptors
large pituitary glycoprotein (28kDa) composed of alpha and beta strands
Regulation of TRH and TSH
Thyroid hormones negatively regulate TRH secretion and TRH receptors levels in the ant. pituitary
Thryroid hormones also inhibit TSH production by inhibing TSH beta genes (transcriptional regulation)
TRH increased during sleep and decreased during non-specific stress
Amino acid precursor to thyroid hormones?
Tyrosine(also makes catecholamines)
How can perchlorates and thiocyanates affect iodine levels?
Block theuptake of iodide into the thyroid
What does thyroidal peroxidase do?
Oxidizes iodide into iodide closer to the apical side of the follicular cell.
What kind of staining shows the characterisitc pink colour of the acini?
Eosin staining, due to iodinated thyroglobulin
Where are T3/T4 made?
Following stimulation, thyroglobulin gets reabsorbed by endocytosis, and ishydroyzed by lysosomal enzymes to make T3 or T4, these get released into the blood.
Difference between T4 and T3
- T3 is 4-10X more active than T4
- T4 is the major product (>90%)
35% of peripheral T4 is converted to T3 by type I5-deiodinase
What do propylthiouracil and methimazole do?
Which proteins do thyroid hormones bind to?
What are some properties of free TH?
- Thyroxine binding globulin (75% of TH)
- thyroxine binding prealbumin
- serum albumin
(highest avidity to lowest)
- Only free TH is biologically active, but also readily degraded,
- only 0.05% of TH is free, 0.3% of T3 (In picomolar range)
How can aspirin and dicumarol affect TH?
Affect binding of TH to their carriers (thus decreasing half-life of hormones)
Catabolism of TH
Deiodination, followed by glucoronidation of the rest of the molecule.
What can affect TBG levels?
- Increase: estrogen/contraceptives/pregnancy
- Decrease: nuclear receptor type drugs like steroids, androgens, glucocorticoids
Affects of TH
- stimulation of protein synthesis (skeletal)
- increases O2 consumption, and increases basal metabolism
- Important for neural development (e.g. cretinism)
Also helps with phosphorylation; less effective ATP utilization, greater heat production without TH
Also impacts Cardiac output, BP, gastric motility, O2 consumption by muscles (muscular weakness in hyperthyroid)
Increased sensitiivty of tisues to catecholamines (increasing lipolysis, glycogenolysis, gluconeogenesis)
What is myxedema?
excessive Connective deposition (symptom in Grave's disease)
What is the mechanism for Grave's disease?
HLA-D IgG auto-antibodies stimulates TSH receptors (antibodies have long-half-lives, thus continual stimulation)
What are some treatments for hyperthyroidism?
Propylthiouracil/methimazole (Methimazole if patient isn't pregnant, can cause aplasia cutis in fetus) (both also have hepatotoxicity)
- Radioactive iodine
- High caloric/protein diet
- Ionic inhibitors like thiocyanate and perchlorate (no longer used )
propanolol for CV symptoms
What is thyroid storm
Acute,life-threatining, thyroid hormone induced hypermetabolic state. Common clinical presentation includes fever,tachycardia, neurologic abnormalities, hypertension, followed by hypotension
What are some differences between propylthiouracil and methimazole
- Both cause hepatotoxicity
- PTU=fulminant hepatitis
- Meth= Cholestatic jaundice
methimazole can cause aplasia cutis in fetus
PTU inhibits peripheral conversion of T4->T3, meth does not
Meth more potent than PTU, but does not inhibit peripheral conversion
Treatments for hypothyroidism
- Thyroxine treatment for life
- iodized salt
What are the most common antibody's in Hashimoto's?
- Thyroid peroxidase antibody (MOST COMMON)
- TSH receptor blocking antibody
- thyroglobulin antibody
- (The first two are more common)