Thyroid Flashcards
Where does T3/T4 synthesis occur?
Follicle cells of the thyroid
Steps of T3/T4 production
- Iodide –> iodine
- Incorp into tyrosine residues in thyroglobulin molecules
- DIT/MIT made
- Put DIT/MITs together –> T3/T4
- Endocytosis into colloid droplets
- Lysosomes act and release T3/T4
D1
Activates T4 -> T3
Liver, kidney, thyroid
D2
Activates T4 -> T3
fat, heart, skeletal muscle, CNS
D3
Inactivates T4 -> rT3
Placenta, skin, brain
What can inhibit D1 activity?
States: Illness, low calories, fetal period, selenium deficiency, lots of fatty acids
Drugs: glucocorticoids, B blockers, PTU, amiodorone
What cofactor is required for all deiodinases?
Selenium
Binding of thyroid hormones
99% bound in plasma
T4 more highly bound than T3
Mostly TBG, a little of albumin and TBPA
What causes and what can happen with an increase in binding proteins?
Cause: estrogen, methadone, pregnancy
Free levels would fall, TSH stim, more hormone produced, normal levels achieved
Factors that increase binding of T4 to TBG
Estrogen, methadone, 5FU, heroin, liver dz, HIV
HHELM5
Factors that decrease binding of T4 to TBG
Glucocorticoids, androgens, salicylate, antisezuire meds, illness
SAAIG
Compared to T4, T3 is…
More potent
Has higher affinity for Receptor
Shorter t 1/2
Where is T4 absorbed best?
Duodenum, ileum – modified by intraluminal factors (drugs, food, flora)
Which is more absorbed, T3 or T4?
T3 - minimally affected by intraluminal binding proteins
Effects of non-euthyroid states on pharmacokinetics
Hyperthyroidism: can inc clearance of T3/T4
Hypothyroidism: can dec clearance
Naturally occurring isomers are in which form
L isomer
Indications for thyroid replacement
Adult hypothyroid (Hashimoto) Infantile cretism (iodine def) Endemic goiter
Drug of choice for hypothyroid?
levothyroxin (T4)
AE of levothyroxin
Cardiac sx - angina and palpitations, caution in elderly
Issues with L-triiodothyronine (T3)
Rarely used
Short half life – take often
Expensive
Greater risk in cardiotoxicity
Liotrix
Biological ratio of T4:T3 (4:1)
Not necessary, body can convert
May be good for genetic polymorphism in deiodinase enzyme
Drug interactions with thyroid replacement therapy
Pregnancy (more), elderly (less) dose adjustment
Rifampin increases T4 clearance
Cholestyramine decreases GI absorption
Major drugs for thyrotoxicosis
Methimazole (MMI)
Propyltiouracil (PTU)
MMI/PTU mechanism
Inhibits TPO catalyze reactions to block iodide organification
Blocks coupling of iodotyrosines
PTU also blocks D1
Onset, duration of tx of MMI/PTU
Slow, takes 3-4 weeks to deplete hormone
Tx for 2 years, may have permanent remission
AE of MMI/PTU
Skin rash
Joint pain
Agranulocytosis
Hepatotoxic (PTU +)
Pregnancy and hyperthyroid tx
PTU first trimester and nursing mothers
Then switch to MMI (MMI greater birth defects)
What drug tx for thyroid storm
PTU
Anion inhibitors MOA and AE
MOA: blocks thyroid uptake in those with iodide induced hyperthyroidism (amiodorone)
AE: aplastic anemia
Iodides - use and MOA
with PTU and beta blocker in thyroid storm
MOA: Wolff Chaikoff effect to inhibit hormone release, decrease size of hyperplastic gland
AE of iodide
Uncommon and reversible
Rash, swollen salivary glands, mucus membrane
FETAL GOITER IN PREG
Pre-op tx for subtotal thyroidectomy
thioamide for 6 weeks until euthyroid
KI x 10 days to reduce size
B blocker for sx relief
Radioactive iodide (I-131)
Rapidly concentrates in thyroid follicle where B articles selectively destroy gland w/o injury to adjacent cells –> 6-8 weeks
No kids or preg
80% of pts become hypothyroid
