Thyroid hormones

Thyroid hormones ( TH )

Maintain metabolism. ? normal growth and maturation.
Hypothyroidism
Bradycardia , cold resistance , mental and physical. retardation. and dwarfisim
Hyperthyroidism
Tachycardia and cardiac arrhythmias body wasting, nervousness, tremor & excess heat production.
TH
triiodothyronine -T3
thyroxine - T4
Calcitonin
Synthesis
TRH? TSH ? thyrotropin? TH(s)
Dopamine, somatostatin and glucocorticoids ? inhibit TSH secretion
TH(s) ? - TRH release
TSH? cAMP ? iodide(-I )---peroxidase --- iodine ( I2 ) ---iodination ? tyrosin on thyroglobulin. ?condensation. ? T3 and T4 ---- proteotic cleavage. ?TH release

Mechanism of action:
Thyroxine-binding globulin (plasma ) ?T3 ,T4 by diffusion. or active transport ? cells---deiodination ?T3 ?nucleus.
? activate receptor? RNA formation ? protein synthesis. ? T4 effects.
Kinetics
Orally ,food ,calcium and aluminum-containing antacids ---- T4
Phenytoin. , Rifampin , Phenobarbital.
Hypothyroidism. ? high TSH ----- Levothyroxin ( once ,steady state? 6-8 weeks )
Levothyroxin toxicity.

Hyperthyroidism .(thyrotoxicosis )-------Graves disease., Toxic adenoma , Goiter
TSH level

Treatment
131
1-surgical , I ----T4
2-Thioamides ( Propylthiouracil- PTU , Methimazole ) -----inhibit oxidation & coupling. ? inhibit thyroid hormones synthesis
In addition Propylthiouracil blocks conversion of T4 to T3
Thioamides have delayed clinical effect s?
Thioamides ---- absorption, t 1/2 , onset
Advers effects
agranulocytosis. , rash, edema





Tyrosines iodination. (Acute Wolff Chaikoff effect )
3-iodide{


Thyroid hormones release



Uses
Fatal thyrotoxic. Crisis ( thyroid strom )-
-Prior to surgery.

Iodide long term use
Iodide --- orally ? sore mouth and throat swelling tongue. or larynx., rash , mucous membranes ulceration and metallic taste
Thyroid strom
-Beta blockers with no sympathomimetic activity----propranolol ( I.V )
-Calcium channel blocker-----Diltiazem
-Iodide
-Glucocorticoids (shock )