Thyroid Hormone &
Kinetics & dynamics of thyroid H.
Indications of thyroid H.
Toxicity of thyroid H.
Mechanism of actions
Uses & toxicity
Pharmacokinetics of thyroid hormones
Well absorbed orally except in
myxedema coma used by i.v.
It is distributed allover the body.
99.9 % is bound to thyroxine binding
Elimination of thyroid hormones
– 30-35 % of T4 T3 (5 times more potent than
– 45-50% of T4 reverse T3 (rT3) which is
– Further peripheral tissues deiodination, largely in
the liver, loss of activity.
Small amount of thyroxine is eliminated by
deamination, decarboxylation, or conjugation and
excretion as glucuronide or sulfate.
Dynamics of thyroid H.
Mechanism of action:
Thyroid hormones enter passively to
the cytoplasm, bind cytoplasmic
receptors, enter the nucleus, and bind
to DNA response element, increasing
RNA transcription and protein
Effects of thyroid hormones
Protein synthesis during growth.
Increased metabolic rate and oxygen
Increased sensitivity to catecholamine
with proliferation of beta receptors
(particularly important in the
Uses of thyroid hormones:
Replacement therapy: in hypothyroidism (critinism
* levothyroxine (T4) is used better than liothyronine
(T3) because it has a delayed onset & long duration
of action, T4 is converted to T3 in the body plus it
has a low cost, stability and easily monitoring of
Myxedema coma: use liothyronine (T3) 25 μg i.v/6h
* liothyronine is strong (5 times more active than
T4), rapidly acting & has a short duration of action.
Simple non toxic goiter: use T4 to suppress TSH.
TSH dependent cancer thyroid: use T4 to suppress
Gynecological disorders: amenorrhea & habitual
Hypercholesterolemia: (thyroxine increases the
metabolism of cholesterol to bile acid).
*use d-thyroxine in euthyroid or cardiac patients.
Toxicity of thyroxine
It is similar to hyperthyroidism
Increased basal metabolic rate BMR,
heat production, hyperpyrexia,
warmness, flushes, and intolerance to
increase of HR, cardiac work & output,
angina, arrhythmia, hypertension and
Thionamides (Thiourea derivatives)
carbimazole, methimazole & propylthiouracil
Well absorbed orally, distributed allover the body,
concentrated in the thyroid gland, pass BBB & placental
Carbimazole is a pro-drug converted in the liver to its active
Excreted in urine and milk causing critinism of the suckling
Mechanism of action:
Inhibit oxidation of iodide ions to iodine.
Iodide peroxidase iodine
Inhibit organification of iodine
Ioddine + tyrosine iodotyrosines
Inhibit coupling of iodotyrosines.
MIT + DIT T3
Propylthiouracil also inhibits the peripheral
conversion of T4 to T3.
Inhibit thyroid function after 2-4 weeks
(until depletion of the stored thyroxine in
Increase TSH, so increasing the size and
vascularity of the thyroid gland (goiter).
Increase release of exophthalmos producing
agent which aggravates exophthalmos.
Mild hyperthyroidism (total therapy 12-18 months
Temporary control of moderate & severe
hyperthyroidism until preparing the patient for
Temporary use of thionamides until the effect of
the radioactive iodine (131I) takes place (3months).
Propylthiouracil is preferred in thyroid storm and for
ladies during breast feeding of the baby as little
passes into milk.
Preparing the patient for
Thionamide (6 weeks to be euthyroid).
Potassium iodide (2 weeks) to
decrease the size & vascularity of the
gland prior to surgery.
Treatment of thyroid
Thyroid storm is a life-threatening emergency due to liberation of
huge amounts of the hormone
Propranolol slowly i.v 1-2 mg or 40-80 mg orally/6h. If
propranolol is contraindicated use diltiazem 90-120 mg orally
Propylthiouracil 300-400 mg/4h then give sodium iodide 1.0 g
i.v/24h or potassium iodide orally 10 drops/day to retard the
release of thyroid hormones.
Dexamethasone 2 mg/h or hydrocortisone i.v 50 mg /6h. to
prevent shock, inhibits conversion of T4 to T3 and decrease
the release of thyroid hormones.
Chlorpromazine for mental disturbance,
Aspirin and cooling for hyperthermia,
Treatment of CHF as usual.
Use the smallest possible dose of carbimazole or methimazole
because they pass the placenta causing fetal goiter.
In the 2nd trimester, surgery is preferred to the continued
During breast feeding:
Use propylthiouracil because it is little passing into the breast
Rash, fever, agranulocytosis, increase size and vascularity of
the gland, liver & kidney damage, SLE, loss of hair
pigmentation & critinism in baby.
Lugol's solution (5 % iodine + 10 % potassium iodide) orally
0.3 ml tid.
Potassium iodide orally 60 mg tid.
Mechanism of action:
Attenuate the effect of TSH on the thyroid gland, so decrease
the size & vascularity.
Decrease exocytosis and proteolysis of thyroglobulin.
Decrease release of T4 & T3.
The antithyroid effect is of rapid onset 1-2 days and
maintained for 10-15 days
Cannot be used for long time therapy because of relapse of
hyperthyroidism due to increased TSH (paradoxical effect of
Preoperative to decrease size and vascularity of the
overdoses of iodine may cause iodism (metallic
taste, excessive salivation, with painful salivary
gland, diarrhea, productive cough, running eyes &
nose, sore throat and rashes mimic chicken-pox).
It is treated by fluids (saline) and diuretics.
iodine therapy maximizes iodine stores in the
thyroid. This effect delays the response to
Iodinated Radiocontrast media (ipodate):
It is rapidly reducing T3 concentration in
It inhibits conversion of T4 to T3.
It also decreases the release of T4 from the gland
The beta radiations of 131I destroy thyroid
parenchyma, so decreasing hormonal release.
Easy administration (orally).
It is not expensive.
Suitable for old ages and cardiac patients
with moderate to severe hyperthyroidism and
unfit to surgery.
As with iodine therapy, overdoses may cause iodism.
overdose is treated by large dose of sodium or
potassium iodide to compete with the radioiodine
uptake by the gland, and then hasten excretion by
fluids and diuretics.
Local pain & congestion at the site of the gland.
Malignant changes in the thyroid after many years
Contraindications: pregnancy, children and
B-blockers decrease the supersensitivity of the
tissues to catecholamines in hyperthyroidism.
B-blockers don’t block all the metabolic effects of
the hormone, so not used alone except in mild
thyrotoxicosis in preparation for radioiodine
The chosen B-blockers should be non-selective
and without intrinsic sympathetic activity e.g.
propranolol & timolol