Thyroid hormone and antithyroid drugs
Thyroid hormone
The thyroid hormones include thyroxin（T4）and triiodothyronine（T3）. They are
essential for normal growth and development and play an important role in energy
metabolism.
Synthesis, storage and release of thyroid hormones
The thyroid hormones are synthesized and stored as amino acid residues of
thyroglobulin, a protein constituting the vast majority of the thyroid follicular colloid.
The major step in the synthesis, storage and release of thyroid hormones are the
following :
 The uptake of iodine ion by the thyroid gland
 The oxidation of iodine and the iodination of tyrosyl groups of thyroglobulin
（production of MIT and DIT）: the oxidation of iodine to its active form is
accomplished by thyroid peroxidase
 Formation of thyroxin and triiodothyronine from iodotyrosines
the
remaining synthetic step is the coupling of two diiodotyrosyl residues to form
thyroxin or of monoiodotyrosyl and diiodotyrosyl residues to form triiodothyronine,
these steps are also catalyzed by the same peroxidase discussed above.
 Secretion of thyroid hormones since thyroxin and T3 are synthesized and
stored within thyroglobulin , proteolysis is an important part of the secretory process.
This process need an enzyme called thyroglobulin hydrolase.
 The conversion of thyroxine to triiodothyronine in peripheral tissues as well
as in the thyroid
 The regulation of thyroid hormones Controlled by HPT axis feedback
mechanism
TRH
TSH
T3, T4
Serum concentratins of thyroid hormones are precisely regulated by a negative
feedback system. TRH（thyrotropin-releasing hormone）released by hypothalamic
cells stimulate the synthesis of TSH （thyrotropin or thyroid stimulating hormone）
by the thyrotroph, and TSH in turn stimulate the thyroid to secrete more hormones.
These thyroid hormones, in a classic negative feedback fashion, decrease the
synthesis and secretion of TRH and TSH.
Action of thyroid hormones
 Growth and development:thyroid hormones is essential for normal
development of human being , especially in the central nervous system. the absence of
thyroid hormone lead to irreversible mental retardation（cretinism）
 Calorigenic effects:T3 /T4 can increase oxygen consumption, promote
metabolism and BMR（basal metabolic rate）.
 sensitivity to catecholamine
Cardiovascular effects: Tachycardia, hypertension
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nervous Effects: anxiety, nervous.
Pharmacokinetics the effects of T3 is much stronger and faster than T4.
Clinical uses the major indications for the therapeutic use of thyroid hormones
are for hormone replacement therapy in patients with hypothyroidism or cretinism .
 Cretinism Success in the treatment of cretinism depends on the age at
which therapy is started. The earlier, the better.
 Myxedema adult hypothyroidism, is the most common disorder of thyroid
function.
 Simple goiter the disease is prevalent because dietary iodine is not
sufficient. Through the negative feedback system, TSH is secreted in excess and the
thyroid gland becomes hyperplastic and hypertrophies.
Antithyroid drugs
These drugs are used to treat hyperthyroidism. To these patients, the T3/T4 level in
their blood are much higher than normal. The term hyperthyroidism is restricted to
those conditions in which thyroid hormone production and release are increased due
to gland hyperfunction. A large number of compounds are capable of interfering
directly or indirectly with the synthesis, release or action of thyroid hormones. The
major inhibitors may be divided into four categories:
Ⅰ Thioureas which interfere directly with the synthesis of thyroid hormones
Ⅱ High concentrations of iodine itself which decrease the release of
thyroid hormones
Ⅲ Radioactive iodine which damage the gland with ionizing radiation
Ⅳ β-adrenergic receptor antagonists which is useful in controlling the
peripheral manifestations of thyrotoxicosis, they have no specific effects on thyroid
gland and belong to adjuvant therapy.
Ⅰ Thioureas
these drugs can be divide into two categories according to thier
structure:
Thiouracils: methythiouracil , propylthiouracil
Imidazoles: methimazole , carbimazole.
 Pharmacological action and Mechanism of action These drugs inhibit the
peroxidase enzyme, the key enzyme in the production of thyroid hormones, thus
inhibit the synthesis of thyroid hormones. They inhibit the formation of thyroid
hormones by inhibiting the oxidation of iodine ion and the coupling of iodotyrosyl
residues to form T3/T4.
 Therapeutic uses
 As definitive treatment to control hyperthyroidism
 Preoperative preparations for subtotal thyroidectomy. to reduce the
operative morbidity and mortality, patients must be rendered euthyroid prior to
subtotal thyroidectomy as definitive treatment for hyperthyroidism. Prior treatment
which usually is successful in rendering the patients euthyroid for surgery. Iodine is
added to regimen for 7 to 10 days prior to surgery to decrease the vascularity of the
gland, making it less friable and decreasing the difficulties for the surgery.
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 Untoward reactions The most serious reaction is agranulocytosis. It is
reversible upon discontinuation of the offending drugs. The most common reaction is
a mild, occasionally purpuric, urticarial papular rash.
Ⅱ Iodine and iodide
 Pharmacological effects
 in small dose, it can stimulate the synthesis of thyroid hormones
 in large dose , inhibit the release of thyroid hormones into the circulation.
It can also mildly decrease the synthesis of thyroid hormones. High plasma iodide
concentration is an inhibition of the release of thyroid hormone. The changes include:
vascularity is reduced, the gland becomes much firmer and smaller.
 Therapeutic uses
 Simple goiter in small dose
 In preparation for thyroidectomy In large dose. Prior to surgery, iodine is
sometimes employed alone, but more frequently it is used after the hyperthyroidism
has been controlled by thioureas, it is then given for 7 to 10 days immediately
preceding the operation.
 Thyrotoxic crisis often in conjunction with thioureas and propranolol.
 Untoward reactions
 Acute allergic reaction which include angioneurotic edema and larynx
edema.
 Chronic iodism
 Thryoid dysfunction
Ⅲ Radioactive iodine
131
I was the most common used isotope of iodine. It has a half-live of 8 days. Its
radioactive emissions include both γrays（1%） and βparticles（99%）.
 Effects on the thyroid gland
131
I is rapidly and efficiently trapped by the thyroid gland and incorporated into
the iodoamino acids and deposited in the colloid of the follicles from which it is
slowly liberated. Thus the destructiveβparticles originate within the follicle and act
almost exclusively on th parenchymal cells of the thyroid gland. With little or no
damage to surrounding tissues. Theγrays passes through the tissue and can be
quantified by external detection.
 Therapeutic uses
 hyperthyroidism
Radioactive iodine is mainly used to treat
131
hyperthyroidism.
I is administrated orally and the effective dose differs for
individual patients. Lower-dosage 131I therapy has been advocated to reduce the
incidence of subsequent hypothyroidism. The clearest indication for this form of
treatment is hyperthyroidism in older patients and in those with heart disease., it is
also the best form of treatment when Graves’disease has persisted or recurred after
subtotal thyroidectomy and when prolonged treatment with antithyroid drugs has not
led to remission.
 diagnosis of thyroid functions
 Adverse reactions and contradications the chief disadvantage of the use of
radioactive iodine is the high incidence if delayed hypothyroidism . the main
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contradictions for the use of 131I therapy is pregnancy and young patients.
Ⅳ β-adrenergic receptor antagonists（adjuvant therapy）
β-R blockers are effective in antagonizing the catecholaminegic effects of
thyrotoxicosis by reducing the tachycardia, tremor and stare and relieving
palpitations ,anxiety and tension.
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