This document discusses thyroid hormones and antithyroid drugs. It begins by classifying hormones into different categories including thyroid hormones. It then describes the thyroid gland, its location and composition. The two principal thyroid hormones, thyroxine and triiodothyronine, are discussed along with their roles in metabolism and organ functioning. The biosynthesis and metabolism of thyroid hormones is explained involving thyroid stimulating hormones. Different classes of antithyroid drugs are then outlined, including thiomides, aniline derivatives, polyhydric phenols, and ionic inhibitors, describing their mechanisms of action in inhibiting thyroid hormone synthesis.

1. Prof. Amol S. Dighe
Hormones: Thyroid and
antithyroidal agents

2.  Hormones are classified generally 1- thyroid hormones 2-
parathyroid hormones 3- pituitary hormones 4- Pancreatic
hormones 5- Adrenal gland hormones 6- Sex hormones
 Thyroid hormones –
 All vertebrates have thyroid glands.
 It is not essential for life but it is necessary for growth and mental well
being.
 In a healthy adult, it weight about 25 g and is composed of two lobes
which lie one on either side of the larynx.
 It is longer in women then in men.
 At the posterior surface of each thyroid gland, can be seen the parathyroid
gland.
 The hormone has molecular weight of about 680000 and it contains
organically bound iodine.
 A large quantity of iodine (0.06%) is present in thyroid gland, almost all of
which is firmly bound to protein largely in the form of the thyroid

3.  On hydrolysis , thyroglobulin is converted to several
iodinated tyroine derivatives.
 Thyroid hormones are part of thyroglobulin molecule which
is formed in the microsomes of the follicular cells.
 Thyroxine and tri-iodotyrosine are the principal thyroid
hormones.
 Chemically they are amino acid containing iodinated diphenyl
ethers.
 tri-iodotyrosine is more active then Thyroxine
 These hormones necessary for
 1- oxygen consumption, heat production and metabolism of carbohydrate,
fats and proteins
 2- proper functioning of gastrointestinal tract, cardiovascular, reproductive,
skeletal and neuromuscular system.
 3- optimal functioning of catecholamine, antidiuretic hormones.
 4- normal growth and differentiation.

5. Biosynthesis , storage and metabolism of
thyroid hormones.
 The biosynthesis of thyroid hormones is regulated by
variations in the plasma levels of thyroid stimulating
hormones (TSH) from the anterior pituitary gland.
 The conversion of inorganic iodide to thyroid hormones
involves following steps-
 1- iodine uptake by the gland
 2- oxidation of iodine and iodination of tyrosyl groups
 3- formation of thyroxine and tri-iodothyronine from iodotyrosines
 4- release of thyroxine and tri-iodothyronine.

7. SAR
 1- the two phenyl rings must be connected by an ether,
thioether or methylene linkage in order to maintain the
activity.
 2- a carboxyl group must be present in aliphatic side chain.
 3- halogen and methylene substituent's may be placed at 3
and 5 position.
 4- the 3 monosubstituted analogs are more active than the 3,
5 disubstituted compounds.
 5- for maximal activity, position 4 should be occupied by a
hydroxyl group

8. Antithyroid drugs
 These drug act by inhibition of the synthesis of thyroid
hormones.
 They exert immediate effects since they act at the first stage
of iodine incorporation by the gland.
 They are categorized as under
 1) Thiomides
 2) Aniline derivative
 3) polyhydric phenols
 4) ionic inhibitors that block the uptake of iodine by the gland
 5) Miscellaneous agents.
 1) Thiomides- thiourea and thiouracil derivative are among
the primary drugs to treat thyroid hyperactivity.

9.  The methyl and propylthiouracil are effective drug. Skin rashes
are the most common side effects of these drugs.

10. 2)Aniline derivative-
 These agents interfere with some of the processes catalyzed by thyroid
peroxidase like, iodide oxidation, organification and coupling of
iodotyrosines.

11.  3) Polyhydric Phenols-
 The only clinical agents from this category is resorcinol.
 4) Ionic inhibitors-
 These anions resemble iodide ions and affects the power of thyroid gland
to accumulate iodide.
 e.g. Potassium perchlorate, thiocyanate.
 5) miscellaneous agents-
 Lithium carbonate- lithium appears to prevent the release of both
hormonal and non-hormonal iodine from the thyroid gland.