Download Thyroid Hormones

Thyroid Hormones
Thyroid Gland:
– Highly vascular flat structure.
– Located at the upper portion of the trachea.
– Composed of twp lobes joined by an isthmus.
Hormones of the Thyroid gland:
Thyroxin and triiodothyronin
Calcitonin
Thyroxin and Tiiodothyronin
■ Structures: Derived from single amino acid.
I
HO
I
NH2
CH2CH COOH
O
I
I
Thyroxine
I
5'
HO
NH2
CH2CH COOH
O
I
I
Triiodothyronine
Regulation:
Hypothalamus
Thyrotropine Releasing Hormone
(TRH)
Anterior Pituitary
Thyroid Stimulating Hormone
(TSH)
Thyroid gland
Thyroxin & Triiodothyronin
Biosynthesis
Iodine actively transported to the thyroid gland under
the influence of TSH.
Thyroid Peroxidase Enzyme (TPO) convert Iodine to
Hypoiodate (HOI).
TPO catalyze coupling of I - with tyrosine.
Thyroxin stored as Thyroglobulin.
TSH enhances lysosomes to release Thyroxin from
Thyroglobulin.
5’-Deiodinase convert Thyroxin to Triiodothyronin
mainly in the peripheral tissues (80%).
Structure Activity Relation Ship:
Angle between the two aromatic rings must be 1200.
3’-Monosubstituted molecules are more active than
3’, 5’-disubstituted ones.
Triiodothyronin is 4 times more active than Thyroxin.
3’-Isopropyl derivative is 7 times more active than
Thyroxin.
Transportation:
– Thyroxin bind to plasma protein.
– The main binding protein is called
“Thyroxin-binding globulin”.
Half life: 6- 7 days.
Actions of the Thyroid Hormones:
Enhance growth and protein synthesis.
Essential for the development of the nervous system.
Increase oxygen consumption and basal metabolic rate.
Increase body temperature “Calorigenic effect”.
Cardiovascular effect:
Increase heart rate.
Increase force of contraction.
Increase cardiac output.
Disease Due to Hypothyroidism:
Goiter:
Causes: Lack of iodine in diet.
Symptoms:
Enlargement in the thyroid gland (Thyroid Hypertrophy).
Low level of thyroxin.
High level of TSH.
Treatment: Iodine.
Cretinism:
Irreversible condition due to deficiency of thyroxin soon after birth.
Retardation in Physical and Mental development.
Myxedema:
Deficiency of thyroxin in adults due to:
Removal of thyroid gland by surgery.
Destruction of the gland by Radioactive Iodine.
Atrophy of the thyroid gland.
Symptoms:
Muscle weakness.
Poor appetite.
Slow heart rate and low cardiac output.
Dry cold skin and thick brittle nails.
Brittle coarse hair.
Puffy expressionless face.
Treatment:
Thyroxin for life.
Disease Due to Hyperthyroidism:
Graves’ disease (Diffuse Toxic Goiter):
Causes: Autoimmune disease resulted in Enlargement
and excessive secretion of the thyroid gland.
Symptoms:
Enlargement in the thyroid gland (Thyroid Hypertrophy).
Protrusion of the eye balls.
High body temperature and flushes.
Thyroid cancer:
Treatment:
Antithyroid drugs.
Natural Thyroid Preparations:
Thyroid USP:
Deffated bovine or procine thyroid gland.
Proloid:
Partially purified thyroglobulin.
Desicated Thyroid Preparation:
Powdered acetone extract of bovine or procine thyroid
glands.
Synthetic Thyroid Hormones:
Levothyroxin T4:
Slow onset of action but long duration.
Liothyronin T3:
Rapid onset of action but short duration.
Liotrix:
4 : 1 mixture of T4 and T3.
Antithyroid Drugs:
Iodine:
Decrease vascularity of the gland.
Inhibits the release of thyroxin from thyroglobulin.
Side effects:
Hypersensitivity.
Enlargement of the thyroid gland on prolonged use.
Radioactive Iodine:
Calculated amount to destroy part of the thyroid gland.
Alternative to surgery.
Thionamides:
Inhibit TPO essential for thyroxin biosynthesis.
PTU (6-N-Propyl-2-thiouracil and Methimazole.
Hormones Affecting calcification
Calcium in the body:
Fifth most abundant element in the body.
A 70 kg adult contain approximately 1 kg of calcium.
99% of calcium is located in the bones.
The remaining 1% present in cells and plasma.
Calcium in plasma:
50% bound to proteins.
46% complexes with counter ions.
4% free ions. This fraction regulated by hormones.
Daily Requirements:
Ranging from 400 mg in infants to 1200 mg in pregnant and
lactating women.
Absorption and Excretion:
About 1/3 of the ingested calcium is absorbed through the
intestine.
Calcium absorption increased by:
Vit D.
PTH.
Calcium absorption decreased by:
Glucocorticoids.
Physilogical functions:
Increase neuromuscular excitability.
Important for contraction of vascular and other smooth muscles.
Essential for excitation and contraction of cardiac muscles.
Essential for bone growth.
Important for maintaining mucosal and cell membranes.
Involved in blood coagulation.
Calcitonin
Site of Secretion: Thyroid gland.
Structures:
Peptide Hormones composed of 32 amino acid in single chain.
Regulations:
By calcium ion concentration:
When calcium ion concentration in plasma increase calcitonin
concentration increase and Vic versa.
Physiological Functions:
Hypocalcimic effect.
Stimulate bone formation.
Direct inhibition of bone resorption.
Uses:
Hypercalcimia involving removal of calcium from
bones as in Paget’s disease.
Parathyroid Hormone (PTH)
Site of Secretion:
Parathyroid gland.
Structure:
Peptide Hormones composed of 84 amino acid in single chain.
Regulation:
By calcium ion concentration:
When calcium ion concentration in plasma decrease
PTH concentration increase and Vic versa.
Physiological Functions:
Hypercalcimic effect.
Stimulate mobilization of calcium from bones.
Increase GIT absorption.
Decrease calcium excretion and enhance
reabsorption.
Decrease calcium concentration in milk and saliva.
Calcimimetic Drugs
These drugs are used to control PTH concentration in patients
with secondary Hyperthyroidism or Parathyroid carcinoma.
These drugs increase the sensitivity of Parathyroid gland to
calcium. As a result the gland decrease PTH secretion.
E.g. Cinacalcet HCl “Sensipar”.