Thyroid Disorders and

its treatment (hormone

analogues and their
inhibitors)

Dr. Nilay Solanki

Ramanbhai Patel College of Pharmacy
Charotar University of Science and Technology
 Thyroid gland (TG) –
Hypothalamus
single layer of
epithelium and filled + TRH
with Collid
Main Steps: Anteriod pituitary

Synthesis, Uptake of plasma + TSH

Storage, iodide by the follicle
Metabolism cells
and Oxidation of iodide and
Secretion of Iodination of tyrosine
T3 T4
residues
Thyroid of thyroglobulin
Hormones Secretion of thyroid
 T3 (10%) and T4 (90 %) are
retrieved from tyrosyl
residues of the protein
hormone thyroglobulin
 Iodide Transport
mechanism – energy Thyroid Follicle epithelial cell
dependent process
I-
I- I- I2
C
DIT
Thyroglobulin TG MIT MIT
NA-I
(TG)
symporter
TG is a protein - large TG
numbers of tyrosine
Regulation of MIT
amino acids – which
Iodination and
DIT
MIT DIT

Thyroid DIT
become thyroid
hormone molecules Coupling
Function T4 T4
MIT
Help of
Thyroperoxidase
T4
T4 T3 T4
T4 MIT
T4 TG
Lisosomal
degradation T4 TG
Plasma T3 DIT
T4
T3 DIT

Thyroid Follicle epithelial cell Follicle lumen

MIT, monoiodotyrosine
DIT, Di-iodotyrosine
 Types of Thyroid Disease

Hypothyroidism: Insufficient thyroid hormone production, common

cause of hypothyroidism is Hashimoto's thyroiditis

Hypethyroidism: Gland produces excessive amounts of thyroid

hormones, common cause is Graves' disease

Thyroiditis: Autoimmune – Hashimoto’s thyroiditis, Post-partum

thyroiditis

Emergency: Thyroid Storm, Myxedema Coma

 Pathophysiology of Hyperthyroidism
Loss of normal regulatory control of thyroid hormone (TH) secretion

Stimulatory action of TH on body leads to hypermetabolism

Rise in Sympathetic nervous system activity

Alteration of secretion and metabolism of Hypothlamic, pituitary and gonadal hormones

Excess amount of TH stimulate cardiac system and increased adrenergic receptor

Cardiac
effects Tachycardia, Increased cardiac output, stroke volume, adrenergic responsiveness and
peripheral blood flow

Negative Nitrogen balance, lipid depletion and Nutritioan deficiency

Hyperthyroidism
 PathophysiologyofofHypothyroidism
Pathophysiology Hypothyroidism

Due to Hashimoto's thyroiditis, lymphocytic infiltration of the

thyroid and germinal center formation,

Atrophy of the thyroid follicles accompanied by

absence of colloid, and mild to moderate fibrosis

Atrophic thyroiditis, the fibrosis is much more extensive, lymphocyte

infiltration is less pronounced

Hypothyroidism
 Pharmacological Actions of Thyroid Hormones (T3 & T4)
 T3 and T4 act on almost every cell of the body. Growth related actions linked with
increase the basal metabolic rate, protein synthesis, regulate long bone growth
Growth and (coordination with growth hormone) and neural system maturation, and increase the
Development body's sensitivity to catecholamines.

 Lipid Metabolism: T3 and T4 enhances Lipolysis by potentiating Catecholamines

and other lipolytic hormones

By suppressing Phosphodiesterase Which increases cAMP

Plasma free fatty acid levels are elevated

Metabolism  Carbohydrate Metabolism: Utilization of sugar by tissue is increased,

Glycogenolysis and Gluconeogenesis in liver; faster absoption of glucose from
intestines

 Protein Metabolism: Synthesis of protein increased, prolonged action resulted in

negative nitrogen balance and tissue wasting. In Hyperthyroidism main feature is
weight loss
  T3 and T4 increase BMR by stimulating Cell metabolism and reset of energystat.
 Imp for maintaining body temperature
Calorigenesis
 Mechanism – Uncoupling of oxidative phosphorylation (excess energy released as
heat)
 Heart rate, contractility and output is increased
CVS effect  T3 & T4 stimulate heart by directly acting on contractile elements (increasing
the myosin activity with greater Ca2+ ATPase activity) and by up regulation of β
receptor

 Profound functional effect of CNS

Nervous  Mental retardation is observed in Cretinism
system
 Behavioral feature are seen in Myxoedema
 Hypethyroid persons are Anxious, nervous, excitable
GIT and  Effect on gut is increased by T3 & T4
Kidney  T3 & T4 do not cause diuresis in euthyroid individual, flow of urine can be
effects enhanced when myxoedema patient treated with drugs.

 T3 & T4 has indirect action on reproduction.

Reproduction  Fertility is impaired in Hypo and women suffer from oligomenorrhoea.
 Normal fucntion is must for maintaining pregnancy and lactation
MECHANISMS OF ACTION OF THYROID
HORMONES
Genomic
action
Thyroid Hormone (T4, T3)
binds to Nuclear receptor
Target Cell
Cytoplasm
lipophilic T3 binds to
Alteration of receptor and form
transcription complex
gene, affect
mRNA Thyroid
receptor on
DNA
 The nongenomic actions of TH where interaction between components
cAMP, phosphatidyl inositol and protein kinases were observed

Sodium idodide Thyroglobulin

TSH-Stimulated symporter activity synthesis
Events at the
Thyroid Gland
Endocytosis and
Thyroperoxidase
hydrolysis of
Nongenomic synthesis Hormone
colloid and
synthesis
c-AMP Hormone secretion
mediated
events
Deiodinase activity
and Hypertrophy
 1) Drugs Inhibits hormones synthesis:
Propylthiouracil, Carbimazole
2) Inhibit Iodide trapping
Classification Thiocynates, Nitrates
based on 3) Inhibit hormone release
Pharmacology Iodine, Iodides of Na and K
4) Destroys thyroid tissue
Radioactive Iodine (131 I, 125 I)
 Hyperthyroidism Hypothyroidism

Classification of
Drugs used in
Treatment of
Levothyroxine
Hyperthyroidism Radioiodine
and Hypothyroidism (Le)

Thioureylenes /
Thionamide Liothyronine
(Carbimazole, (Li)
Propylthiouracil)

Liotrix (4:1
Iodine mixture Le:Li)
Radioiodine - First-line treatment for
hyperthyroidism
β rays short range,
absorbed by the 131Ihas a half-life of
tissue and produce
8 days Radioiodine -
131I(isotope) cytotoxic action to
Hypothyroidism
the cells of the avoided in
emits β and Y will eventually
thyroid
occur after children and in
rays follicles, resulting
treatment with pregnant ladies
in significant
radioiodine
destruction of the
tissue
 THIOUREYLENES
Carbimazole, Methimazole and Propylthiouracil

@ These drugs inhibit Carbimazole - converted Unwanted effects:

the iodination of tyrosyl to its active metabolite
residues in TG methimazole, plasma Neutropenia and
half-life of 6-15 h. agranulocytosis, Rashes,
@ Inhibit the Carbimazole produces headaches, nausea,
thyroperoxidase- more than 90% inhibition jaundice and pain in the
catalysed oxidation of thyroid incorporation
process joints
of iodine within 12 h
Treatment of Hypothyroidism (Hypo):

 Levothyroxine and liothyronine are synthetic compounds used

for Hypo.
 Similar to natural hormones, given through oral route.
 Thyroxine (sodium salt) - given in doses of 50-100 μg/day is the
usual first-line drug of choice.
 Liothyronine - faster onset and shorter duration of action, and
mainly used clinically for acute emergencies (myxoedema coma)
 Unwanted effects: precipitating angina pectoris, cardiac
dysrhythmias or even cardiac failure
 1. K.D Tripathi, MD. Essentials of Medical Pharmacology,
Seventh Edition.
References
2. HP rang, MM Dale, JM Ritter, RJ Flower and G.
Henderson. Rang and Dale's Pharmacology, Seventh
edition.

3. Charles R.Craig and Robert E.Stitzel. Modern

Pharmacology with Clinical Applications, Fifth edition.