2. Thyroid
•Thyroid gland is one of the largest gland
and highly vascularized endocrine gland
present in the body.
•It is a flat structure containing two lobes
joined by isthmus.
•It is situated anteriorly above the trachea
and just below the larynx.
•A glycoprotein know as thyroglobulin is
the main constituent,with a high
molecular weight that binds the iodine
present in organic form.
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3. • Thyroglobulin upon hydrolysis releases thyroid hormone,
which are considered to be iodinated tyrosine derivatives, as
they are derived from l-tyrosine.
• Thyroid gland is controlled and maintained by pituitary gland
and hypothalamus.
• This gland secretes three main hormones know as
Thyroxine (T4),triiodothyronine(T3), and calcitonin.
• The thyroid hormone (T3 and T4) are non-steroidal in nature
and are chemically regarded as the amino acid containing
iodinated diphenyl ethers.
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4. • Thyroxine(T4) is the major form of thyroid hormone found in
circulation.
• The ratio of thyroxine and triiodothyronine released in to the
blood circulation is 20:1
• Thyroid gland also secretes calcitonin that is responsible for
maintaining calcium homeostasis.
• Calcitonin is produced by the parafollicular cells of the thyroid
gland.
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5. Bio-synthesis, storage and release
• It is a complex process.
• The thyroid hormones are synthesized and stored as amino acid
residues of thyroglobulin, which upon hydrolysis release the
thyroid hormones.
• The inorganic form of iodine supplied through diet also play a
significant role in the production of thyroid hormone.
• Biosynthesis of thyroid hormone is regulated by fluctuations in
plasma levels of thyroid stimulating hormone/thyrotropin.
• Thyrotropin inturn regulates the synthesis of thyroglobulin,
hydrogen peroxide and thyroperoxidase(TPO).
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6. Steps involved in conversion of inorganic iodide
to thyroid hormone are
Uptake of iodide by the follicular cells of thyroid gland.
Oxidation of iodide.
Iodination of tyrosyl residues/formation of iodotyrosyl residues.
Formation of thyroxine and triiodothyronine from iodotyrosine
by coupling reaction.
Release of T3 and T4 by proteolysis of thyroglobulin.
Conversion of T4 to T3.
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7. Mechanism/mode of action
• Thyroid hormone diffuses a cross the cell membrane and bind to
intracellular thyroid receptors.
• After the penetration T4 gets converted to T3, which has high affinity
for the thyroid receptors.
• A specific DNA sequence is identified ,and T3 bind to it.
• The receptors undergo a change in their conformation ,which
stimulates transcription, results in the synthesis of proteins,
ultimately stimulating function of T3 and T4
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8. • Thyroid works on a delicate feedback mechanism.
• T3 and T4 synthesis in thyroid is regulated by TSH.
• If the circulation levels of T3 and T4 are high then
pituitary gland decreases its sensitivity to TSH,
which is secreted by hypothalamus.
• This entire process make synthesis and release of
TSH low by negative feedback mechanism.
• If the T3 and T4 levels are low the Pituitary gland
becomes more sensitive to thyroid regulating
hormone(TRH), which is secreted by the
hypothalamus.
• This stimulates TSH secretion with the release of
excess thyroid hormones.
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9. • Thyroid gland converts iodine present in food in to thyroid
hormones like T4 and T3.
• The thyroid cells absorb iodine and combine the iodine with
tyrosine amino acid to form T4 and T3.
• Thyroid hormones are responsible for proper functioning,
development and differentiation of all the cells of human body.
• They also helpful in regulating fats, proteins, carbohydrates and
vitamine metabolism.
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10. Differences between T3 and T4
T3 T4
Four time more potent than T4 Less potent
Peak effect reaches with in 24-48 hrs. Peak effect reaches in 6-8 hrs
Plasma protein binding capacity is less It bind more tightly to plasma proteins
It is active in vitro It is inactive invitro
Thyroid gland produce 20% of T3 Thyroid gland produces 80% of T4
T3 is the active form T4 is less active than T3
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11. THYROID DISORDERS
Thyroid dysfunctioning results in many unwanted changes
in metabolisum of proteins, carbohydrates,lipids .
It also exerts adverse effect on reproductive, Gastro-intestinal,
central nervous system ,and cardiovascular system.
Two types of thyroid disorders are:
• Hypothyroidism
• Hyperthyroidism
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12. Hypothyroidism
• It occur due to the deficiency of thyroid hormone.
• Common symptoms include decreased metabolic rate increase levels of serum
cholesterol, fatique, lethargy, mental retardation etc.
Common types of hypothyroidism include:
1. Cretinism
• Decrease in the levels of thyroid hormone in infants or during foetal stage is
know as cretinism.
Reasons for occurrence
Extreme deficiency of iodine
Failure of thyroid development
Defect in synthesis of thyroid hormones
Presences of thyroid stimulating hormone receptor blocking antibodies.
Symptoms
Yellowskin, potbelly, dwarfism, physical and mental retardation.
Treatment
It can be treated by thyroxine . 12
13. 2. Myxedema
• It is a condition in which hypothyroidism results in accumulation
of mucopolysaccharide in the intercellular spaces of muscle and
skin.
Reasons for occurances
• Glandular tissue degeneration
• Improper pituitary feed back mechanism.
• Impairment in the secretions of synthesized hormones.
• Impariment in biosynthesis of hormones
• Excessive use of antithyroid drugs.
symptoms
• Dry skin, slow pulse, mental retardation, weight gain, intolerances
to cold, deep hoarse voice.
Treatment
• Administration of liotrix.(it is a mixture of levothyroxine sodium
and liothyronine sodium in 4:1 ratio.
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14. 3. Myxedema coma
• When hypothyroidism is left untreated for prolonged period of
time ,it results in myxedema coma. it mainly occur in old people
and during cold climatic conditions.
Reasons for occurance
• Neglecting the condition of hypothyroidism by providing
inadequate treatment.
• Pulmonary infection, trauma, congestive heart failure, Prolonged
exposure to cold.
Symptoms
• Coma, bradycardia, decrease in body temperature,
hypotension, urinary retention, pleural and peritoneal effusions,
respiratory depression, dry and rough skin.
Treatment
• Thyroxine sodium (150-300mcg) ,and triiodothyronine (10mcg).
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15. 4.Simple(non-toxic) Goitre
• The word goitre refers to the enlargement of thyroid gland occur due
to the deficiency of thyroid hormone production ,which ultimately
results in excess realease of TSH.
The non-toxic goitre is of two types :
• Endemic goitre : occur due to the dificiency of iodine
• Sporadic goitre : occur due to the impariment in synthesis of
hormones
Reasons for occurance
• Lack of dietary iodine.
• Excessive use of goitrogens.
Symptoms
• Enlargement of the neck, weight gain etc.
Treatment
• Iodine + 5-8-mg sodium iodate per kg of common salt 15
16. 5. Adult hypothyroidism.
• Hypothyroidism that occur as a result of thyroiditis, thyroidectomy is referred to as adult
hypothyroidism
Reasons for occurrence
• Thyroiditis, throidectomy
• Excessive use of drug like I131,lithium,amiodarone and iodides.
Symptoms
• Physical and mental retardation, decreased metabolic rate lethargy etc.
Treatment
• L-thyroxine (50 microgram) in initial days
Increase the dose up to 100-200micro gram/day.
6. Hashimoto’s disease/auto-immune thyroditis with hypothyroidism.
• It is an auto-immune disorder in which the thyroid gland gets destructed by the attack of
lympocytes, plasma cells and fibrous tissue.
Reasons for occurrence
• Injury to thyroid gland
• Production of auto antibodies.
Treatment
• Thyroid hormone replacement therapy
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17. Hyperthyroidism
• Occur due to the excess activity of thyroid hormones.
• Excessive intake of thyroid hormone causes thyrotoxicosis.
General symptoms of hyperthyroidism includes, increased heart rate and cardiac output due to
the increase in oxygen demand, increased metabolic rate, decreased levels of serum
cholesterol, intolerance to glucose,glucosuria, anorexia,intolerance to thermoregulation.
Graves disease
• It is autoimmune disorder.
• Occurs due to the presence of autoantibodies.
• igG antibodies produced by the body bind to the TSH receptor on thyroid gland instead of
TSH.
• This binding stimulates the realease of thyroid hormones and ultimately results in excess
production of thyroid hormones.
• The binding of auto antibodies to the TSH receptor is not controlled by any negative
feedback mechanism as in the TSH.
Reasons for occurrence
• Production of autoantibodies
• Excess production of thyroid hormones.
Symptoms
• Enlargement of thyroid gland,patient becomes hot and flushed.
Treatment
• Use of antithyroid drugs
• By using radioactive iodine
• By using surgery(thyroidectomy)
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18. Toxic uninodular/multinodular goitre
• The adenomas grow excessively and result in increased secretions of thyroxine
and triiodothyronine.it mainly occurs in elderly patients.
Thyroid storm/thyroid crisis/thyrotoxic crisis
• Extreme hyperthyroidism is referred to as thyroid storm.
Reasons for occurance
• Lack of proper treatment
Symptoms
• Hyperpyrexia, tremors,mania,heart failure,
• tachycardia, vomiting, jaundice, hepatomegaly,coma.
Treatment
Initial treatment with high dose of antithyroids PTU-1200mg and then
treatment with beta-blockers and iodine
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19. Treatment for Hyperthyroidism
• Anti-thyroid drugs—Inhibits thyroid hormone synthesis by irreversibly
binding to TPO inhibiting its ability to break down iodine (I2→I-) and
covalently attach it to the tyrosine residue of thyroglobulin.
– Propylthiouracil
– Methimazole
– Carbamizole─Degraded to methimazole in the body.
• Radioactive Iodine.
• Thyroidectomy.
• β-Blockers used in the treatment of thyroiditis to treat symptoms.
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20. Anti-thyroid Drugs
• Effective in the long-term treatment of hyperthyroidism.
• 6-8 weeks before maximum effect of the drug achieved.
Drug inhibits hormone synthesis, so hormones synthesized
prior to drug use will continue to cause hyperthyroid
condition.
• Typical side effects include headache, nausea, vomiting,
itchy skin and rash, and muscle aches and pains.
• Serious liver damage, decreased red and white blood cell
synthesis, as well as decreased platelet production have
been reported in a few cases. The drug’s interaction with
other enzymes responsible for clotting factor synthesis
accounts for some of these serious side effects.
• Administering too high a dosage of anti-thyroid drugs can
cause hypothyroidism.
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28. Iodine131
• Thioamides should be given initially and stop 3 days
before radioactive iodine administration
• 131I dosage generally ranges between 185 MBq to
555MBg repeated after 6 months
• Adverse effects
– permanent hypothyroidism
– potential for genetic damage
– may precipitate thyroid crisis
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29. Anion Inhibitors
• Monovalent anions such as perchlorates,
pertechnetate and thiocyanate can block uptake of
iodide by the gland by competitive inhibition
• can be overcome by large doses of iodides
• useful for iodide-induced hyperthyroidism
(amiodarone-induced hyperthyroidism)
• rarely used due to its association with aplastic
anemia
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30. Iodinated Contrast Media
• Iodinated contrast media
Ipodate (oral)
Iopanoic acid (oral)
Diatrizoate (intravenous)
valuable in hyperthyroidism (but is not labeled for this
indication)
• MOA: inhibits conversion of T4 to T3 in the liver, kidney, brain
and pituitary
Another MOA is due to inhibition of hormone release
secondary to iodide levels in blood
• Useful in thyroid storms (adjunctive therapy)
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31. Beta Blockers
• Drugs: Propranolol, Metoprolol, Atenolol
• MOA:
– Membrane-stabilizing action: inhibits T4 to T3
– Ameliorate many disturbing hyperthyroidism
secondary to increased circulating catecholamines
by blocking beta receptors
• Indications: Grave’s, Thyroid storm
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32. Corticosteroids
• Prednisone is given for
patients with Grave’s
ophthalmopathy
• 1mg/kg/day (60mg/day
3 divided doses); if it
should be given for more
than 4 weeks, taper to
decrease risk of adrenal
crisis
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33. Thyroid storm
• Sudden exacerbation of throtoxic symptoms
• Life threatening condition
• Vigorous management
– Propanalol 1-2mg i/v or 40-80mg PO Q6h
– Diltiazim 90-120mg Po Q8-6 hrs or 5-10mgs
intravenous infusion/hour
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34. TSH Replacement Drugs
• Thyrotropin alpha—A synthetic form of TSH. Administered
intravenously.
• Used in thyroid cancer treatment.
– Tumors of the hypothalamus or pituitary gland can cause the
uncontrolled release of TSH, which accumulates in the thyroid and can
cause subsequent follicular or papillary cancer of the thyroid. Partial
or total thyroidectomy typical.
– Following thyroidectomy, the individual is dependent on exogenous
thyroid hormones to regulate metabolism, but thyrotropin alpha is
also used to suppress the release of endogenous TSH, which could
trigger cancerous growth again.
– Used as a diagnostic tool to determine the reoccurrence of cancer.
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35. Hyperthyroidism and Pregnancy
• Ideal situation- treat before pregnancy
• Pregnancy-Radioactive iodine CI
• Propylthiouracil
– Dose limitation≤ 300mgs/day
• Methimazole alternative- fetal scalp defects
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