This document summarizes thyroid hormone synthesis and regulation. It discusses that the thyroid gland secretes three hormones: thyroxine (T4), triiodothyronine (T3), and calcitonin. T4 and T3 are synthesized through a process involving iodine uptake, oxidation, iodination of tyrosine residues, and coupling reactions. T4 has lower activity than T3, which is produced from peripheral conversion of T4. The hormones act through nuclear receptors to increase metabolism. The document also outlines treatments for hyperthyroidism including antithyroid drugs, iodine, beta blockers, and radioactive iodine, which destroy the thyroid tissue.

1. THYROID HORMONE
 Important for normal growth &
development and for energy
metabolism.
Front view

2. THYROID HORMONE
 Thyroid Gland secretes 3
hormones
Thyroxine (T4)
Triiodothyronin (T3) – Thyroid
hormones - produced by follicles
Calcitonin –
produced by interfollicular ‘C’ cells

3. RELEASE

4. SYNTHESIS AND RELEASE OF HORMONE
I. Uptake of plasma iodide by the
follicle cells (Iodide trapping)
II. Oxidation of iodide and iodination
of tyrosine (Oxidation & iodination)
III. Coupling
IV. Storage and release
V. Peripheral Conversion of T4 to T3

5. I. IODINE TRAPPING:
 Energy dependent process against
a gradient (Na+
/I-
symport; NIS)
 Trapping is also present in other
gland but not stimulated by TSH
II. OXIDATION & IODINATION:
 I-
to I+
with the help of H2O2 &
catalysed by peroxidase enzyme
 I+
combine with tyrosine to form
MIT and DIT

6. III. COUPLING:
 MIT and DIT couple together to form T3 and
T4
 Peroxidase enzyme catalyse
 Takes place in and facilitated by
Thyroglobulin (TG)
IV. STORAGE AND RELEASE:
 These thyroglobulin remains stored as
thyroid colloid in the interior of follicles
 Taken into cell by endocytosis; lysosomal
protease breaks down
 T3, T4 is secreted & MIT, DIT are deiodinated
and utilised

7. Coupling Reactions
DIT+DIT=T4
MIT+DIT=T3
Coupling Reactions
MIT+DIT=T3
DIT+DIT=T4
Thyroid Hormone Synthesis
NIS-Sodium Iodide Symporter, TPO-thyroid peroxidase

8. V. PERIPHERAL CONVERSION OF T4
TO T3:
 T3 (low concentration) is an active
form
 Liver & kidney convert T4 to T3
 Inhibitor - Propyl thiouracil,
propranolol (highdose), amiodarone
and glucocorticoids

9. TRANSPORTATION, METABOLISM &
EXCRETION:
 Highly plasma protein bound
Thyroxine binding protein (TBG),
Thyroxine binding prealbumin, Albumin
 Metabolised by deiodination and
conjugation in liver (kidney & salivary
gland)
 Metabolite undergo enterohepatic
circulation
 t1/2 of T4 = 6-7 days: t1/2 of T3 = 1-2 days

10. MOA: Both T3 and T4 penetrates cells by active
transport & binds to nuclear thyroid hormone
receptor bound to the thyroid hormone response
element (TRE)
Conformation changes occur (heterodimerization of
receptor with retinoid X receptor (RXR)) & releases
coreporessor and binding of coactivator occurs
Gene transcription induced production of specific
mRNA and proteins
Metabolic and anatomic effects.

11. MECHANISM OF ACTION

12. ACTIONS
 Affect whole body
Growth and development:
 Essential for normal growth & development
 Congenital deficiency- milestones of
development are delayed (mental retardation)
Metabolism
 ↑ BMR
 Lipolysis - ↑ free fatty acid, LDL level ↓
 Carbohydrate- ↑ peripheral utilization,
glycogenolysis, gluconeogenesis &
absorption - hyperglycemia
 Protein- Catabolism

13. CVS:
 ↑ Sensitivity & number of beta receptor -
↑HR, contractility and CO
Skeletal muscle:
 Hypothyroidism- flabby and weak
 Hyperthyroidism- ↑ muscle tone, tremor,
weakness
GIT: Propulsive activity ↑es with hormones
Haemopoiesis: Hypothyroidism- anaemia
Reproduction:
 Hypothyroidism- impaired fertility
Preparations:
 l-thyroxine sod. 25, 50, 75, 100 mcg- T4
(commonly used)

14. USES:
1. Cretinism:
2. Adult hypothyroidism:
 Symptoms
 ↓T3 & T4 and ↑TSH
 Levothyroxine - in empty stomach
 50 mcg ODX 3wks then 100mcg OD for 3
wks----- Davidson’ medicine
 ↓Weight & periorbital puffiness in 2-3weeks
Subclinical Hypothyroidism
3. Myxoedema coma:
4. Nontoxic goiter:

15.  Thyroid inhibitor- reduce thyroid
activity and hormonal effect
 Used in thyrotoxicosis
Thyrotoxicosis means an excess of thyroid
hormone in the body.
Graves' disease is the major cause of
hyperthyroidism. Other causes
include multinodular goiter, toxic
adenoma, inflammation of the thyroid &
taking too much iodine.
THYROID INHIBITORS

16. CLASSIFICATION
1. Hormone synthesis inhibitor (Antithyroid
drugs): Propylthiouracil, Carbimazole,
Methimazole
2. Ion trapping inhibitor: Thiocyanates,
Perchlorates, Nitrates
3. Hormone release inhibitor: Iodine,
Sod. and pot. Iodides
4. Destroy thyroid tissue: Radioactive
iodine (131
I, 125
I, 123
I)
PROLONG USE CAUSE HYPOTHYROIDISM:
Lithium, Amiodarone, Sulfonamide, Phenytoin,
Carbamazepine, rifampin, Phenobarbitone

17. ANTITHYROID DRUGS (Thioamides)
 MOA: Inhibit synthesis by binding to
peroxidase enzyme & preventing its
action
 Inhibit iodination of tyrosine residues in
thyroglobulin
 Inhibit coupling of iodotyrosine residues
to for T3 and T4
 Thyroid colloid is depleted over time and
blood levels of thyroid hormones are
progressively lowered.
 Propylthiouracil (PTU), in addition,
inhibit peripheral conversion of T4 to T3
 Carbimazole (prodrug) converts to

18. Antithyroid drugs Contd………
Pharmacokinetics
 Quick oral absorption
 Concentrate in gland – large Vd
 Enter milk, cross placenta
 Metabolised in liver
Adverse effects
 Reversible hypothyroidism & goiter on
overtreatment
 GI intolerance, skin rashes & joint pain-
important
 Loss or graying of hair, loss of taste, fever
& liver damage- infrequent
 Reversible agranulocytosis- rare but serious

19. Antithyroid drugs Contd………
Propylthiouracil Carbimazole
Less potent More potent
High plasma proteinLess plasma protein
bound bound
Less excrete in milk More
& less cross placenta
Short t1/2 Long t1/2
Multiple dosing Single dosing
No active metabolite Converts to
methimazole (active)
Inhibit peripheral No action
conversion of T4- T3

20. USES:
 Thyrotoxicosis
 Grave’s Disease
 Toxic Nodular Goiter
 Make patient euthyroid before
thyroidectomy
 Along with 131
I therapy

21. IODINE AND IODIDES:
 Fastest acting: initially cause “thyroid
constipation” ; but after 10-15 days, “thyroid
escape”
 MOA: Inhibition of hormone release- termed
as ‘thyroid constipation’
 Inhibits Endocytosis of colloid and
proteolysis of thyroglobulin.
 Excess of iodine inhibits its own transport
by interfering with expression of NIS
 Lugol’s iodine (5% iodine in 10 % potassium
iodide solution)

22. USES (iodine & iodide):
1. Preoperative preparation: 10 days before
thyroidectomy
2. Thyroid strom
3. Prophylaxis of endemic goiter
4. Antiseptic
ADVERSE EFFECT (iodine & iodide):
1. Acute reaction: Sensitive person- swelling of lip
& eyelids, fever, joint pain etc
2. Chronic overdose (iodism): Inflammation of
mucous membranes, salivation, rhinorrhoea,
sneezing, lacrymation, swelling of eyelids,
burning sensation in mouth, headache, rashes,
GI symptoms etc

23. RADIOACTIVE IODINE:
 131
I - therapeutic value
 125
I, 123
I - Diagnosis (rarely used)
 131
I emits γ rays & β particles
 β radiation (cytotoxic action) penetrate 0.5-
2 mm only
 Dose - calculated in millicurie
 MOA: Given single dose orally as sod 131
I –
concentrate in thyroglobulin→ β particles
destroy thyroid parenchyma (few weeks)

24. β ADRENERGIC BLOCKER:
 Propranolol, Metoprolol, Atenolol etc (without
intrensic sympathomimetic activity) – effective
adjuvant
 Quick symptomatic relief (palpitation,
tremor, nervousness, sweating, myopathy)
without altering hormone level
 Propranolol (widely used) in high dose
(160mg /day) reduce T3 level approx. 20% by
inhibiting peripheral conversion
 Uses: Thyrotoxic crisis, while awaiting
response to carbimazole or 131
I , preoperative
preparation before surgery