This is lecture on thyroid hormone synthesize, physiological action and replacement therapy in hypothyroidism.

1. Dr. Kiran G. Piparva
Assistant Professor, Pharmacology
All India Institute of Medical
Science, Rajkot
Date: 23/11/2022

2. THYROID HORMONES
T4 - THYROXINE –
Tetra iodothyronine
T3 - Tri iodothyronine
Thyroid hormone
Follicular cells
C cells- Calcitonin

3. Synthesis of Thyroid hormones
From
circulation to
within thyroid
gland

4. I-
H2O2
HOI/
E-OI
I+
DIT
Tg
MIT
T4 T3
Tg
Tg
T3
T4
DIT MIT
MIT
DIT
I-
I-
+
peroxidase
peroxidase
NIS
pendrin
T4
T3
DIT
MIT
proteolysis
endocytosis
T3 T4
T3
deiodinase
Apical
basolateral
blood
colloid
follicular
cell
1/5 of total
TSH
TSH

5. MIT + DIT - T3
DIT + DIT - T4
COUPLING reaction catalyzed by PEROXIDASE
PEROXIDASE deficiency:
Congenital hypothyroidism

6. Transport of Thyroid Hormones in the
Blood
Thyroxine-binding globulin
Transthyretin
Albumin
T4 → (1/3)T3 (liver/ kidney) –
T4 → reverse T3 (inactive ) - deiodinase 1 & 2

7. Iodide Uptake
Oxidation of iodide -- thyroid peroxidase
the iodination of tyrosyl groups of thyroglobulin
-- MIT , DIT
coupling of iodotyrosine – formation of T3,T4 By thyroid
Peroxidase
Endocytosis →Proteolysis – release
of T4 , T3 in blood
T4 → T3 (peripheral conversion ) - deiodinase

8. T3
Less synthesis in thyroid
Biologically active
T1/2 = 1day
Rapid action
T4
MORE synthesis in thyroid
Biologically inactive
T1/2 = 7 days
Slow action

9. Regulation of thyroid function
Somatostatin

10. Receptors = Nuclear Receptors
Situated within Nucleus
TRE

11. Physiological Functions
Growth &
Development of body
CNS development
Deficiency - CRETINISM
Catabolic
effects

12. Physiological Functions
Thermogenic Effect
BMR
• Maintain body temperature
• uncoupling of oxidative phosphorylation
CVS - hyperdynamic circulation
- Direct action- upregulation of beta
receptors
↑ HR , CO , BP

13. METABOLIC EFFECTS
↑ protein use as energy - Catabolic effect
Nitrogen balance , tissue wasting , weight loss --
hyperthyroidism
LIPID - ↑ lipolysis , Cholesterol metabolism accelerated
Carbohydrate
metabolism ↑ , gluconeogenesis + glycogenolysis ↑
Hyperthyroidism – insulin resistance + hyperglycemia

14. CNS: Prefund effect – cretinism –mental retardation
Hyper: anxious, Hypo –sluggish
Skeletal muscle tone - ↑ tone in hyper, low in
hypothyrodism
GIT: increase movement in hyper, Constipation in
hypothyroidism
Kidney: only affected in extreme
Hemopoiesis: Thyroid hormone facilitate
Reproduction: Indirect effect- impaired in hypothyrodism

15. Disorders of thyroid hormones
• Hypothyroidism:
• low circulating free thyroid hormone
– Primary (thyroid origin)
• Low T4, T3, free thyroid
hormones
• High TSH
– Secondary (hypothalamus/
pituitary origin)
• Low T4, T3, free thyroid
hormones
• Normal/low TSH
•Hyperthyroidism:
High circulating free
thyroid hormone
• Primary/secondary
• High T4,T3 but low
TSH

18. Thyroid hormones as
REPLACEMENT THERAPY - Hypothyroidism
L – THYROXINE = L-T4
Oral + IV
Liothyronine = L-T3
CRETINISM
deficiency in childhood
ADULT hypothyroidism - MYXEDEMA
-Hashimoto’s thyroiditis = circulating antibodies directed
against thyroid peroxidase / Tg
-Thyroidectomy , after radioactive iodine

19. Myxedema coma
syndrome that represents the extreme expression of
severe, long-standing hypothyroidism
1. hypothermia
2. respiratory depression
3. decreased consciousness
Rapid replacement
L- T4
= 200-800 mcg IV than 1oo mcg /day
L-T3 can be used also
ABC of emergency
steroids

20. Thyroid hormones - Uses
1. Cretinism: (infancy/childhood) : Failure of thyroid
development/ defective synthesis (sporadic cretinism)/
severe iodine deficiency (endemic cretinism) -
irreversible neurological damage
• Start treatment as soon as diagnosed to avoid
• T4thyroxine- 12.5–50 mcg (6–8 mcg/kg)/ day; life long
• Dose- adjusted clinically/ T4 level 9-12 mcg%
• In hypo pituitary hypothyroidism with ACTH deficiency;
give glucocorticoid first

21. Thyroid hormones - Uses
2. Myxoedema: (adult hypothyroidism):
• Causes: Autoimmune Thyroiditis (Antibodies against thyroid
peroxidase or thyroglobulin)/ thyroidectomy/ drugs (I131,
iodides, lithium, amiodarone )/ Iodine deficiency
• T4 - DOC - start 50 mcg/day ; increase every 2-3 wks (100-200
mcg/day)- Further adjustment at 4-6 wks for steady state
• In IHD start with 12.5 mcg/day dose; low dose; risk of
precipitation
• Dose is adjusted by clinical response & normalization of TSH
levels.
• Lethargic, obese, pregnant need higher doses

22. • Subclinical hypothyroidism:
– Euthyroid status
– Normal free serum thyroxine level (≥ 9 pmol/L) but
– Raised TSH level (>10 mU/L)
– Treatment with T4
– TSH levels 6-10 mU/L – replacement therapy optional

23. Thyroid hormones - Uses
3. Myxedema coma: Emergency treated in ICU: high mortality
• Progressive mental deterioration, Rapid thyroid replacement –
crucial
• Liothyronine (T3) -100 mcg iv stat f/b 25 mcg 6 hrly
OR
• L-thyroxine (T4)- 200-500 mcg iv f/b 100 mcg/day iv OD till oral
therapy started
• Glucocorticoids IV (to cover adrenal insufficiency)
• Prophylactic antibiotics; if required
• Slow warming with blankets
• Respirator for hypoventilation,
• correction of hyponatremia and hypoglycemia

24. 4. Nontoxic goiter:
• Endemic (iodine deficiency) or Sporadic (defective synthesis) -
raised TSH levels
• Endemic: enhanced by excess calcium in water, food or milk
(goitrin, thiocynates)
• Raised TSH  thyroid enlargement  more trapping of
iodine, more T3  enough hormone to meet demands 
clinically euthyroididm
• T4 – 100-200 mcg/day- decreases size of goiter
• Good response- recent, diffuse, soft goiter cases
• Poor response- old, fibrotic, nodular goiter
• 1-2 yrs therapy in diffuse puberty goiter but some require life
long treatment

25. Practical 26. ENDOCRINE SYSTEM
• Exercise-1:
• A 30 years old female patient complains of fatigue, cold
intolerance, mental slowness, dry skin, constipation, muscle
aches and irregular menses for past 2 months. On clinical
examination she has bradycardia, delayed relaxation phase of
deep tendon reflexes and hypotension. Investigation shows
decreased serum T3 and T4 levels. Diagnosis: Hypothyroidism.

26. • Rx
• Tablet thyroxin 25ug
• Dispense such 30 tablets
• Take one tablet at empty stomach at early morning
• Follow up after one month

28. Follicular cells - T4 , T3 (active )
Synthesis – Uptake , Oxidation , Iodination , Coupling , Endocytosis ,
Proteolysis , release , T4 →T3
Transport , Inactivation (reverse T3 )
Receptors – Nuclear , in the nucleus → T3 - active – short acting
Growth + CNS development Thermogenesis Protein / Lipid /
Carbohydrate
Replacement – cretinism / adult hypothyroidism / Myxedema coma