lecture by dr Marwa Mahfouz

1. Thyroid hormone
By
Dr Marwa Mahfouz

2. Actions
• The thyroid gland facilitates normal growth and maturation by
maintaining a level of metabolism in the tissues that is optimal for
normal function
• as They are catabolic hormones and
increase the breakdown of fats (to FFA),
carbohydrates (cause hyperglycemia) and
proteins (cause weight loss). They are also
calorigenic and increase basal metabolic
rate (BMR).

3. Actions
• The two major thyroid hormones are triiodothyronine (T3; the most
active form) and thyroxine (T4).
Inadequate secretion of thyroid hormone
(hypothyroidism) leads to myxedema in
adults and bradycardia, cold intolerance,
and mental and physical slowing. In
children leads to cretinism, this can cause
mental retardation and dwarfism.

4. Actions
• By contrast, excess secretion of thyroid hormones (hyperthyroidism)
can cause tachycardia and cardiac arrhythmias (atrial fibrillation can
occur), body wasting, nervousness, tremor, and heat intolerance.

5. Thyroid hormone synthesis and secretion
• Thyroid gland contains follicular cells
and parafollicular (C) cells. Former
secretes thyroid hormones (T3 and T4)
whereas the latter is responsible for the
secretion of calcitonin.

6. Thyroid hormone synthesis and secretion
• The thyroid gland is made up of multiple
follicles that consist of a single layer of
epithelial cells surrounding a lumen
filled with thyroglobulin (the storage
form of thyroid hormone). Thyroid
function is controlled by TSH
(thyrotropin), which is synthesized by
the anterior pituitary.

7. Thyroid hormone synthesis and secretion
• Note:
• The hypothalamic thyrotropin
releasing hormone (TRH) governs
the generation of TSH.

8. Thyroid hormone synthesis and secretion
• Thyroid hormones are synthesized and stored in thyroid follicles in
the following manner:
• Iodine is first taken up in the
follicular cell with the help of
Na+: I– symporter (NIS).

9. Thyroid hormone synthesis and secretion
• Thyroid hormones are synthesized and stored in thyroid follicles in
the following manner:
• Iodine is first taken up in the
follicular cell with the help of
Na+: I– symporter (NIS).

10. Thyroid hormone synthesis and secretion
• Thyroid hormones are synthesized and stored in thyroid follicles in
the following manner:
• After entry in the follicular cells,
iodine is oxidized to form iodinium (I- )
ions. These ions combine with tyrosine
residues of thyroglobulin to form
mono-iodo tyrosine (MIT) and di-iodo-
tyrosine (DIT). This process is known as
organification of iodine.

11. Thyroid hormone synthesis and secretion
• Thyroid hormones are synthesized and stored in thyroid follicles in
the following manner:
• DIT combines with DIT to form tetra-
iodo-thyronine (T4) and with MIT to
form tri-iodo-thyronine (T3). This
process is known as coupling

12. Thyroid hormone synthesis and secretion
• Thyroid hormones are synthesized and stored in thyroid follicles in
the following manner:
• Oxidation, organification and
coupling reactions are catalyzed by
thyroid peroxidase enzyme.

13. Thyroid hormone synthesis and secretion
• Thyroid hormones are synthesized and stored in thyroid follicles in
the following manner:
• After formation, T3 and T4 are
transported to the follicles where these
remain stored as colloid. On
stimulation via TSH, these hormones
are released in the circulation.
In the liver and kidney, T4 is converted
to T3 (peripheral conversion) and taken
up by target tissues.

15. https://www.youtube.com/watch?v=11GrBJYlFjA

16. Treatment of hypothyroidism
• Main indication of thyroid hormones is hypothyroidism (cretinism,
myxedema and myxedema coma).
• Hypothyroidism usually results from autoimmune destruction of the
gland and is diagnosed by elevated TSH.
• Levothyroxine (T4) is preferred over T3
(liothyronine) or T3/T4 combination
products (liotrix) for the treatment of
hypothyroidism.

17. Treatment of hypothyroidism
• Levothyroxine is better tolerated than T3 preparations and has a
longer half-life. It is dosed once daily, and steady state is achieved in 6
to 8 weeks. Toxicity is directly related to T4 levels and manifests as
nervousness, palpitations and tachycardia, heat intolerance, and
unexplained weight loss.

18. Treatment of hypothyroidism
• Myxedema coma is an emergency situation, in which liothyronine
(only indication) can also be used (It should be used cautiously in
patients with heart diseases like AF).

19. Treatment of hyperthyroidism (thyrotoxicosis)
• Grave’s disease, an autoimmune disease that affects the thyroid, is
the most common cause of hyperthyroidism. In these situations, TSH
levels are low due to negative feedback. [Note: Feedback inhibition of
TRH occurs with high levels of circulating thyroid hormone, which, in
turn, decreases secretion of TSH.]

20. Treatment of hyperthyroidism (thyrotoxicosis)
• The goal of therapy is to decrease synthesis and/or release of
additional hormone. This can be accomplished by removing part or all
of the thyroid gland, by inhibiting synthesis of the hormones, or by
blocking release of hormones from the follicle.

22. Treatment of hyperthyroidism (thyrotoxicosis)
• 1. Removal of the thyroid
• This can be accomplished surgically or by destruction of the gland
with radioactive iodine (131I), which is selectively taken up by the
thyroid follicular cells.
• Most patients become hypothyroid
after radioactive iodine and require
treatment with levothyroxine.

23. Treatment of hyperthyroidism (thyrotoxicosis)
• 2. Inhibition of thyroid hormone synthesis (Thyroid Peroxidase
Inhibitors)
• Thyroid peroxidase enzyme catalyzes three reactions (oxidation,
organification and coupling) in the process of thyroid hormone
synthesis.
• Carbimazole, methimazole and
propylthiouracil act by inhibiting this
enzyme. PTU also blocks the peripheral
conversion of T4 to T3.

24. Treatment of hyperthyroidism (thyrotoxicosis)
• Note:
• These drugs inhibit the formation of new thyroid hormones but their
action manifests only when already stored pool of T3 and T4 is
utilized as they have no effect on thyroglobulin already stored in the
gland.

25. Treatment of hyperthyroidism (thyrotoxicosis)
• Note:
• Thus, a lag period of 1-3 weeks is present and clinical effects may be
delayed until thyroglobulin stores are depleted. These drugs can
rarely cause reversible agranulocytosis (most serious adverse effect)

26. Treatment of hyperthyroidism (thyrotoxicosis)
• Methimazole is preferred over PTU because it has a longer half-life,
allowing for once-daily dosing, and a lower incidence of adverse
effects.
• However, PTU is recommended during
the first trimester of pregnancy due to
a greater risk of teratogenic effects
with methimazole. PTU has been
associated with hepatotoxicity and,
rarely, agranulocytosis.

27. Treatment of hyperthyroidism (thyrotoxicosis)
• Note: Propylthiouracil has been found to be hepatotoxic and FDA has
declared methimazole as preferred drug over propylthiouracil for all
patients except in first trimester of pregnancy and lactation.

28. Treatment of hyperthyroidism (thyrotoxicosis)
• Thyroid peroxidase inhibitors are used for:
• the control of thyrotoxicosis in patients with
Graves’ disease and toxic nodular goiter.
• These are also used in young patients before
performing thyroidectomy.
• Another use of antithyroid drugs is to make the
patient euthyroid before application of
radioactive iodine.

29. Treatment of hyperthyroidism (thyrotoxicosis)
• 3. Inhibitors of Thyroid Hormone Release
• A pharmacologic dose of iodide inhibits the iodination of tyrosines
(“Wolff Chaikoff effect”), but this effect lasts only a few days.
https://www.youtube.com/watch?v=ZWnWvWoUW6M

30. Treatment of hyperthyroidism (thyrotoxicosis)
• 3. Inhibitors of Thyroid Hormone Release
• Sodium iodide, potassium iodide and Lugol’s solution act as ‘thyroid
constipating agents’ by inhibiting the release of T3 and T4 from
thyroglobulin.
• These drugs are the fastest acting anti-
thyroid drugs but is not useful for
long-term therapy; the thyroid ceases
to respond to the drug after a few
weeks.

31. Treatment of hyperthyroidism (thyrotoxicosis)
• 3. Inhibitors of Thyroid Hormone Release
• In sensitive individuals, acute reaction consisting of swelling of lips,
angioedema, fever, joint pain and petechial hemorrhages can occur.
Chronic overdose of iodides is called iodism.

32. Treatment of hyperthyroidism (thyrotoxicosis)
• 3. Inhibitors of Thyroid Hormone Release
Major symptoms are inflamed mucus
membranes, increase in secretions (salivation,
lacrimation and rhinorrhoea), headache,
rashes and gastrointestinal distress. These
drugs may also cause flaring up of acne in
adolescents.

33. Treatment of hyperthyroidism (thyrotoxicosis)
• 4. Drugs Causing the Destruction of Thyroid Gland
• I131 is the most commonly used radioactive iodine with a half-life of
8 DAYS (stable isotope of iodine is I127).
• When administered (as sodium salts,
orally), these are actively taken up by
the thyroid gland and stored in the
colloid. Concentration of radioactive
iodine by the thyroid gland is
responsible for its selective thyroid
destroying effect.

34. Treatment of hyperthyroidism (thyrotoxicosis)
• 4. Drugs Causing the Destruction of Thyroid Gland
• I131 can be used for the treatment of hyperthyroidism but response
is slow (maximum response may take 3 months). Thyroid peroxidase
inhibitors are administered to make the patient euthyroid.
• After a gap of 5 days (after stopping
anti-thyroid drugs), radioactive iodine
is given and thyroid peroxidase
inhibitor treatment is resumed till the
effect of I131 starts.

35. Treatment of hyperthyroidism (thyrotoxicosis)
• 4. Drugs Causing the Destruction of Thyroid Gland
• Radioactive iodine therapy is primarily indicated for
patients older than 35 years, those with heart
disease and in the presence of other contra-
indications of surgery. These drugs are not suitable
for young children and in the pregnancy. Another
disadvantage of radioactive iodine is that if
hypothyroidism develops, it is permanent (requiring
life long T4 therapy).

36. Thyroid storm
• Thyroid storm presents with extreme
symptoms of hyperthyroidism. The
treatment of thyroid storm is the same as
for hyperthyroidism, except that the drugs
are given in higher doses and more
frequently. β-Blockers, such as metoprolol
or propranolol antagonize the sympathetic
effects of thyrotoxicosis like tremors,
tachycardia, palpitations and anxiety.
Note:
Propranolol inhibits the peripheral conversion of T4 to T3