Thyroid gland

• The normal circulating thyroid hormones are Thyroxine T4 (90%),Triiodothyronine T3 (9%) and rT3 (1%).

• Reverse T3 (rT3) is biologically inactive form of T3.

• Thyrotoxicosis or hyperthyroidism (Graves disease) is the clinical syndrome caused by an excess of thyroid hormones.

• Hypothyroidism (Hashimoto's thyroiditis) is a clinical disorder in which there is a deficiency of thyroid hormones.

THYROID HORMONES

Increases basal metabolic rate.

Potentiates brain development.

Potentiates the beta effects of catecholamines.

Thyroid gland

Metabolism of thyroid hormones :• The primary metabolism of thyroxine is

deiodination.• Deiodination of T4 may occur by

monodeiodination of outer ring producing 3,5,3’- triiodothyronine - T3 ( T3 is 4 times more potent than T4) by 5’-monodeiodinase.

• Deiodination of inner ring produce 3,3’,5’ – reverse triiodothyronine – rT3 (inactive) by 5-monodeiodinase.

Outer ring Inner ring

5’-monodeiodinase. 5-monodeiodinase.

Thyroid hormones

Metabolism of Thyroid hormones :

• Drugs like beta blockers, high dose propylthiouracil and steroid inhibit the 5’-deiodinase activity necessary for conversion of T4 to T3 resulting in low T3 and high of rT3.

Thyroid gland

Mechanism of action of thyroid hormones :

• T4 dissociate from thyroxine binding globulin in plasma before entry into cells.

• In the cells, T4 is enzymatically deiodinated to T3 which enters nucleus and attaches to specific receptors which promotes protein synthesis.

Anti-thyroid drugs

Anti-thyroid drugs

Anti-thyroid drugs

Drugs used for the treatment of hyperthyroidism :

Inhibition of hormone synthesis :• Propylthiouracil and Methimazole.Blockade of hormone release :• Iodides, Iodinated contrast media. Radioactive Iodine 131Anion Inhibitors :• Perchlorates, Thiocynates.Beta blocking drugs : Propranolol.

Anti-thyroid drugs

peroxidase

Anti-thyroid agents

THIOAMIDES : • Inhibit hormone synthesis by

inhibiting peroxidase.• Propylthiouracil also inhibits

peripheral deiodination of T4 and T3.• Methimazole is more potent and

longer acting than propylthiouracil.• Slow in onset ~ 4 weeks.

Anti-thyroid drugs

THIOAMIDES : • These are used for treatment of

mild thyrotoxicosis and in preparation of surgery.

• Propylthiouracil is relatively safe and preferred in pregnancy.

Anti-thyroid drugs

THIOAMIDES : ADVERSE EFFECTS• Common adverse effects includes

maculopapular rash, arthralgia and vasculitis.

• Agranulocytosis – reversible.

Anti-thyroid drugs

Potassium iodide : Inorganic iodide• It blocks the organification and release

through inhibition of proteolysis – known as Wolff – Chaikoff effect.

• It decrease the size and vascularity – used before surgery.

• Rapid improvement in 2-5 days.• It is an ideal agent for the treatment of

severe thyrotoxicosis and preoperatively.

Anti-thyroid drugs

Potassium iodide : Inorganic iodide• Anti-thyroid effect is not for long term

as gland ‘escapes’ from its effect.• This is the most effective way of

limiting the potential damage to thyroid gland by radiation emergencies.

Anti-thyroid drugs

Potassium iodide : Inorganic iodide• Chronic use in pregnancy avoided –

fetal goiter.• Adverse reactions to iodine includes –

iodine induced thyrotoxicosis (Jod

Basedow’s phenomenon) at low doses.• Others includes – salivary gland

inflammation and acne.

Anti-thyroid drugs

Radioactive Iodine :• I-131 is the only isotope used in

treatment of thyrotoxicosis while others are used in diagnosis.

• Administered as sodium I–131 orally.• Therapeutic effect depends on emission

of beta rays – destroys the thyroid gland.

• Patients eventually becomes hypothyroid – managed with thyroxine.

Anti-thyroid drugs

Radioactive Iodine :• I–131 serves as alternative to

surgery.• Easy, effective, low cost and

absence of pain are the advantages.

• Not advisable for pregnant women.

Anti-thyroid drugs

ANION INHIBITORS :• Monovalent ions like perchlorate,

pertechnetate, thiocyanate can competitively block the uptake of iodine.

• Anion inhibitors are uncommon in use because of aplastic anemia.

• These are effective in iodine induced hyperthyroidism

Anti-thyroid drugs

Iodinated contrast media : Diatrizoate / Iohexol :

• They are valuable in hyperthyroidism and as adjunctive in thyroid storm.

• They inhibit the peripheral conversion of T4 into T3.

• Inhibition of hormone release is an additional mechanism.

Anti-thyroid drugs

Other Anti-thyroid drugs :• Propranolol is used in the

management of cardiac symptoms of thyrotoxicosis.

• Lithium is known to inhibit synthesis and release of thyroid hormones.

• Amiodarone can also result in hypothyroidism.

Thyroid gland

• The extreme manifestations of untreated hypothyroidism is myxedema coma with a mortality ~ 50%.

• Myxedema coma is treated with intravenous T4 or sometimes T3.

• Levothyroxine T4 is the best choice for replacement therapy.

• Thyroid hormones replacement is monitored by plasma TSH.

Thyroid gland

Thyroid storm: Thyrotoxic crisis, is an acute, life-threatening state induced by excessive release of thyroid hormones.

• Propranolol to minimize cardiac symptoms

• High-dose propylthiouracil is preferred because of its ability to inhibit peripheral conversion of T4 to T3

• Potassium iodide used to block the release of thyroid hormones