Presentation on theme: "Thyroid gland The normal circulating thyroid hormones are Thyroxine T4 (90%),Triiodothyronine T3 (9%) and rT3 (1%). Reverse T3 (rT3) is biologically inactive."— Presentation transcript:
1 Thyroid glandThe 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 is critical for growth and development of nervous system and musculoskeletal system.All the naturally occurring hormones are Levo (L) isomers.There is an absolute requirement of thyroid hormone during perinatal period for the development and maturation of nervous and musculoskeletal system.Thyroid hormone plays a major role in maturation of bone (epiphyseal centre).Thyroid gland also secrete calcitonin – serum calcium lowering hormone.
2 Increases basal metabolic rate. THYROID HORMONESIncreases basal metabolic rate.Potentiates brain development.Potentiates the beta effects of catecholamines.Both excess and deficiency of thyroxine can cause disorders.Thyrotoxicosis or hyperthyroidism (an example is Graves Disease) is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men.Hypothyroidism (an example is Hashimoto's thyroiditis) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.Clinical depression can sometimes be caused by hypothyroidism. Some research has shown that T3 is found in the junctions of synapses, and regulates the amounts and activity of serotonin, norepinephrine, and Gamma-aminobutyric acid (GABA) in the brain.
3 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 monodeiodinase.
5 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.
6 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.Non-nuclear – is due to T4 and are observed within minutes.
9 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.
11 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.Thioamides inhibit the enzyme thyroid peroxidase in the thyroid, reducing the synthesis of triiodothyronine (T3) and thyroxine (T4); block uptake of iodotyrosines from the colloid. They also block iodine release from peripheral hormone. Maximum effects occur only after a month since hormone depletion is caused by reduced synthesis, which is a slow process.
12 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.Slow in onset ~ 4 weeks because they do not inhibit secretion of hormones. These may exert immunosuppressive effects.Acts by inhibiting peroxidase and thus block coupling reaction and iodine organification.
14 Anti-thyroid drugs THIOAMIDES : ADVERSE EFFECTS Common adverse effects includes maculopapular rash, arthralgia and vasculitis.Agranulocytosis – reversible.
15 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.IODIDE SHOULD NOT BE USED ALONE BECOZ THE GLAND WILL ESCAPE FROM THE IODIDE BLOCK IN 2-8 WEEKS.Lugol's solution consists of 5 g iodine (I2) and 10 g potassium iodide (KI) mixed with 85 ml distilled water, to make a brown solution with a total iodine content of 130 mg/mL.
16 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.Administration of KI to inhibit the uptake and incorporation of radioactive iodine into the thyroid gland. CHRONIC USE OF IODIDE IN PREGNANCY SHOULD BE AVOIDED, SINCE THEY CROSS THE PLACENTA AND CAN CAUSE FETAL GOITER.
17 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.
18 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.Radioiodine is the most popular treatment for hyperthyroidism in the United States. This treatment takes advantage of the fact that thyroid cells are the only cells in the body which have the ability to absorb iodine. The majority of patients are cured with a single dose of radioactive iodine.The net effect is ablation of thyroid function over a period of 6 to 18 weeks.
19 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.
20 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
21 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.
22 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.
23 Thyroid glandThe 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.The principal manifestations of myxedema coma is deterioration of mental status.A common misconception is that a patient must be comatose to be diagnosed with myxedema coma. However, myxedema coma is a misnomer because most patients exhibit neither the nonpitting edema known as myxedema nor coma. Instead, the cardinal manifestation of myxedema coma is a deterioration of the patient's mental status. Myxedema coma is an extreme complication of hypothyroidism in which patients exhibit multiple organ abnormalities and progressive mental deterioration. The term myxedema is often used interchangeably with hypothyroidism and myxedema coma. Myxedema also refers to the swelling of the skin and soft tissue that occurs in patients who are hypothyroid. Myxedema coma occurs when the body's compensatory responses to hypothyroidism are overwhelmed by a precipitating factor such as infection. Patients with suspected myxedema coma should be admitted to an intensive care unit for vigorous pulmonary and cardiovascular support. Most authorities recommend treatment with intravenous levothyroxine (T4) as opposed to intravenous liothyronine (T3). Myxedema coma is treated with an initial IV T4 dose of 100 to 500 µg followed by 75 to 100 µg IV daily until the patient is able to take oral therapy.Because of the possibility of secondary hypothyroidism and associated hypopituitarism, hydrocortisone should be administered until adrenal insufficiency has been ruled out. Hydrocortisone should be administered intravenously at a dosage of 100 mg every eight hours.T4 has long half life ~7 days . It has a long half life and permit once a day dose.T3 is recommended only in the initial therapy of myxedema coma. Liothyronine T3 is having shorter half life and cardio toxic.
24 Thyroid glandThyroid storm: Thyrotoxic crisis, is an acute, life-threatening state induced by excessive release of thyroid hormones.Propranolol to minimize cardiac symptomsHigh-dose propylthiouracil is preferred because of its ability to inhibit peripheral conversion of T4 to T3Potassium iodide used to block the release of thyroid hormonesAdminister iodine compounds (Lugol iodine or potassium iodide) orally or via a nasogastric tube to block the release of THs (at least 1 h after starting antithyroid drug therapy). If available, intravenous radiocontrast dyes such as ipodate and iopanoate can be effective in this regard. These agents are particularly effective at preventing peripheral conversion of T4 to T3.Administer glucocorticoids to decrease peripheral conversion of T4 to T3. This may also be useful in preventing relative adrenal insufficiency due to hyperthyroidism.Lugol's iodine, also known as Lugol's solution, first made in 1829, is a solution of iodine named after the French physician J.G.A. Lugol. Lugol's iodine solution is often used as an antiseptic and disinfectant, a starch indicator, to replenish iodine deficiency, to protect the thyroid gland from radioactive materials (e.g. "fallout"), and for emergency disinfection of drinking water.Lugol's was often used in the treatment of gout and was used as a first line treatment for hypothyroidism in adults.It consists of 5% iodine and 10% potassium iodide (KI) in 85% distilled water with a total iodine content of 130 mg/mL. Potassium iodide makes the iodine water soluble through the formation of the I- ion. It is obtained from chemists and pharmacists who are licensed to prepare and dispense the solution.