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Role of the Thyroid gland  participates in normalizing growth and development and energy levels and the proper functioning and maintenance of tissues.

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Presentation on theme: "Role of the Thyroid gland  participates in normalizing growth and development and energy levels and the proper functioning and maintenance of tissues."— Presentation transcript:

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2 Role of the Thyroid gland  participates in normalizing growth and development and energy levels and the proper functioning and maintenance of tissues / organs  critical for the nervous, skeletal and reproductive tissues  it affects secretion and degradation rates of all hormones

3 Function of the Thyroid Gland  secretion of the following hormones:  triiodothyronine (T3) ; 59% iodine  tetraiodothyronine (T4; also known as thyroxine); 65% iodine  calcitonin

4 THYROID PHYSIOLOGY  Iodide Metabolism  The recommended daily adult iodide (I-) intake is 150 mcg  Biosynthesis of Thyroid Hormones  Transport of Thyroid Hormones  thyroxine-binding globulin (TBG)  about 0.04% of total T4 and 0.4% of T3 exist in the free form.

5 Biosynthesis of thyroid hormones

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7 Steps in Biosynthesis  Iodide trapping  Oxidation of iodide to iodine  Iodide Organification  Formation of T4 and T3  Release of T4 and T3

8 Peripheral metabolism of thyroid hormones The primary pathway for the peripheral metabolism of thyroxine (T4) is deiodination  deiodination of T4 may occur by monodeiodination of the outer ring, producing 3,5,3'-triiodothyronine (T3), which is three to four times more potent than T4

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10 Basic pharmacology of thyroid & antithyroid drugs Thyroid hormones A model of thyroid hormone action is depicted in Figure 38-4 Figure Regulation of transcription by thyroid hormones T3 and T4 are triiodothyronine and thyroxine, respectively. PB, plasma binding protein; F, transcription factor; R, receptor; PP, proteins that bind at the proximal promoter.

11 Hypothyroidism  A syndrome resulting from a deficiency of thyroid hormones and is manifested largely by a reversible slowing down of all body functions.  There is a striking retardation of growth and development.  In children, manifested as dwarfism and severe MR.

12 Synthetic Thyroid Hormone  synthetic levothyroxine (synthetic T4)  Brand names: Eltroxin, Euthyrox,Levoxyl, Levothroid, Synthroid  for hormone replacement therapy in hypothyroidism  DOSE  Infants and Children require more T4/Kg body weight than adults  Average dose for an infant micrograms/kg/d  Average dose for an adult – 1.7micrograms/kg/d  Once daily  Pharmacokinetics  should be taken 30min before or 1 hour after meals (delayed absorption for soy, other foods and drugs)  takes 6-8 weeks to reach steady state levels  Labs should be repeated after 2 months

13 Synthetic Thyroid Hormone  reasons for its use:  stability  content uniformity  low cost  lack of allergenic foreign protein  easy laboratory measurements of serum levels  long half-life (7days)  once a day dosing

14 Synthetic Thyroid Hormone  Uses  Hormone replacement therapy In young patients or those with mild disease- full replacement therapy started In older patients and in patients with cardiac disease -start treatment with reduced dosage  Myxedema Coma – medical emergency Loading dose – of T4 – micrograms I/V initially f/by `50micrograms daily I/V T3 – more cardiotoxic and difficult to moniter  Hypothyroidism and Pregnancy – daily dose –adequate

15 Synthetic Thyroid Hormone  synthetic liothyronine (synthetic T3) is 3-4x more potent  (Cytomel,Triostat)  not used alone for long term treatment secondary to short half life and large peaks in serum T3 levels  increase risk for cardiac side effects secondary to hyperthyroid states during treatment

16 Hyperthyroidism  A thyroid disorder caused by an antibody- mediated auto-immune reaction, but the trigger for this reaction is still unknown  most common cause of hyperthyroidism

17 Anti-thyroid Drugs  Thioamides  Iodides  radioactive iodine  Beta adrenoceptor blocking agents

18 Mechanism of action of anti thyroid drugs

19 Biosynthesis of thyroid hormones

20 Thioamides  Methimazole  Propylthiouracil (PTU) Carbimazole  MOA:  inhibit synthesis by acting against iodide organification (both)  coupling of iodotyrosines (both)  Blocks peripheral conversion of T 4 to T 3 (PTU)

21 Thioamides  Pharmacokinetics:  almost completely absorbed in the GIT  serum half life: 90mins(PTU) ; 6 hours (methimazole)  excretion: kidney – 24 hours (PTU) ; 48 hours (Methimazole)  can cross placental barrier (lesser with PTU)  Methimazole 10x more potent than PTU  PTU more protein-bound

22 Thioamide uses  Definitive therapy  Graves disease  Toxic nodular goitre  Preoperatively  In thyrotoxic patients  Along with RAI

23 Thioamides  Adverse Effects:  maculopapular rash  benign transient leukopenia  agranulocytosis  hepatitis (PTU) ; cholestatic jaundice (Methimazole)  vasculitis  lupus-like syndrome

24 Iodine 131  preparations: sodium iodide 131  MOA: trapped within the gland and enter intracellularly and delivers strong beta radiations destroying follicular cells  Penetration range µm  Clinical uses: Grave’s, primary inoperable thyroid CA  Contraindication: pregnancy

25 Iodine 131  Advantages  Easy administration  Effectiveness  Low expense  Absence of pain

26 Iodine 131  Thioamides should be given initially and stop 5-7 days before radioactive iodine administration  131 I dosage generally ranges between uCi/g of estimated thyroid wt. corrected for uptake. May be repeated after 6 months  Adverse effects  permanent hypothyroidism  potential for genetic damage  may precipitate thyroid crisis

27 Anion Inhibitors  Monovalent anions such as perchlorates, pertechnetate and thiocyanate can block uptake of iodide by the gland by competitive inhibition  can be overcome by large doses of iodides  useful for iodide-induced hyperthyroidism (amiodarone-induced hyperthyroidism)  rarely used due to its association with aplastic anemia

28 Biosynthesis of thyroid hormones

29 Inorganic Iodines  major anti-thyroids before the introduction of thioamides (1950s)  preparations:  strong iodine solution (Lugol’s)  potassium iodide  iodone

30 Inorganic Iodines  MOA:  acutely blocks release of thyroid hormone from the gland by inhibiting thyroglobulin proteolysis  inhibit iodide organification  Uses:  useful in thyroid storms: 2-7 days  Preoperatively - iodides decrease vascularity, size and fragility of hyperplastic gland  Caution:  it may delay onset of thioamide effects; should be given after initiation of thioamides  The gland will escape from inhibition after 2-8 weeks.

31 Iodinated Contrast Media  Iodinated contrast media Ipodate (oral) Iopanoic acid (oral) Diatrizoate (intravenous) valuable in hyperthyroidism (but is not labeled for this indication)  MOA: inhibits conversion of T4 to T3 in the liver, kidney, brain and pituitary Another MOA is due to inhibition of hormone release secondary to iodide levels in blood  Useful in thyroid storms (adjunctive therapy)

32 Beta Blockers  Drugs: Propranolol, Metoprolol, Atenolol  MOA:  Membrane-stabilizing action: inhibits T 4 to T 3  Ameliorate many disturbing s/sxs of hyperthyroidism secondary to increased circulating catecholamines by blocking beta receptors  Indications: Grave’s, Thyroid storm

33 Corticosteroids  Prednisone is given for patients with Grave’s ophthalmopathy  1mg/kg/day (60mg/day 3 divided doses); if it should be given for more than 4 weeks, taper to decrease risk of adrenal crisis

34 Thyroid storm  Sudden exacerbation of throtoxic symptoms  Life threatening condition  Vigorous management  Propanalol 1-2mg i/v or 40-80mg PO Q6h  Diltiazem mg Po Q8-6 hrs or 5-10mgs intravenous infusion/hour

35 Thyroid storm  Potassium iodide  Propylthiouracil  Hydrocortisone  Supportive therapy  Plasmapheresis/peritoneal dialysis

36 Hyperthyroidism and Pregnancy  Ideal situation- treat before pregnancy  Pregnancy-Radioactive iodine CI  Propylthiouracil  Dose limitation≤ 300mgs/day  Methimazole alternative- fetal scalp defects


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