25/10/56. Hypothyroidism Myxedema in adults Cretinism congenital deficiency of thyroid hormone Hashimoto thyroiditis. Simple goiter (nontoxic goiter)

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1 THERAPEUTIC USES OF THYROID HORMONE Supeecha Wittayalertpunya Wannarasmi Ketchart Nov 2013 Hyperthyroidism (Thyrotoxicosis) Grave s disease (diffuse toxic goiter) Toxic uninodular & Toxic multinodular goiter Thyroid storm (severe) sudden acute exacerbation Hypothyroidism Myxedema in adults Cretinism congenital deficiency of thyroid hormone Hashimoto thyroiditis Simple goiter (nontoxic goiter) Euthyroidism 1

2 Therapeutic use of Thyroid hormone Hypothyroidism and simple goiter Thyroid hormone replacement and suppression therapy Hyperthyroidism Antithyroid drugs 1. Replacement therapy for Hypothroidism Myxedema Cretinism Hashimoto thyroiditis 2. TSH suppression therapy for decrease enlargemet of thyroid gland Nontoxic goiter (Simple goiter) Radioactive Iodide Surgery Destroy thyroid cells น ยมใช T 4 มากกว า T 3 เพราะ ค าคร งช ว ตยาวกว าและ T 4 เปล ยนเป น T 3 ได ในร างกาย Restlessness End state of untreated hypothyroidism weakness, stupor, hypothermia,hypoglycemia, hypoventilation, water intoxication shock R x death Levothyroxine (T 4 ) IV, Oral form Insomnia Nervousness Tachycardia Heat intolerance Weight loss Osteoporosis Cardiotoxicity In elderly patients 2

3 GRAVES DISEASE Perchlorate Thiocyanate Pertechnetate I - Na + Extracellular space Thyroid peroxidase (organification) Follicular cell Thyroid peroxidase (coupling) Colloid space TG I - Na + TG MIT TG DIT T3 T4 T G Iodides I - (high) 131 T3, T4 T 3 Propylthio uracil T 4 Peripheral conversion T 3 Thioamines Iodides (high) MATABOLIC STEP A lodide uptake B Organification C Coupling reaction D Secretion (proteolysis) E Peripheral conversion by 5 deiodinase T 4 T 3 Ionic Inhibitors Thioamides Iodide Radioactive Iodine 3

4 SITES OF ACTION AND EFFECTS OF ANTITHYROID AGENTS THIOAMIDES: PROPYLTHIOURACIL(PTU) AND METHIMAZOLE Thyroid hormone synthesis and actions Active accumulation of iodide into gland Iodide uptake by sodium-iodide symporter Iodination of tyrosyl residues on thyroglobulin Coupling reactions to form DIT, T 3 and T 4 Proteolytic release of T 4 and T 3 from thyroglobulin Conversion of T 4 to T 3 via 5 deiodinase in peripheral tissues Effects of antithyroid agents Basis for selective cell destruction of 131 I Ionic inhibitors Inhibited by thioamides Inhibited by thioamides and high levels of iodide Inhibited by iodide Inhibited by propranolol, and at high-dose propylthiouracil Use in uncomplicated hyperthyroid conditions Slow onset High dose PTU inhibits 5 deiodinase Common SE: maculopapular rash Serious SE: agranulocytosis, hepatotoxicity, vasculitis PTU causes more SE PTU is safer in pregnancy. (Both drugs cross the placental barrier, PTU is extensively protein bound) Currently used more metimazole in pregnancy Inhibit Iodide uptake Inhibit thyroid hormone synthesis and release (short effect) decrease size and vascularity of thyroid gland Use Preoperative operation thyroid gland ใช ร วมก บยาอ น ร กษาภาวะ thyrotoxic crisis ร ปยา : Lugol s solution, Saturated Solution KI (SSKI) Use in Hyperthyroidism : Ageing : with CVS disease : Toxic nodular goiter : Recurrent Side effect : Hypothyroidism (80%) Contraindication : pregnancy, children 4

5 Propranolol, Atenolol l symptomatic treatment inhibit catecholamine like effect from Thyroid hormone Acute and severe Hyperthyrodism death R x Propranolol control CVS SSKI inhibit Thyroid hormone release PTU inhibit Thyroid hormone synthesis Other - steroid prevent shock - supportive treatment EFFECT OF CALCITONIN, PTH AND VITAMIN D ON CALCIUM HOMEOSTASIS THERAPEUTIC USE OF PARATHYROID HORMONE Intestinal absorption of calcium Renal excretion of calcium bone Effect on plasma calcium calcitonin postpradial mineralization PTH indirect resorption resorption Vitamin D (1,25-OH) 2 D 3 ) (minor) mineralization resorption 5

6 HYPOPARATHYROIDISM most commonly post thyroid surgery or congenital is characterized by the following: - serum [Ca2+] and tetany - serum [phosphate] result from urinary phosphate excretion VITAMIN D Calcium : for supplement Vitamin D : calcium level Mechanism of action: nuclear receptor Increase plasma calcium and phosphate Indication: hypocalcemia- rickets, hypoparathyroidism, osteomalacia SE: hypercalcemia Parathyroid hormone analog 6

7 PARATHYROID HORMONE (PTH) Mechanism: binding to cell membrane receptors, increased camp and increased Ca 2+ concentration Peptide: only parenteral Rx of hypocalcemia- vitamin D and calcium (safer) -severe osteoporosis in postmenopausal women parathyroid tumor (adenoma) or hyperplasia p : most common release PTH without regulation hypercalcemia, kidney stones, decalcification of bone SECONDARY HYPERPARATHYROIDISM chronic kidney diseases 1 -hydroxylase active form 1,25 dihydroxyvitamin D 3 (calcitriol) calcium feed back mechanism PTH Bone resorption osteomalacia osteitis fibrosa cystica binding with calcium-sensing receptor at chief cell of parathyroid gland receptor sensitivity to calcium negative feedback synthesis and secretion of PTH from parathyroid gland 7

8 secondary hyperparathyroidism in chronic kidney disease Hypercalcemia associated with parathyroid cancer (primary hyperparathyroidism) hypocalcemia hypophosphatemia Nausea, vomiting, dizziness VITAMIN D (CALCITRIOL) calcium and phosphate absorption from small intestine Inhibit renal calcium excretion blood calcium level negative feed back inhibit PTH secretion calcitriol, paricalcitol และ doxercalciferol Use for hyperparathyroidism in chronic kidney disease Side effects: increase blood calcium or phosphate level 8

9 CALCITONIN Opposite effects of PTH Decrease bone resorption by osteoclasts Indication: - hypercalcemia Human and salmon preparation SE: flushing, nausea, diarrhea 9

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