Thyroid, antithyroid, parathyroid & Calcium metabolism. Suharti K Suherman Dept. of Pharmacology & Therapeutic Medical Faculty, Univ.

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1 Thyroid, antithyroid, parathyroid & Calcium metabolism Suharti K Suherman Dept. of Pharmacology & Therapeutic Medical Faculty, Univ. of Indonesia

2 Thyroid secreted by thyroid gland source of 2 different type of hormones : a. tetraiodothyronine (T 4 ) & triidothyronine (T 3 ) essential for normal growth & b. calcitonin secreted by parafollicular cells Synthesis unique & complex - TH are synthesized & stored as AA residues of thyroglobulin = a protein component of thyroid follicular colloid

3 Thyroid H the only hormone that contains iodine 2 important functions : * in developing phase determinants of normal development espsl CNS devepl. * in adult it maintains metabolic homeostasis affecting the function of all organ

5 Steps of thyroid h synthesis & secretion 1 - uptake or active transport of I - by the gland 2 - oxidation of iodide & iodination of tyrosyl residues in thyroglobulin 3 - coupling of iodotyrosine molecules within thyroglobulin to form T4 & T3 4 - proteolysis of thyroglobulin, with release of free iodothyronines & iodotyrosines into the circulation 5 deiodination of iodotyrosines within the thyroid cell 6 intrathyroidal conversion of T 4 to T 3 as well as in peripheral tissue

6 ** thyroid H in the circulation is bound in thyroxine binding globulin (TBG) major carrier of TH T4 is also bound to TB prealbumin a small number is bound to albumin or free **degradation & excretion : eliminated slowly from the body t ½ 6 8 days hyperthyroidism shortened to 3 4days hypothyroidis 9 10days pregnancy binding to TBG retarded clearence ** metabolism liver

7 Factors that alter binding of Thyroid to TBG Binding Binding estrogen glucocort clofibrate androgen 5 fluorouracil salicylates tamoxifen mefenanic acid SERM phenytoin, carbarmazepin

8 Treatment Hypothyroidism levothyroxine Na (L-T4) tablet & as lyophilized powder for inj, replacement dose mg/d with a mean of about mg/d; Liothyronine Na (L-T3) tab & injectable form mixture of L-T4 & L-T3 = Liotrix

9 L-T4 prefer for thyroid replacement longer duration of action, 50 80% of the dose is absorbed blood level is easily monitored by FT4 & TSH serum level T1/2 7 days once daily Side effects : allergic reactions, signs of hyperthyroidis

10 Drugs interactions: # cholestyramin,iron,calcium,al (OH)3 & soy product interfere L-T4 absorption # phenytoin, carbamezepin & rifampin biliary excretion of L-T4 often necessary the dose # pregnant woman/oral contracept the dose of levothyroxine need to be due to serum TBG induced by estrogen

11 Hyperthyroidism antithyroid propylthiouracil ( PTU), methimazole & carbimazol (a carbethoxy derivative of methimazole it inhibits thyroglobulin to form T4 & T3 within the thyroid gland PTU, but not methimazole, block peripheral conversion T4 to T3

12 PTU Methim plasma prot binding %...nil plasma t1/2 75 min..4 6 hrs concentrated in thyroid yes.yes metab in severe liver disease..normal. kidney disease..normal.normal * dosing frequency..1-4 x/d..1 2 x/d transplacental/ breast milk low.

13 Side effects Skin rash ( 3% & 7%) Agranulocytosis ( 0.44 & 0.12% )

14 Parathyroid & vit D a polypeptide hormone, regulates plasma Ca ++ by affecting boneformation & resorption, renal Ca ++ excretion/ reabsorption, & calcitriol synthesis ( indirectly regulates GI calcium absorption importance role in calcium metabolism secreted by parathyroid gland Ca ++ plasma = the most powerful regulator for its secretion

15 Ca ++ plasma is low PTH secretion, if the hypocalcemia is sustained hypertrophy & hyperplasia of the gland

16 Fig-1.Whole body daily turnover of calcium

17 Fig-2.Calcium homeostasis & its regulation by PTH & 1.25-dihydroxyvitamin D.

18 effects on bone PTH bone resorption, Ca ++ delivery to the extracellular fluid the cellular terget for PTH is the osteoblast it recruits osteoclast precursors to form new bone remodeling units (fig-3) Effects on kidney

19 O ther fa c tor to bone s treng th : bone turn over Fig-3 Bone remodeling sequence in healthy subjects

21 Calcitonin hormone produced by parafollicular C cells A single chain peptide hormone IM / nasal spray Postmenopausal oeteoporosis calcitonin inhibit osteoclast activity in bone resorption osteoklast BMD = Bone Mineral Density)

22 enough intake Calcium cukup & vitamin D Preparations : synthetic salmon calcitonin nasal spray 50 IU 2x/ day or injection ampul 50 IU 1 x / 2 days Adverse reactions : nausea, flushing, dose-dependent

23 Calcitriol active metabolite of vit. D3 synthesized by the kidney from its precursor 25-OH cholecalciferol Its productions per day ± 0,5 1,0 µg in pregnancy during bone development Normal fuction GI absorption of Ca ++ & regulates bone mineralisation

24 Osteoporotic postmenopausal woman calcitriol bone resorption cegah hilangnya massa jaringan tulang, tetapi pembentukan tulang tidak berubah Dosis : 0,25 ug 1 x / 2 x / hari dapat menyebabkan hiperkalsemia & hiperkalsiuria

25 OK dosis awal dimulai 0.25mg/h -- setelah itu dapat di 0.5 mg/h monitor kadar Ca++ Adverse reactions : hypersens

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

25/10/56. Hypothyroidism Myxedema in adults Cretinism congenital deficiency of thyroid hormone Hashimoto thyroiditis. Simple goiter (nontoxic goiter) THERAPEUTIC USES OF THYROID HORMONE Supeecha Wittayalertpunya Wannarasmi Ketchart Nov 2013 Hyperthyroidism (Thyrotoxicosis) Grave s disease (diffuse toxic goiter) Toxic uninodular & Toxic multinodular