THYROID& ANTITHYROID

Thyroid Gland One of the largest endocrine glands One of the largest endocrine glands Secretes three hormones essential for proper regulation of metabolism Secretes three hormones essential for proper regulation of metabolism –Thyroxine (T 4 ) –Triiodothyronine (T 3 ) –Calcitonin Located near the parathyroid gland Located near the parathyroid gland Involved in many bodily processes, growth, body temperature regulation, cardiovascular, endocrine & neuromuscular functions. Involved in many bodily processes, growth, body temperature regulation, cardiovascular, endocrine & neuromuscular functions.

Iode from diet is responsible for the synthesis thyroglobuline Iode from diet is responsible for the synthesis thyroglobuline Hypothalamus secretes TSH that stimulates the thyroid to break down thyroglobulin into T3( & T4( and is released into the circulation Hypothalamus secretes TSH that stimulates the thyroid to break down thyroglobulin into T3(iodine 59%) & T4(iodine 65%) and is released into the circulation

Tahapan sintesa & sekresi : 1. 1.uptake yodida 2. 2.oksidasi & yodinasi 3. 3.pembentukan T4 & T3 dari yodotirosin 4. 4.sekresi hormon tiroid 5. 5.konversi T4  T3 di jar. perifer  enz.5-deyodinase  dihambat oleh : malnutrisi, hipoglikemi, kortikosteroid,  bloker, PTU, defisiensi Se dll.

tyroglobulin I -  I - peroxidase I * MIT, DIT, T3, T4 transport proteolisis I - tyrMIT, DIT exocytosis T4, T3 (ikt.protein) darah Jar. perifer : T4, T3 T3 Kel.tiroid

Mekanisme Kerja : Melalui reseptor tiroid di dlm sel  regulasi gen spesifik  pertumbuhan & metabolisme 1. 1.Tiroid diperlukan unt.tumbuh kembang termsk CNS  hipotiroid (hamil)  kretinisme 2. 2.Efek kalorigenik : T4 meningkatkan metabolisme, katabolisme, pembentukan kalori , termogenesis, vasodilatasi perifer, curah jantug  CVS takhikardia, CO , SV , hipertropi

Hypothyroidism: Deficiency in Thyroid Hormones Primary: abnormality in the thyroid gland itself. Most common cause is hashimoto’s thyroiditis. Primary: abnormality in the thyroid gland itself. Most common cause is hashimoto’s thyroiditis. Secondary: results when the pituitary gland is dysfunctional and does not secrete TSH Secondary: results when the pituitary gland is dysfunctional and does not secrete TSH

Thyroid abnormalities Cretinism: Hyposecretion of thyroid hormone during youth. Low metabolic rate, retarded growth and sexual development, possibly mental retardation Myxedema: Hyposecretion of thyroid hormone as an adult. Decreased metabolic rate, loss of mental and physical stamina, weight gain, loss of hair, firm edema, yellow dullness of the skin Goiter: Enlargement of the thyroid gland. Results from overstimulation by elevated levels of TSH. TSH is elevated because there is little or no thyroid hormone in circulation Goiter: Enlargement of the thyroid gland. Results from overstimulation by elevated levels of TSH. TSH is elevated because there is little or no thyroid hormone in circulation

Hypothyroidism Common symptoms Common symptoms –Thickened skin –Hair loss –Constipation –Lethargy –Anorexia

Thyroid Preparations levothyroxine * most common levothyroxine * most common –Synthetic thyroid hormone T 4 liothyronine liothyronine –Synthetic thyroid hormone T 3

Mechanism of Action Thyroid preparations are given to replace what the thyroid gland cannot produce to achieve normal thyroid levels. Thyroid preparations are given to replace what the thyroid gland cannot produce to achieve normal thyroid levels. Thyroid drugs work the same way as thyroid hormones Thyroid drugs work the same way as thyroid hormones

Indications To treat all three forms of hypothyroidism To treat all three forms of hypothyroidism levothyroxine is the preferred agent because its hormonal content is standardized; therefore, its effect is predictable levothyroxine is the preferred agent because its hormonal content is standardized; therefore, its effect is predictable Also used for thyroid replacement in clients whose thyroid glands have been surgically removed or destroyed by radioactive iodine in the treatment of thyroid cancer or hyperthyroidism

Side Effects Cardiac dysrhythmia is the most significant adverse effect Cardiac dysrhythmia is the most significant adverse effect May also cause: May also cause: –Tachycardia, palpitations, angina, hypertension, insomnia, tremors, headache, anxiety, nausea, diarrhea, menstrual irregularities, weight loss, sweating, heat intolerance, others

Hyperthyroidism Excessive Thyroid Hormones: free T3 & T4 Caused by several diseases Caused by several diseases –Graves’ disease –Toxic nodular disease –Multinodular disease –Thyroid storm –Thyroid cancer –Pituitary hormones

Hyperthyroidism Affects multiple body systems, resulting in an overall increase in metabolism Affects multiple body systems, resulting in an overall increase in metabolism –Wt loss –Diarrhea– Fatigue –Flushing– Palpitations –Increased appetite– Nervousness –Muscle weakness– Heat intolerance –Sleep disorders– Irritability –Altered menstrual flow

Antithyroid drugs 1. 1.Prevent hormone thyroid synthesis 2. 2.Prevent yodide ion transport/anion inhibitors 3. 3.Yodides  prevent synthesis & release thyroid hormone 4. 4.Radioactive iodine  bloker Treatment of Hyperthyroidism Surgery to remove all or part of the thyroid gland Surgery to remove all or part of the thyroid gland

tyroglobulin I -  I - peroxidase I * MIT, DIT, T3, T4 transport proteolisis I - tyr MIT, DIT exocytosis T4, T3 (ikt.protein) darah Jar. perifer : T4, T3 T3 Kel.tiroid PTU SCN ClO 4 Yod  bloker

1. 1.Prevent hormone thyroid synthesis contoh obat : PTU (propilthiourasil), Metimazol, Karbimazol, Metiltiourasil Farmakokinetik : per oral, distribusi slrh tubuh, ekskresi mel. urin & ASI masa kerja pendek  8 jam (PTU) Efek samping : demam, purpura, agranulositosis, ikterus, goiter pada fetus (dose dependent) Sering digunakan bersama yodium untuk mengurangi vaskularisasi pra operasi

2. Prevent iodide ion transport Drug exp : thiocyanate (SCN - ), perchlorate(ClO4 - ). Effect : block uptake iodide  prevent thyroid functions 3. Yodide Drug exp : natrium yodida, kalium yodida (lugol solution) Effect : inhibit release & organification thyroid horm decrease the size and vascularity of gland 4. Radioactive iodine Drug exp. : I 131 Effect : I works by destroying the thyroid gland Effect : I 131 works by destroying the thyroid gland 5.  BLOKER Prevent yodisation T4, clinical improvement

Tugas : Buat ringkasan tentang hormon Paratiroid dan regulasi calcium Sifat kimia Sintesa dan sekresi Fungsi fisiologis Regulasi sekresi Efek pada organ : tulang dan ginjal