Thyroid Gland

Introduction

Thyroid Gland is Member of the Endocrine System and Secretes three hormones triiodothyronine (T3) ; 59% iodine ,tetraiodothyronine (T4; also known as thyroxine); 65% iodine& calcitonin. Its Located in neck adjacent to the 5th cervical vertebra (C5) and Composed of epithelial cells which specialize in the absorption of iodine and, of course, secretion of thyroid hormones. Follicles surround a protein core, the colloid, where thyroglobulin, a substrate in thyroid hormone

synthesis, and thyroid hormones are stored.

Regulation of thyroid hormone as discus in hormone

Steps in Biosynthesis

1. Uptake of iodide2. Oxidation of iodide (peroxidase)

and iodination and coupling of tyrosine(Iodide Organification)

3. Formation of thyroxine (T4) and triiodothyronine (T3) from iodotyrosine(Coupling ).

- Monoiodotyrosine MIT + Diiodotyrosine DIT = T3 (Tri-iodothyronine)

- Diiodotyrosine DIT + Diiodotyrosine DIT = T4 (Thyroxine)4. Secretion of thyroid hormones (proteolytic enzymes).5. Regulation by thyroid stimulating hormone (TSH), T4, T3.

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Normal Actions of thyroid hormones

1- Regulation of growth and brain development- The absence of thyroid hormone in early life --- results in irreversible mental

retardation and cretinism.- The absence of thyroid hormone in adult people--- results in ---Myxoedema.

2- Necessary for thermogenesis3- Increase in the metabolism of carbohydrates, Fate and proteins.4- Increase heart rate and cardiac output.

Thyroid drugs

1- levothyroxine (L-T4) L-Thyroxine 25µg-200µg (1-1.7µg/kg/d)2- liothyronine (T3) 5µg-75µg /d3- liotrix (T4 plus T3= 4:1) 60-180 mg4- Desiccated thyroid 60-180 mg

Mechanism of action

Interaction of T3 with the T3 receptor

Clinical use As Replacement therapy in deficiency states

1- Cretinism2- Adult Hypothyroidism

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3- Myxoedema coma

4- Nontoxic goiter 5- Thyroid nodule 6- Papillary carcinoma of thyroid7- Empirical uses.

Adverse reactions

1- Nervousness, Hypertension2- Shortness of breath, Vomiting and diarrhea, Increased sensitivity to heat.3- Impaired reproductive function.4- Hyperthyroidism especially in the elderly.

Anti-thyroid (Thyroid Inhibitors)

Classification

1- Inhibit Hormone synthesis (Antithyroid Drugs): Propylthiouracil, Carbimazole, Methimazole – also called Thioamides (Thiourea derivatives).

2- Inhibit iodide trapping(Ionic Inhibitors): Thiocyanates (-SCN), Perchlorates (-

ClO4), Nitrates (-NO3). rarely used due to its association with aplastic anemia.

3- Inhibits Hormone Production and release: Iodine, Iodides of Na and K, Organic Iodide.

4- Destroy Thyroid tissue: Radioactive Iodine (131I,125 I,123 I).

Thioamides

These drugs have no effects on the thyroglobulin already stored in the gland. Therefore the clinical effects of thioamides may take several weeks to show until thyroglobulin stores depleted .

Mechanism

1- Inhibiting the formation of thyroid hormones by interfering with iodination: inhibiting peroxidation, then the iodination and coupling

2- Inhibiting peripheral deiodination of T4: T4 T3 (propylthiouracil

Therapeutic applications

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1. Hyperthyroidism2. Supplementary treatment of thyrotoxic crisis 3. Preparation for thyroid surgery.

Adverse effects

1. Skin rashes, fever, enlargement of lymph glands

2. Agranulocytosis (in 0.3 % of patients) -infrequent but most dangerous

3. Hepatic abnormalities

4. These drugs can cross the placenta and cause fetal hypothyroidism.

Radioactive Iodine ( 131 I, 125 I, 123 I).

131I is the only isotope for treatment of thyrotoxicosis. Its therapeutic effect depends on emission of β rays with an effective half-life of 5 days & a penetration range of 0.4-2 mm. Cytotoxic effect on gland is delayed for 1-2 month and maximum effect reached in 4 months.

Adverse effects1. permanent hypothyroidism2. potential for genetic damage3. may precipitate thyroid crisis

Iodine and iodidesmajor anti-thyroids before the introduction of thioamides (1950s)

preparations:1. strong iodine solution (Lugol’s): 5% iodine and 10% potassium iodide.2. potassium iodide3. iodone

Mechanism Of Action:- acutely blocks release of thyroid hormone from the gland by inhibiting thyroglobulin

proteolysis- inhibit iodide organification

Uses:1. useful in thyroid storms: 2-7 days2. 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.

Beta Blockers- Drugs: Propranolol, Metoprolol, Atenolol- Mechanism of Action

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Membrane-stabilizing action: inhibits T4 to T3 Indications: Grave’s, Thyroid storm

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