Thyroid hormones BDS May 2013

Dr.U.P.Rathnakar
MD.DIH.PGDHM
1

T4&T3 Actions
Growth&development Metabolism Calorigenesis CVS Nervous system Sk.Muscles GIT Blood Reproduction

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Thyroid hormones Uses

Cretinism [Congenital Hypothyroidism] Adult hypothyroidism Myxoedema coma
Non-toxic goiter Thyroid nodule Papillary carcinoma of thyroid Non-specific uses
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Preparations L-Thyroxine [T4] Liothyronine[T3] Oral & i.v

Conversion

1to5
TSH ACTIVATES
Antithyroids drugs
NIS

1 Ionic inhibitors block 2 Carbimazole Methimazole Propylthiouracil 1-2-3-5 Pendrin Iodides 6 Propranolol, Prednisolone, Propylthiouracil 131I

6 5 4

2
oxidation

3
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CLASSIFICATION
1. Inhibitors of iodide trapping (anion inhibitors):
Thiocyanates, perchlorates.

2. Thyroid hormone synthesis inhibitors

Propylthiouracil, methimazole, carbimazole. (Thioamides or thiourea derivatives)

3. Hormone release inhibitors:

Iodine, iodides of Na + and K+, organic iodide.

4. Thyroid tissue-destroying agent:

Radioactive iodine (131I).

5. Others:
Propranolol, atenolol, diltiazem, dexamethasone.
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IONIC INHIBITORS
Not used because of ADEs Monovalant anions like iodides Thiocynates: can cause liver, kidney, bone marrow and brain toxicity[cabbage, cigarette smoking] Perchlorates: produce rashes, fever, aplastic anaemia, agranulocytosis Nitrates: are weak drugs, can induce methemoglobinaemia and vascular effects 15

Antithyroid drugs
[Popylthiouracil-Methimazole-Carbimazole]

MOA Inhibit peroxidase Oxidation of Iodides-Inhibited

Iodination of tyrosine-inhibited

Coupling-Inhibited Synthesis of T3&T4 inhibited Effective only after stores of iodinated thyroglobulin depleted. Propylthiouracil inhibits [5 DI] peripheral 16 conversion of T4 to T3

Pharmacokinetic Features of Anti-thyroid Drugs

[Carbimazole is the prodrug of Methimazole

Peripheral conversion

Inhibits

No

17 [More than PTU]

Antithyroid drugs Adverse effects

Hypothyroidism and goiter -reversible G.i. intolerance
Rare but serious adverse effect- aganulocytosis (1 in 500 to 1000 cases)-periodic counts-reversible.

Rashes and joint pain.

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Antithyroid drugs Therapeutic uses

1. Definitive treatment, in Graves' disease 2. With radioactive iodine, to hasten recovery while awaiting the effects of radiation 3. To control the disorder in preparation for surgical treatment 4. Thyroid storm

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Antithyroids and Preoperative use

Pts rendered euthyroid-to reduce operative[Subtotal thyroidectormy] morbidity & mortality Others Iodides-less vascularity, less friable Dexamethasone, propranolol-7 days before
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Adjuant therapy with Antithyroid drugs

No intrinsic antithyroid activity blockers-palpitations, tremor,anxiety Propranolol or atenolol Diltiazem Dexamethasone Radiological contrast media Cholestyramine Rituximab-TSI
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Thyroid storm (thyrotoxic crisis) [Life threatening]

Propranolol, iodides, PTU, Prednisolone Propranolol 1-2 mg slow i.v. may be followed by 40-80 mg oral every 6 hours . Propylthiouracil 200-300 mg oral 6 hourly Hydrocortisone 100 mg i.v. 8 hourly followed by oral prednisolone) To tide over crisis, cover any adrenal insufficiency Diltiazem 60-720 mg BD Rehydration, anxiolylics, external cooling and antibiotics 22

Iodides
Inhibit all aspects of iodine metabolism by the thyroid gland. Acute inhibition of the synthesis of T4& T3 Wolff-Chaikoff effect Vascularity is reduced, gland firm. Thyroid constipation Symptoms reappear- Thyroid escape
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Iodides- Preparations
Lugol's solution- 5% iodine and 10% KI- 8 mg of iodine / drop
Saturated solution of potassium iodide (SSKI) al-50 mg / drop Dose -16-36 mg TID
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Iodides-ADEs
Acute
Angioedema and laryngeal. Multiple cutaneous hemorrhages may be present. Fever, arthralgia, lymph node enlargement, and eosinophilia.
Chronic- Iodism Unpleasant brassy taste and burning in the mouth and throat Coryza, sneezing, and irritation of the eyes with swelling of the eyelids Parotid and submaxillary glands -enlarged and tender, -mistaken for mumps Skin lesions are common Diaarhoea Disappear spontaneously within a few days after stopping

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Radioactive Iodine
Radioactive isotopes of Iodine-123I and 131I 123I, -emitter -in diagnostic studies 131I emits both rays and particles- used therapeutically for thyroid destruction Trapped and incorporated and deposited in the colloid of the follicles Destructive particles originate within the follicle and act almost exclusively on the parenchymal cells of the thyroid, damage to surrounding tissue. radiation passes through the tissue and can be quantified by external detection 26

Radioactive Iodine Therapeutic Uses

Advantages Safe-no mortality Not expensive No risks of surgery No hospitalization Disadvantages Long time for control Not in young CI pregnancy Radiation thyroiditis [Worsening of ophthalmopathy and hyperthyroidism] Increase shown in -cancer, including stomach, kidney, and breast
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