Management of Hyperthyroidism

Tuesday, 09 November 2010 08:13

Prof. K. P. Paulose S.U.T. Hospital, Trivandrum

Definition: Hyperthyroidism represents a clinical state produced by the hypersecretion of thyroid hormones (T3 and T4) resulting in a sustained rise in the plasma level. (The normal values of circulating T3 is 0.52.5 ng/ml and T4 is 40120 ng/ml. These values vary with laboratories). The common aetiological factors are: 1. Graves Disease (Toxic Diffuse Goitre) 80% 2. Toxic nodular goitre (single/multiple) 5% 3. Thyroiditis (subacute thyroiditis, chronic lymphocytic thyroiditis, post partum thyroiditis) 4. Factitious hyperthyroidism (ingestion of T4, T3, Iodides, Amiodarone) 5. Vesicular mole/choriocarcinoma or hyperemesis gravidarum 6. Follicular Carcinoma with widespread metastasis 7. Struma ovarii 8. Hyperpituitaric hyperthyroidism (Rare) Autonomous single hot nodules presenting with hyperthyroidism are rare and can be diagnosed only by radioisotope scanning and this is usually associated with T3 toxicosis. Mechanism of Hyperthyroidism: The causes of hyperthyroidism in the above mentioned conditions are given in Table 1. Although many types of immunoglobulin are found in excess in case of Graves' disease, all can be included under the category thyroid stimulating immunoglobulins, (TSIg) which is responsible for the excess synthesis of T3/T4. Treatment of Hyperthyroidism: 1. Graves' Disease: The treatment is directed solely towards controlling the excess T4/T3 secretion, the gland is destroyed in part or in toto by surgery or radiation or the pathways of hormone synthesis is interrupted by drugs. The orbital, integumentary or skeletal manifestations of the disease may not be influenced by any of this treatment. A. Drugs 1. Ion Inhibitors - Potassium perchlorate, Potassium thiocyanate - By competitive inhibition, they prevent the uptake of iodine by the thyroid gland - not used now. 2. Organic antithyroid drugs: a) Thioamides: 1) Propylthiouracil, Methylthiouracil, Methimazole, Carbimazole they inhibit thyroid peroxidase enzyme. PTU dose to start with is up to 600 mg/day. The active metabolite of carbimazole is methimazole. Dose to start with is 40/60 mg daily as a single/multiple dose. b) Other drugs: Lithium carbonate, Org. Iodides, beta-blockers and steroids. Radio-opaque dyes (Org. Iodides) like Orograffin (Na. Ipodate) or Telepaque (Iopanoic acid) can be given IV in emergencies like 'thyroid storm' 1 g/day. These dyes also suppress the conversion of T4 to T3. Inorganic iodides Saturated solution of Potassium iodide (250 mg bd) or Lugol's iodine can be given orally or sodium iodide intravenously 1 g/day. Long term therapy with iodides is not

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Management of Hyperthyroidism
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effective, since the effect disappears within 1014 days. Steroids like dexamethasone which suppresses the peripheral conversion of T4 to T3 and secretion of T4 and T3 can also be used. Response to antithyroid drugs: If treatment is prolonged, for a period of 2 years, the remission rate is about 50%. The dose can be tapered off once the person becomes euthyroid. Hypothyroidism is also reported after drug treatment. Side effects of Drugs: (Thioamides) 1.Fever, rash, joint pains: 5% 2.Agranulocytosis: 0.2 0.5%, very rare. Initial Leucopenia is common in Graves' disease (immune neutropenia) due to Thyroid Stimulating Immunoglobulin interacting with TSH receptors in granulocytes. Beta-blockers in hyperthyroidism Beta-blockers alleviate the sympathomimetic symptoms very rapidly and the dose of propranolol is up to 240 mg/day. Beta-blockers also block T4 to T3 conversion. The contraindications are bronchial asthma and cardiac failure. Beta-blockers are given with antithyroid drugs and can be withdrawn after 34 weeks, once the sympathomimetic symptoms subside. Beta-blockers is the choice of treatment in transient hyperthyroidism present in conditions like subacute thyroiditis, silent thyroiditis and postpartum thyroiditis. Antithyroid drugs may be ineffective in these conditions since hyperthyroidism here is due to increased release of thyroxine rather than due to increased synthesis. B. Radioactive Iodine I131 (half life 8 days), is used in the treatment of Graves' disease. In Western countries radioactive iodine is the treatment of choice for Graves' Disease irrespective of the age of the patient excluding the expectant mother. Principle of I131 treatment: I131 emits 2 types of radiation, the Beta and Gamma. The Beta radiation from I131 concentrated in the thyroid gland will suppress the excess activity of thyroid follicular cells and thus produce euthyroidism. Dose: Many methods to calculate the dose are in vogue, however an arbitrary dose of 4-6 MCi is given orally by many. Higher the dose, faster is the response, but more of hypothyroidism. The remission rate is up to 98% with larger doses of I131 (more than 1015 MCi) and there is also reduction in the size of the thyroid gland. Antithyroid drugs has to be stopped 23 days prior to iodine administration and can be restarted after 34 days. Put the patient on Beta-blockers (sotalol or propranolol) to get immediate symptomatic relief and then refer to iodine therapy. The incidence of hypothyroidism after low dose of I131 (45 MCi) is also high in later years (60% after 15 years). Radiation thyroiditis, sialadenitis, dryness of mouth are some of the common side effects of iodine treatment. Thyroid strom has also been reported after radioactive iodine treatment. C. Surgery Subtotal thyroidectomy is the surgery of choice. Indications: 1.Large Goitre - Nodular/Diffuse 2.Goitre with pressure symptoms 3. Pregnancy 4.Coexistent hyperparathyroidism.

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The common post surgical complications are: 1.Hypoparathyroidism (1%) 2. Recurrent laryngeal nerve paralysis (1%) 3. Recurrence of the disease (10%) and 4. Hypothyroidism (40% after 10 years). The incidence of hypothyroidism after surgery is about 10% during the first year, then about 2% per year. The overall incidence of hypothyroidism after 1015 year is less with surgery as compared to radioactive iodine. Hyperthyroidism and Pregnancy The severity of hyperthyroidism falls during pregnancy and the association of Graves' disease with pregnancy is very low one in 1,000 pregnancies. There is increased risk of prematurity, foetal loss and malformations in Graves' associated with pregnancy. Since there is transplacental passage of all antithyroid drugs, neonatal hypothyroidism and goitre can occur and so keep the dose of the antithyroid drugs as low as possible. The preferred treatment in early pregnancy (up to 6 months) is surgery. After that period PTU in the lowest dose possible is recommended. PTU is safer in pregnancy than carbimazole. Aplasia cutis of the scalp in neonates can occur with carbimazole, but not with PTU. Beta-blockers can also pass through placenta resulting in bradycardia, hypoglycemia and growth retardation in neonates. If adequately treated, the outcome of pregnancy is normal in about 8090% of cases. Neonatal hyperthyroidism is also possible due to transplacental transfer of thyroid stimulating immunoglobulins. Gestational transient hyperthyroidism can occur as in hyperemesis at the end of the first trimester or may be associated with vesicular mole or choriocarcinoma. Management of Exophthalmos There is no specific treatment for this condition. During treatment of Graves', the exophthalmos may subside in some, but it remains unchanged or worsens in others. a) Irritation and watering of the eyes are benefited by eye-drops containing methyl cellulose, steroids or 5% guanethidine. Use of sunglasses with side shields helps to avoid irritation by sun-rays. Botulinum toxin to paralyse selected extra ocular muscles has also been tried to avoid diplopia. b) Malignant exophthalmos is treated by systemic prednisolone 6090 mg/day to prevent blindness. Lateral tarsorraphy is advocated to prevent exposure keratitis. If no improvement with high dose of steroids, orbital decompression is undertaken especially when the vision is threatened or papilloedema develops. Irradiation of retro-orbital tissues may arrest the progress of exophthalmos. Long term use of octreotide by daily S/C injection is beneficial in exophthalmos. Plasmapheresis has also been attempted as a temporary measure with limited success. Thyroid Storm Thyroid Storm (Thyroid crisis) is a grave condition of decompensated thyrotoxicosis. The patient has tachycardia, fever, agitation, restlessness, nausea, vomiting and diarrhoea. Intercurrent illnesses such as gastroenteritis, pneumonia or emergency surgery precipitates thyroid storm in uncontrolled hyperthyroidism. Therapy includes maintenance of fluids and electrolytes, treatment of underlying infection, and maintaining the blood pressure. Specific treatment directed against hyperthyroidism includes: 1. Large doses of antithyroid drugs (PTU 600 mg) or carbimazol 60 mg st. orally or through intra-gastric tube and half of this dose repeated every 6 hrly. 2.Sodium Ipodate (orograffin) IV or Sodium Iodide IV (1 gm) or sat. solution of KI 500 mg/st.

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orally and continued for 710 days. 3. Propranolol in large doses 80 mg 6th hrly orally or small doses (1 mg 10 mg) IV to reduce heart rate. One should monitor heart during IV beta-blocker therapy. 4. Dexamethasone 48 mg/tds and repeated. 5. In institutions where facilities are available, plasmapheresis is recommended with very favourable outcome.

Table I

Disease Mechanism 1. Graves' Disease Excess stimulation of thyroid by thyroid stimulating Immunoglobulins (TSIg) 2. Hydatiform mole/chorio Excess stimulation by carcinoma/Hyperemesis human chorionic gonadotrophins Gravidarium 3. Thyroiditis Excess release of T3/T4 into circulation 4. Factitious Thyrotoxicosis Excess ingestion of T3/T4 5. Autonomous hot nodule, Autonomous unrestricted struma ovarii, multinodular goitre hormone production

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