Toxic goitre

management of primary thyrotoxicosis

1. TOXIC GOITRE Abhilash Cheriyan

2. Thyrotoxicosis – state of increased circulating thyroid hormones irrespective of the source. Hyperthyroidism – origin of surplus hormone from increased production from thyroid gland

3. Causes of hyperthyroidism Graves disease TMNG Toxic adenoma Thyroiditis Subacute Lymphocytic Drug induced. Iodine induced Amiodarone induced. Thyrotoxicosis factitia

4. Graves disease TSH receptor activating antibody. More common in women. M:F = 7 to 10 : 1

5. Clinical presentation

6. Infiltrative ophthalmopathy TRAb – TSH receptor antibodies binds to TSH receptor antigen  T cell responsecytokinesFibroblastsGAG deposition. Seen in 20-40% patients with graves. Only severe cases need treatment.3-5% Rx options – Glucocorticoids, Orbital RT, Orbital decompressive surgery . Upto 10% are euthyroid.

7. Dermatological findings. LOCALISED DERMAL MYXEDEMA – 0.5-4.3% Always with pre-existing ophthalmopathy. 13% of patients develop myxedema. Usually pretibial. – in areas that undergo trauma, dependent areas Diffuse non pitting – 43% Plaque form – 27% Nodular myxedema – 18% Elephantiasic – 5% Rx- topical glucocorticoids for severe forms, compressive bandaging.

8. Thyroid acropachy 0.1-1 % Consists of- Digital clubbing, soft tissue swelling of hands and feet Periosteal bone formation Almost always occurs in patients with myxedema and ophthalmopathy.

9. Toxic nodular goitre Second most common cause for thyrotoxicosis. From a long standing MNG Prevalence increased with iodine insufficiency. Presents in older than 50 years. In case of MNG Solitary toxic adenoma – 3 rd to 4 th decades In 60% -TSH receptor gene – somatic mutations  activation and upregulation of cAMP .

10. Clinical presentation Usually thyrotoxicosis is mild. Often presents with CVS manifestations. ⬆T4 and T3 , ⬇TSH. RAI uptake – heterogeneous pattern with focal areas of increased uptake.

11. Lab investigations TSH T4, T3 TRAb (70-100% of Graves), TPO( 90-100 % of Hashimotos, 75% Graves) , ATG(70% Hashimotos, 30% Graves). T4 to T3 ratio – T3 toxicosis T3/T4>20 - Graves and TMNG T3/T4<20 – thyroditis, exogenous T4

12. Nuclear medicine imaging Graves – homogenous uptake TMNG- heterogeneous pattern with hyperfunctioning nodules and suppressed background.

13. Thyroid USG To identify toxic nodules and goitre. Doppler flow assessment – to differentiate between hypermetabolic/destructive

14. Management of hyperthyroidism in toxic goitres Antithyroid drugs. Beta adrenergic drugs.

15. Thionamides. imidazoles .( methimazole , carbimazole ) and thiouracil ( propylthiouracil ) Inhibition of organification of thyroid hormone. Inhibitory effect on immune system – Reduces ICAM1 and IL2 and HLA class 2 expression. Induces apoptosis in intrathyroidal lymphocytes. Use of high dose thionamides with thyroid replacement to recommended currently. PTU has shorter half life 1-2 hrs compared Methimazole once daily dose is the proffered drug. Dosage – MMI 15-30mg/d, PTU – 300mg/d in 3 divided doses.

16. Adverse effects of thionamides Abnormal taste, pruritus, arthralgia, urticaria . Cutaneous symptoms managed with antihistamines given along with therapy. Agranulocytosis - usually occurs in 1 st three months. 0.2-0.5% especially with more than >30mg of MMI Monitoring counts not recommended. Hepatotoxicity 0.1-0.2% In pregnancy – crosses placenta. PTU safer than MMI

17. Beta blockers For cardiovascular and hyperadrenergic manifestations. 1 st used in 1966. Propranolol most commonly used. More cardiac b adrenergic receptors and higher metabolism in thyrotoxicosis. Large doses of more than 160mg/d reduce T3 levels by 30% Other options – atenolol(50-100mg/d), Metoprolol (100-200mg/d) and nadolol (40-80mg/d)

18. Inorganic iodine In severe thyrotoxicosis by Wolff- chaikoff effect Blocks release of hormone. Decrease iodide transport. Prevents oxidation Thionamides administered along with iodine 1 hour prior to iodine. SSKI/ Lugols 5 drops of lugols /day( 20 drops/ml – 8mg/drop) 1 drop of SSKI/day(20 drops/mL – 38mg/drop) Iodinated contrast agents- not used any more.

19. Potassium perchlorate 2 nd line treatment Rare risk of aplastic anemia. Best used as a bridge to definitive ablative therapy with RAI/thyroidectomy.

20. Lithium Used in combination with MMI/PTU Reduces hormone secretion Inhibits coupling of iodotyrosine residues. Serum lithium maintained<1mEq/L Cholestyramine Anion exchange resin. Reduces absorption from enterohepatic circulation. Can be used along with thionamides.

21. Radioactive iodine side effects- permanent hypothyroidism, radiation thyroiditis, gastritis, sialadenitis . May increase risk of secondary malignancies. Goal is to render patient hypothyroid.. Dose depends on- gland size and radioiodine uptake. Minor risk of exacerbation of thyrotoxicosis – ?role of pretreatment with MMI reduces risk but discontinue 3-5 days prior Hypothyroidism takes 2-3 months- continue thionamides. Retreatment required if not hypothyroid in 6 months.

22. Graves disease. Antithyroid drugs, beta blockers euthyroidRIA /surgery For remission methimazole 5-10mg/day12-18 months of Rxtaper and stop  close follow up. 50-60% recurRIA /surgery For ophtalmopathy –? IV/oral glucocorticoids Post RIA – prednisolone for ophthalmopathy Smokers have poorer outcomes.

23. Toxic nodular goitre/adenoma Antithyroid drugs for euthyroid Almost certain to recur after cessation of antithyroid drugs. Definitive option – RIA/Surgery Role of RIA – larger doses needed. 15-30mCi Recurrence rate of RIA – 20%  repeat RIA/surgery

24. General indications for surgery in preference to radioactive iodine for the treatment of hyperthyroidism attributable to Graves’ disease or toxic thyroid nodule(s) Absolute indications Suspicious or biopsy-proven malignant nodules Comorbidity also requiring surgery ( eg , hyperparathyroidism) Inability to use radioactive iodine ablation Pregnancy or lactation Children<16 years of age Severe intolerance to antithyroid medication Large compressive/obstructive goiter Relative indications Severe Graves’ ophthalmopathy Poorly controlled Graves’ disease requiring definitive treatment Patients desiring pregnancy within 6 to 12 months of treatment Patients unable to continue close follow-up Patients incompletely treated by initial attempt at radioactive iodine ablation Adapted from Grodski S, Stalberg P, Robinson BG, et al. Surgery versus radioiodine therapy as definitive management for Graves’ disease: the role of patient preference. Thyroid 2007;17(2 ): 158

25. Pregnancy PTU antithyroid DOC. methimazole in 1 st trimester causes a scalp defect known as aplasia cutis choanal and esophageal atresia facial dysmorphisms in newborns May spontaneously resolve in 3 rd trimester. If surgery indicated – 2 nd trimester.