TOXIC GOITREAbhilash Cheriyan

• Thyrotoxicosis – state of increased circulating thyroid hormones irrespective of the source.

• Hyperthyroidism – origin of surplus hormone from increased production from thyroid gland

Causes of hyperthyroidism• Graves disease• TMNG• Toxic adenoma• Thyroiditis• Subacute• Lymphocytic• Drug induced.

• Iodine induced• Amiodarone induced.

• Thyrotoxicosis factitia

Toxic goitre

Diffuse toxic goitre (Graves

disease)

Toxic multinodular

goitreToxic nodule Thyroiditis

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

TSAb binds to the TSH receptor

Activation of adenyl-cyclase

Increased thyroid

hormone production

Clinical presentation

Thyroid gland findings• Goitre• Bruit

Ophthalmic findings• Proptosis• Ophthalmoplegia• Conjunctival

irritation.

Dermatologic findings• Dermal

myxedema• Hair loss

Infiltrative ophthalmopathy• TRAb – TSH receptor antibodies binds to TSH

receptor antigen T cell responsecytokinesFibroblastsGAG 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.

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.

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.

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 – 3rd to 4th decades• In 60% -TSH receptor gene – somatic

mutations activation and upregulation of cAMP.

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.

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

Nuclear medicine imaging• Graves – homogenous uptake• TMNG- heterogeneous pattern with hyperfunctioning

nodules and suppressed background.

Thyroid USG• To identify toxic nodules and goitre.• Doppler flow assessment – to differentiate between

hypermetabolic/destructive

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

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.

Adverse effects of thionamides• Abnormal taste, pruritus, arthralgia, urticaria.• Cutaneous symptoms managed with antihistamines given

along with therapy.

• Agranulocytosis- usually occurs in 1st 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

Beta blockers• For cardiovascular and hyperadrenergic manifestations.• 1st 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)

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.

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

RAI/thyroidectomy.

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.

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.

Graves disease.• Antithyroid drugs, beta blockerseuthyroidRIA/surgery• For remission methimazole 5-10mg/day12-18 months of

Rxtaper and stop close follow up.• 50-60% recurRIA/surgery• For ophtalmopathy –? IV/oral glucocorticoids• Post RIA – prednisolone for ophthalmopathy• Smokers have poorer outcomes.

Toxic nodular goitre/adenoma• Antithyroid drugsfor 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

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 goiterRelative 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

ablationAdapted 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

Pregnancy• PTU antithyroid DOC.• methimazole in 1st trimester causes• a scalp defect known as aplasia cutis• choanal and esophageal atresia• facial dysmorphisms in newborns

• May spontaneously resolve in 3rd trimester.• If surgery indicated – 2nd trimester.