This document discusses various causes of hyperthyroidism including Graves' disease, toxic multinodular goiter, and toxic adenoma. It describes the clinical presentation, investigations, and management of these conditions. Management may include antithyroid medications, beta blockers, radioactive iodine, or surgery depending on the severity and specific cause of the hyperthyroidism. Pregnancy poses additional considerations in treatment due to risks of medications to the fetus.

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. Toxic goitre
Diffuse toxic
goitre (Graves
disease)
Toxic
multinodular
goitre
Toxic nodule Thyroiditis

5. 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

6. Clinical presentation
Thyroid gland
findings
• Goitre
• Bruit
Ophthalmic
findings
• Proptosis
• Ophthalmoplegia
• Conjunctival
irritation.
Dermatologic
findings
• Dermal
myxedema
• Hair loss

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

13. 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

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

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

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

17. 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.

18. 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

19. 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)

20. 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.

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

22. 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.

23. 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.

24. 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.

25. 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

26. 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

27. 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.