Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

nonpregnant nonlactating adults: without mass effect or suspicion of cancer

1st line – radioactive iodine therapy (I-131)

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nonpregnant nonlactating adults: without mass effect or suspicion of cancer
1st line – 

radioactive iodine therapy (I-131)

The hyperthyroidism of toxic multinodular goiter generally does not remit spontaneously, and therefore definitive treatment is usually required.

Patient values and preferences are an important part of any therapeutic decision-making process about definitive treatment. For example, patients who choose I-131 therapy would most likely favor avoidance of issues surrounding surgery, such as anesthesia or hospitalization, and their possible complications; and hope to remain euthyroid.[13]

I-131 is a preferred treatment for most nonpregnant and nonlactating patients.

Generally either a fixed dose of I-131, a calculated dose based on goiter size, or a computed dose based on amount of radiation to be delivered is used.[1]

Antithyroid drugs, if used adjunctively, should be stopped 3 to 5 days before I-131 treatment and restarted 3 to 5 days after treatment.

I-131 may worsen thyrotoxicosis for several days due to thyroid hormone leakage.[42]

Pregnancy test in women of childbearing age is necessary prior to therapy.[1]

Use with caution in older people, especially in those with heart disease. These patients require consideration of pretreatment with antithyroid drugs and careful monitoring.

Consider – pretreatment antithyroid drugs

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nonpregnant nonlactating adults: without mass effect or suspicion of cancer
Consider – 

pretreatment antithyroid drugs

Treatment recommended for SOME patients in selected patient group

May be given prior to I-131 therapy for older patients and for those with severe symptoms or comorbidities such as heart disease. Can also be restarted if needed after I-131 therapy is given. Some controversy exists as to the necessity for pretreatment with antithyroid drugs if symptoms are controlled with beta-blockade.[13]

Should be stopped 3 to 5 days before I-131 treatment and restarted 3 to 5 days after treatment.

Serious complications include agranulocytosis (0.1% to 0.3% of patients) and liver toxicity.[3] Vasculitis can occur with propylthiouracil.[38]

Methimazole is the preferred drug due to a higher risk of hepatotoxicity with propylthiouracil. Methimazole also has the advantage of less-frequent dosing.

Primary options

methimazole: 5-60 mg/day orally given once daily or in 2-3 divided doses; doses rarely exceed 40 mg/day in practice

Secondary options

propylthiouracil: 50-400 mg/day orally given in 3 divided doses

2nd line – thyroid surgery

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nonpregnant nonlactating adults: without mass effect or suspicion of cancer
2nd line – 

thyroid surgery

The hyperthyroidism of toxic multinodular goiter generally does not remit spontaneously, and therefore definitive treatment is usually required.

Patient values and preferences are an important part of any therapeutic decision-making process about definitive treatment. For example, those choosing surgery may prefer avoidance of radioactivity; desire very rapid control of hyperthyroidism; or have a lower concern about risks of surgery or the likelihood of immediate permanent hypothyroidism.[13]

Surgery is an option for those resistant to, or who decline, radioactive iodine, or those who prefer surgery.[1]

An experienced, high-volume surgeon is recommended. Risk of complications, including recurrent laryngeal nerve damage and hypoparathyroidism, should be <2% if the surgeon is experienced.[43] Hypocalcemia due to hypoparathyroidism may be transient or permanent.

Reduction of thyroid function is immediate, although recurrent hyperthyroidism is possible and subsequent hypothyroidism is likely.

Consider – presurgical antithyroid drugs

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nonpregnant nonlactating adults: without mass effect or suspicion of cancer
Consider – 

presurgical antithyroid drugs

Treatment recommended for SOME patients in selected patient group

Given prior to surgery to normalize thyroid function, especially for older patients and for those with severe symptoms or comorbidities such as heart disease.

Serious complications include agranulocytosis (0.1% to 0.3% of patients) and liver toxicity.[3] Vasculitis can occur with propylthiouracil.[38]

Methimazole is the preferred drug due to a higher risk of hepatotoxicity with propylthiouracil. Methimazole also has the advantage of less-frequent dosing.

Primary options

methimazole: 5-60 mg/day orally given once daily or in 2-3 divided doses; doses rarely exceed 40 mg/day in practice

Secondary options

propylthiouracil: 50-400 mg/day orally given in 3 divided doses

3rd line – antithyroid drugs alone

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nonpregnant nonlactating adults: without mass effect or suspicion of cancer
3rd line – 

antithyroid drugs alone

Usually less-preferred therapy in nonpregnant patients, because remission of hyperthyroidism in patients with toxic multinodular goiter is rare.[38]

Also used when required before surgery or I-131 therapy, especially for older patients, for those with severe symptoms or comorbidities such as heart disease, or when more definitive therapies are contraindicated or refused.

Serious complications include agranulocytosis (0.1% to 0.3% of patients) and liver toxicity.[3] Vasculitis can occur with propylthiouracil.[38]

Methimazole is the preferred drug due to a higher risk of hepatotoxicity with propylthiouracil. Methimazole also has the advantage of less-frequent dosing.

Primary options

methimazole: 5-60 mg/day orally given once daily or in 2-3 divided doses; doses rarely exceed 40 mg/day in practice

Secondary options

propylthiouracil: 50-400 mg/day orally given in 3 divided doses

Consider – beta-blockers pending effects of definitive therapy

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ONGOING
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nonpregnant nonlactating adults: without mass effect or suspicion of cancer
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with moderate or severe symptoms and/or increased cardiovascular risk
Consider – 

beta-blockers pending effects of definitive therapy

Treatment recommended for SOME patients in selected patient group

Used for symptoms such as palpitations, anxiety, or tremor, or in patients with increased cardiovascular risk.[3][42] Generally recommended for older adults with symptoms or younger people with heart rate >90 bpm.[13] Should be used with caution in older people and those with heart disease.

Dose should be gradually increased until symptoms and pulse are controlled, then gradually tapered when the patient is euthyroid.[3][44]

Useful before surgery and I-131 therapy, or while waiting for antithyroid drugs to take effect.[3]

A selective beta-blocker can be used in patients who cannot tolerate propranolol.

If beta-blockers are contraindicated, an alternative is a calcium-channel blocker such as diltiazem.

Primary options

propranolol hydrochloride: 10-40 mg orally (immediate-release) four times daily, increasing if necessary until symptoms and pulse rate are controlled, usual dose is 80-160 mg/day although higher doses have been reported by some specialists

Secondary options

atenolol: 25-50 mg orally once daily, increase if necessary to 100 mg/day

mass effect or suspicion of cancer

1st line – thyroid surgery

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ONGOING
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mass effect or suspicion of cancer
1st line – 

thyroid surgery

Option for patients with large goiters that cause obstructive symptoms such as choking or dyspnea.[1][39] Surgery may also be indicated based on fine needle aspiration findings when a suspicious cold nodule occurs in a toxic multinodular goiter.[28][29] 

Surgery during pregnancy is rarely indicated and then preferably performed during the second trimester.

An experienced, high-volume surgeon is recommended. Risk of complications, including recurrent laryngeal nerve damage and hypoparathyroidism, should be <2% if the surgeon is experienced.[43] Hypocalcemia due to hypoparathyroidism may be transient or permanent.

Reduction of thyroid function is immediate, although recurrent hyperthyroidism is possible and subsequent hypothyroidism is likely.

Consider – presurgical antithyroid drugs

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ONGOING
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mass effect or suspicion of cancer
Consider – 

presurgical antithyroid drugs

Treatment recommended for SOME patients in selected patient group

These normalize thyroid function prior to surgery.

Serious complications include agranulocytosis (0.1% to 0.3% of patients) and liver toxicity.[3] Vasculitis can occur with propylthiouracil.[38]

Birth defects have been associated with both methimazole and propylthiouracil when used during the first trimester of pregnancy, although the defects associated with methimazole tend to be more severe.

Propylthiouracil does, however, have more frequent dosing compared with methimazole, and its use may rarely cause fulminant hepatic failure. Methimazole is, therefore, the preferred antithyroid drug outside the first trimester of pregnancy; when antithyroid drugs are needed in the first trimester propylthiouracil is recommended.

Generally, doses of antithyroid drugs are lower in pregnancy, and maternal levels of free T4 are kept high-normal to slightly elevated.[34] Low-to-moderate doses (e.g., methimazole <20 mg/day) of antithyroid drugs can be used during lactation.[34]

Primary options

methimazole: 5-60 mg/day orally given once daily or in 2-3 divided doses; doses rarely exceed 40 mg/day in practice; consult specialist for guidance on dose in pregnancy

Secondary options

propylthiouracil: 50-400 mg/day orally given in 3 divided doses; consult specialist for guidance on dose in pregnancy

Consider – beta-blockers pending effects of definitive therapy

Back
ONGOING
|
mass effect or suspicion of cancer
|
with moderate or severe symptoms and/or increased cardiovascular risk
Consider – 

beta-blockers pending effects of definitive therapy

Treatment recommended for SOME patients in selected patient group

Used for symptoms such as palpitations, anxiety, or tremor, or in patients with increased cardiovascular risk.[3][42] Generally recommended for older adults with symptoms or younger people with heart rate >90 bpm.[13] Should be used with caution in older people and those with heart disease.

Dose should be gradually increased until symptoms and pulse are controlled, then gradually tapered when the patient is euthyroid.[3][44]

Useful before surgery and also before I-131 therapy, or while waiting for antithyroid drugs to take effect.[3]

A selective beta-blocker can be used in patients who cannot tolerate propranolol.

If beta-blockers are contraindicated, an alternative is a calcium-channel blocker such as diltiazem.

Consult specialist for guidance on choice of beta-blocker and dose in pregnancy.

Primary options

propranolol hydrochloride: 10-40 mg orally (immediate-release) four times daily, increasing if necessary until symptoms and pulse rate are controlled, usual dose is 80-160 mg/day although higher doses have been reported by some specialists

Secondary options

atenolol: 25-50 mg orally once daily, increase if necessary to 100 mg/day

pregnant or lactating: without mass effect or suspicion of cancer

1st line – antithyroid drugs

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ONGOING
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pregnant or lactating: without mass effect or suspicion of cancer
1st line – 

antithyroid drugs

Pregnant women should be managed by a multidisciplinary team. Maternal and fetal hypothyroidism must be avoided to prevent damage to fetal neural development, increased risk of miscarriage, or preterm delivery.[34]

Generally, doses of antithyroid drugs are lower in pregnancy, and maternal levels of free T4 are kept high-normal to slightly elevated.[34] Low-to-moderate doses (e.g., methimazole <20 mg/day) of antithyroid drugs can be used during lactation.[34]

Serious complications include agranulocytosis (0.1% to 0.3% of patients), liver toxicity, or vasculitis.[3][38]

Birth defects have been associated with both methimazole and propylthiouracil when used during the first trimester of pregnancy, although the defects associated with methimazole tend to be more severe.

Propylthiouracil does, however, have more frequent dosing compared with methimazole, and its use may rarely cause fulminant hepatic failure. Methimazole is, therefore, the preferred antithyroid drug outside the first trimester of pregnancy; when antithyroid drugs are needed in the first trimester propylthiouracil is recommended.

Primary options

propylthiouracil: 50-300 mg/day orally given in 3 divided doses; consult specialist for further guidance

OR

methimazole: 5-30 mg/day orally given once daily or in 2-3 divided doses; consult specialist for further guidance

2nd line – thyroid surgery

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ONGOING
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pregnant or lactating: without mass effect or suspicion of cancer
2nd line – 

thyroid surgery

Second-line option in pregnant women.[34] In pregnancy, surgery is indicated for uncontrolled hyperthyroidism due to adverse reaction or nonadherence to antithyroid drugs and is preferably performed in the second trimester.

An experienced, high-volume surgeon is recommended. Risk of complications, including recurrent laryngeal nerve damage and hypoparathyroidism, should be <2% if the surgeon is experienced.[43] Hypocalcemia due to hypoparathyroidism may be transient or permanent.

Reduction of thyroid function is immediate, although recurrent hyperthyroidism is possible and subsequent hypothyroidism is likely.

Consider – beta-blockers pending effects of definitive therapy

Back
ONGOING
|
pregnant or lactating: without mass effect or suspicion of cancer
|
with moderate or severe symptoms and/or increased cardiovascular risk
Consider – 

beta-blockers pending effects of definitive therapy

Treatment recommended for SOME patients in selected patient group

Used for symptoms such as palpitations, anxiety, or tremor in consultation with a specialist.[3][42]

Dose should be gradually increased until symptoms and pulse are controlled, then gradually tapered when the patient is euthyroid.[3][44]

Useful before surgery or while waiting for antithyroid drugs to take effect.[3]

Should be used with caution in those with heart disease.

Labetolol is considered the safest beta-blocker in pregnancy. Propranolol may be used for the short-term control of hyperthyroid symptoms in pregnant women, but its use has been associated with fetal bradycardia and growth restriction.

Primary options

labetalol: consult specialist for guidance on dose

OR

propranolol hydrochloride: consult specialist for guidance on dose

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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