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

ACUTE

thyroid storm

1st line – high-dose antithyroid drugs, corticosteroids, beta-blockers, iodine solution with supportive care

Back
ACUTE
|
thyroid storm
1st line – 

high-dose antithyroid drugs, corticosteroids, beta-blockers, iodine solution with supportive care

Thyroid storm is rare but typically develops in untreated or partially treated patients with poor access to the healthcare system.[86] It can occur at any time, depending on precipitating factors. Rarely, thyroid storm may be the initial presentation.

Thyroid storm most commonly occurs postoperatively in a patient who is not medically prepared for surgery (i.e., the patient has not achieved perioperative euthyroidism), or subsequent to the release of thyroid hormone following radioactive iodine therapy.[87][88]​ Prevention with antithyroid drugs is important.

Thyroid storm presents with volume depletion, congestive heart failure, confusion, nausea and vomiting, and extreme agitation. Management includes supportive treatment such as cooling, correction of volume status, respiratory support if indicated, and treatment of underlying sepsis if appropriate. Thyroid storm should be managed in an intensive care environment with input from endocrine specialists.

High doses of antithyroid medications, corticosteroids, beta-blockers, and iodine solution (e.g., Lugol solution, or saturated solution of potassium iodide [SSKI]) should also be administered.[89][90] Lugol solution must be given no earlier than 30 minutes after the first dose of antithyroid medication in order to avoid exacerbation of thyrotoxicosis due to escape from Wolff-Chaikoff effect. An alternative to Lugol solution and SSKI is sodium iodide, which is given intravenously; however, this is not available in some countries.[91]

Primary options

propylthiouracil: adults: 500-1000 mg orally initially as a loading dose, followed by 250 mg orally every 4 hours; 400-600 mg rectally every 6 hours

or

methimazole: adults: 60-120 mg/day orally given in divided doses every 4-6 hours

-- AND --

hydrocortisone: adults: 300 mg intravenously initially as a loading dose, followed by 100 mg every 8 hours

-- AND --

propranolol hydrochloride: adults: 60-80 mg orally (immediate-release) every 4-6 hours

or

esmolol: adults: 50-100 micrograms/kg/minute intravenous infusion

-- AND --

iodine/potassium iodide: (Lugol solution: iodine 5%/potassium iodine 10%) adults: 5 drops (250 mg) orally every 6 hours; consult specialist for guidance on rectal dose

or

potassium iodide: adults: (SSKI 1 g/mL) 0.1 to 0.3 mL (3-5 drops) orally three times daily

Consider – cholestyramine

Back
ACUTE
|
thyroid storm
Consider – 

cholestyramine

Treatment recommended for SOME patients in selected patient group

Cholestyramine, a bile acid-sequestering agent, may be given to patients with thyroid storm to reduce the enterohepatic circulation of thyroid hormones.

Primary options

cholestyramine: adults: 1-4 g orally twice daily

Consider – lithium

Back
ACUTE
|
thyroid storm
Consider – 

lithium

Treatment recommended for SOME patients in selected patient group

Lithium may be given to patients with thyroid storm to reduce thyroid hormone secretion.

Primary options

lithium: adults: 300 mg orally (regular-release) every 8 hours

ONGOING

subclinical Graves disease

1st line – individualized treatment

Back
ONGOING
|
subclinical Graves disease
1st line – 

individualized treatment

Treatment of subclinical disease is individualized. Subclinical hyperthyroidism is associated with increased risk of atrial fibrillation, and an increased risk of bone loss in postmenopausal women who are not receiving estrogen.[92] When thyroid-stimulating hormone (TSH) is persistently <0.1 mIU/L, US guidelines recommend treating subclinical hyperthyroidism in the following patient populations: all individuals ages ≥65 years; those with cardiac risk factors, heart disease, or osteoporosis; postmenopausal women who are not on estrogens or bisphosphonates; individuals with hyperthyroid symptoms.[50] 

Subclinical hyperthyroidism due to Graves disease has an unpredictable course. In one study (median follow-up 32 months), approximately one third of patients remaind in a subclinical hyperthyroid state, one third progressed to overt hyperthyroidism, and one third had spontaneous remission (normalized thyroid function); older individuals and those with positive antithyroid peroxidase (TPO) antibodies were at higher risk of progression.[16]

symptomatic nonpregnant, nonlactating adults

1st line – prolonged antithyroid drug therapy

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
1st line – 

prolonged antithyroid drug therapy

Antithyroid drugs, radioactive iodine, and surgery are all effective and relatively safe options for treating Graves hyperthyroidism.[81] Antithyroid drugs are increasingly the predominant therapy in developed countries.[94][95]​​[96]

Discuss the possible benefits and risks of these treatment options and the likelihood of a good response with patients (and their parents and caregivers, as appropriate) and take their preferences and values into account in addition to their clinical characteristics.

Antithyroid drugs block thyroid hormone synthesis. The group includes methimazole and propylthiouracil. Propylthiouracil also inhibits peripheral conversion of T4 to T3. This may be of benefit in the first few weeks of therapy in severe hyperthyroidism ("storm"), but methimazole is a more potent drug and results in a more rapid return of T3 into the normal range weeks earlier than propylthiouracil.

Antithyroid drugs are used for a prolonged period of time (typically 12-18 months,​​ but occasionally longer) to control the hyperthyroidism with the hope that the underlying autoimmune process will go into remission. [ Cochrane Clinical Answers logo ]

Unless hyperthyroidism is mild, antithyroid drugs are usually administered initially at higher doses and titrated to lower maintenance doses depending on the biochemical response. Alternatively, high-dose antithyroid drugs can be administered continuously and then levothyroxine given for replacement therapy when the patient becomes euthyroid, which is usually 4-8 weeks after commencing treatment (i.e., the "block and replace" approach).[102] The "block and replace" strategy has always been far more popular in Europe than in the US. The American Thyroid Association states that this approach is not generally recommended because it results in a higher rate of antithyroid drug adverse effects.[50] ​

European regulatory agencies have issued drug safety alerts regarding the risk of acute pancreatitis and the increased risk of congenital malformations (when administered during pregnancy) with the use of methimazole.[107][108][109]​ Propylthiouracil is associated with hepatic toxicity. Methimazole should be used initially in all patients except during the first trimester of pregnancy due to its increased association with birth defects.[48][110]

Adverse effects of antithyroid drugs include the following.

Skin rash: in 7% to 12% of patients; if mild, may improve with antihistamine treatment.[103][111]

Agranulocytosis: a rare adverse effect seen in 0.1% to 0.5% of patients.[112]​ All patients taking antithyroid drugs should be educated and warned about the early symptoms of agranulocytosis, and advised to stop taking the medication and seek urgent medical attention if these symptoms develop.[113]

Antineutrophil cytoplasmic antibody (ANCA)-positive small vessel vasculitis: symptoms manifest in approximately 3% of patients treated with antithyroid drugs; the risk is higher with propylthiouracil, younger patients, and increasing duration of treatment.[114]

Relapse rate after a full course of therapy is reported to vary between 50% and 70% of patients but it may be lower in iodine-deficient areas.[103][104]​​ If antithyroid drugs are discontinued because of adverse effects or if relapse occurs after a course of therapy, treatment with radioactive iodine therapy or, in selected cases, surgical thyroidectomy may be considered.[110]​​ Some patients prefer a second course or longer-term treatment with antithyroid drugs; there is some evidence that prolonged treatment may improve remission rates.[45][105][106]​​

Primary options

methimazole: adults: 10-30 mg/day orally given in 1-3 divided doses initially, adjust according to response; usual maintenance dose: 5-15 mg/day

OR

Block and replace regimen

methimazole: adults: 30 mg/day orally, titrate according to response

and

levothyroxine: adults: 100-150 micrograms/day orally when patient is euthyroid

Secondary options

propylthiouracil: adults: 150-400 mg/day orally given in 3 divided doses initially, adjust according to response; usual maintenance dose: 50-150 mg/day

OR

Block and replace regimen

propylthiouracil: adults: 400 mg/day orally given in 3 divided doses initially, titrate according to response

and

levothyroxine: adults: 100-150 micrograms/day orally when patient is euthyroid

Consider – symptomatic therapy

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
Consider – 

symptomatic therapy

Treatment recommended for SOME patients in selected patient group

Offer a beta-blocker such as propranolol for early symptomatic relief until specific therapy normalizes peripheral thyroid hormone levels. Beta-blockers ameliorate adrenergic symptoms such as tachycardia, tremor, and anxiety. Taper dose when specific therapy becomes effective. Beta-blockers are not indicated if there is history of asthma, bradycardia, or heart block.[2]​ Offer a calcium-channel blocker if beta-blockers are not tolerated or are contraindicated.

Primary options

propranolol hydrochloride: adults: 80-160 mg orally (extended-release) once daily

OR

atenolol: adults: 50-100 mg orally once daily

Secondary options

diltiazem: adults: 120-240 mg orally (extended-release) once daily

OR

verapamil: adults: 120-240 mg orally (extended-release) once daily

Consider – radioactive iodine for treatment failure

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
Consider – 

radioactive iodine for treatment failure

Treatment recommended for SOME patients in selected patient group

Radioactive iodine can be used as salvage therapy after failure of antithyroid drugs or surgery.[2]​​

1st line – radioactive iodine ± corticosteroid

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
1st line – 

radioactive iodine ± corticosteroid

Antithyroid drugs, radioactive iodine, and surgery are all effective and relatively safe options for treating Graves hyperthyroidism.[81]

Discuss the possible benefits and risks of these treatment options and the likelihood of a good response with patients (and their parents and caregivers, as appropriate) and take their preferences and values into account in addition to their clinical characteristics.

Radioactive iodine is used both as first-line treatment and salvage therapy after failure of antithyroid drugs or surgery.[2]​​

Treatment with radioactive iodine is associated with a reduced rate of recurrence of hyperthyroidism compared with treatment with antithyroid drugs.[98][115]​ The intention of radioactive iodine therapy is to ablate the thyroid. The major sequela is permanent hypothyroidism requiring lifelong thyroxine replacement therapy.[2]​​[93][116]

Transient hypothyroidism and recurrence of hyperthyroidism can occur in the initial months after therapy.[117][118][119]​​ Most patients will become hypothyroid following 6 months of radioactive iodine therapy if not replaced with levothyroxine. The aim should be to initiate levothyroxine before patients become clinically hypothyroid. Close monitoring is required.[50][119]​​​ Hypothyroidism after radioactive iodine should be avoided as it constitutes a risk factor for the development or progression of orbitopathy.[120][121]

​Attempts to partially ablate the thyroid and make the patient euthyroid are not successful and result in either late-onset hypothyroidism or relapse of hyperthyroidism. US guidelines recommend a single application of radioactive iodine sufficient to render patients with Graves disease hypothyroid (10–15 millicuries [mCi] [370-555 megabecquerels {MBq}]). The fixed dose should be given after confirmation of adequate thyroid uptake.[50]

Radioactive iodine is contraindicated in pregnancy and during lactation.[50]​ All women of childbearing age should have a pregnancy test prior to therapy.

Radioactive iodine is considered to be a poor choice for patients with active orbitopathy.[50] Studies have found development or aggravation of orbitopathy in 15% to 38% of patients after radioactive iodine therapy.[115][122][123]​​​ This may be prevented by concomitant corticosteroid therapy, especially for patients with preexisting mild or moderate orbitopathy.[60][123][124]​​ Corticosteroids alongside radioactive iodine therapy can be given in patients with active orbitopathy in the absence of contraindications and when other treatment options for hyperthyroidism are inappropriate or have failed.[60][125]​ A short course of prednisone tapered over 2-3 months is reasonable. Risks and benefits should be discussed with the patient.

An alternative approach is to wait until the orbitopathy is inactive before radioiodine treatment (without corticosteroids).

For patients with inactive or no evidence of orbitopathy, observation (without corticosteroids) is reasonable after radioactive iodine therapy without corticosteroids.

Radioactive iodine may present logistical barriers to its use due to the need for radiation precautions (e.g. for parents with young children, or older patients with incontinence [who may present unacceptable risk to their caregiver]).[127]

Primary options

prednisone: adults: 30-40 mg orally once daily for 4 weeks, then taper gradually over 2-3 months; lower doses may be as effective

Consider – antithyroid drug pre- and/or post-radioactive iodine

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
Consider – 

antithyroid drug pre- and/or post-radioactive iodine

Treatment recommended for SOME patients in selected patient group

Antithyroid drugs can be used as adjunctive therapy to normalize thyroid function before radioactive iodine therapy.

Pretreatment with an antithyroid drug may be considered for patients at increased risk of complications (e.g., older adults, very symptomatic patients, and those with comorbidities).[50]

Taken until the patient is euthyroid (usually several weeks), antithyroid drugs should be stopped before radioactive iodine therapy (generally 3 days before) and then restarted 3-5 days after completion of radioactive iodine therapy. Antithyroid drugs are then tapered and stopped as the patient becomes euthyroid or hypothyroid after radioactive iodine therapy (usually 1-3 months).[50]

European regulatory agencies have issued drug safety alerts regarding the risk of acute pancreatitis and the increased risk of congenital malformations (when administered during pregnancy) with the use of methimazole.[107][108][109]​ Propylthiouracil is associated with hepatic toxicity. Methimazole should be used initially in all patients except during the first trimester of pregnancy due to its increased association with birth defects.[48][110]

Adverse effects of antithyroid drugs include the following.

Skin rash: develops in 7% to 12% of patients; if mild, may improve with antihistamine treatment.[103][111]

Agranulocytosis: a rare adverse effect seen in 0.1% to 0.5% of patients.[112]​ All patients taking antithyroid drugs should be educated and warned about the early symptoms of agranulocytosis, and advised to stop taking the medication and seek urgent medical attention if these symptoms develop.[113]

Antineutrophil cytoplasmic antibody (ANCA)-positive small vessel vasculitis: symptoms manifest in approximately 3% of patients treated with antithyroid drugs; the risk is higher with propylthiouracil, younger patients, and increasing duration of treatment.[114]

Unless hyperthyroidism is mild, antithyroid drugs are usually administered initially at higher doses and titrated to lower maintenance doses depending on the biochemical response. Alternatively, high-dose antithyroid drugs can be administered continuously and then levothyroxine given for replacement therapy when the patient becomes euthyroid, which is usually 4-8 weeks after commencing treatment (i.e., the 'block and replace' approach).[102]​ The "block and replace" strategy has always been far more popular in Europe than in the US. The American Thyroid Association states that this approach is not generally recommended because it results in a higher rate of antithyroid drug adverse effects.[50]

Primary options

methimazole: adults: 10-30 mg/day orally given in 1-3 divided doses initially, adjust according to response; usual maintenance dose: 5-15 mg/day

OR

Block and replace regimen

methimazole: adults: 30 mg/day orally, titrate according to response

and

levothyroxine: adults: 100-150 micrograms/day orally when patient is euthyroid

Secondary options

propylthiouracil: adults: 150-400 mg/day orally given in 3 divided doses initially, adjust according to response; usual maintenance dose: 50-150 mg/day

OR

Block and replace regimen

propylthiouracil: adults: 400 mg/day orally given in 3 divided doses initially, titrate according to response

and

levothyroxine: adults: 100-150 micrograms/day orally when patient is euthyroid

Consider – symptomatic therapy

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
Consider – 

symptomatic therapy

Treatment recommended for SOME patients in selected patient group

Offer a beta-blocker such as propranolol for early symptomatic relief until specific therapy normalizes peripheral thyroid hormone levels.

Beta-blockers ameliorate adrenergic symptoms such as tachycardia, tremor, and anxiety.[2]​​ Taper dose when specific therapy becomes effective. Beta-blockers are not indicated if there is a history of asthma, bradycardia, or heart block.[2]​​ Calcium-channel blockers are an alternative if beta-blockers are not tolerated or are contraindicated.

Primary options

propranolol hydrochloride: adults: 80-160 mg orally (extended-release) once daily

OR

atenolol: adults: 50-100 mg orally once daily

Secondary options

diltiazem: adults: 120-240 mg orally (extended-release) once daily

OR

verapamil: adults: 120-240 mg orally (extended-release) once daily

Consider – post-therapy thyroid hormone replacement

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
Consider – 

post-therapy thyroid hormone replacement

Treatment recommended for SOME patients in selected patient group

Most patients will become hypothyroid by 6 months after radioactive iodine therapy if not replaced with levothyroxine. The aim should be to initiate levothyroxine before patients become clinically hypothyroid. Close monitoring is required.[50][119]​​​ Hypothyroidism after radioactive iodine should be avoided as it constitutes a risk factor for the development or progression of orbitopathy.[121]

Replacement thyroxine therapy should initially be monitored with serum thyroid-stimulating hormone (TSH) and free T4 at 6-week intervals until stable, then with serum TSH at least annually. Measurement of free T4 is a much less sensitive parameter of the thyroid metabolic state. However, when pituitary TSH production is suppressed by a prolonged period of thyrotoxic state due to high TSH receptor antibodies, it may take some months for pituitary function to recover; during that interval, measurement of serum TSH may be misleading, and free T4 may give a better indication of thyroid status.

Primary options

levothyroxine: adults: 1.7 micrograms/kg/day orally, adjust dose according to response and laboratory values

1st line – thyroid surgery

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
1st line – 

thyroid surgery

Antithyroid drugs, radioactive iodine, and surgery are all effective and relatively safe options for treating Graves hyperthyroidism.[81]​

Discuss the possible benefits and risks of these treatment options and the likelihood of a good response with patients (and their parents and caregivers, as appropriate) and take their preferences and values into account in addition to their clinical characteristics.

Surgery may be preferred in the following scenarios:[50]​

women planning a pregnancy in <6 months provided thyroid hormone levels are normal;

symptomatic compression or large goiters

relatively low uptake of radioactive iodine

cases when thyroid malignancy is documented or suspected

large thyroid nodules

coexisting hyperparathyroidism requiring surgery

and patients with moderate-to-severe active Graves orbitopathy.

Surgery may be open or employ a minimally invasive approach. Total or near-total thyroidectomy is preferred over bilateral subtotal thyroidectomy as it prevents recurrent hyperthyroidism; if the patient is euthyroid at the time of surgery, levothyroxine is started immediately postoperatively.[129][130] [ Cochrane Clinical Answers logo ] [Evidence B]

The incidence of hypoparathyroidism and vocal cord paralysis (recurrent laryngeal nerve damage) following surgery by experienced surgeons is approximately 2% and 1%, respectively.[131] Whether intraoperative monitoring of the recurrent laryngeal nerve reduces complications is controversial.[132][133]

Other surgical risks include bleeding, infection, and keloid formation. Endoscopic minimally invasive surgery appears to be associated with reduced rates of blood loss and better cosmetic results compared with open surgery, but with longer operation times.[131]​ Rates of transient recurrent laryngeal nerve palsy, transient hypocalcemia, postoperative hypothyroidism, and recurrent hyperthyroidism were equivalent between the minimally invasive and open groups.[134] Several factors inform suitability for minimally invasive surgery, including total thyroid volume not exceeding 25 mL as measured by ultrasound.[135] Total or near-total thyroidectomy is preferred over bilateral subtotal thyroidectomy as it prevents recurrent hyperthyroidism; if the patient is euthyroid at the time of surgery, levothyroxine therapy is started immediately postoperatively.[130][148][149] [ Cochrane Clinical Answers logo ] [Evidence B]

Plus – preoperative medical preparation

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
Plus – 

preoperative medical preparation

Treatment recommended for ALL patients in selected patient group

Antithyroid drugs can be used as adjunctive therapy to normalize thyroid function before surgery. Antithyroid drugs are stopped at the time of thyroidectomy.[50]

Some clinics treat patients 7-10 days prior to surgery with pharmacologic doses of iodine (e.g., Lugol solution or SSKI) to reduce vascularity of the thyroid gland, leading to less intraoperative blood loss.[128]​ Iodine is contraindicated in pregnancy at all times as it may inhibit fetal thyroid function to an extent that goiter and even congenital hypothyroidism may ensue.

European regulatory agencies have issued drug safety alerts regarding the risk of acute pancreatitis and the increased risk of congenital malformations (when administered during pregnancy) with the use of methimazole.[107][108][109]​ Propylthiouracil is associated with hepatic toxicity. Methimazole should be used initially in all patients except during the first trimester of pregnancy due to its increased association with birth defects.[48][110]

Adverse effects of antithyroid drugs include the following.

Skin rash: develops in 7% to 12% of patients; if mild, may improve with antihistamine treatment.[103][111]

Agranulocytosis: a rare adverse effect seen in 0.1% to 0.5% of patients.[112]​ All patients taking antithyroid drugs should be educated and warned about the early symptoms of agranulocytosis, and advised to stop taking the medication and seek urgent medical attention if these symptoms develop.[113]

Antineutrophil cytoplasmic antibody (ANCA)-positive small vessel vasculitis: symptoms manifest in approximately 3% of patients treated with antithyroid drugs; the risk is higher with propylthiouracil, younger patients, and increasing duration of treatment.[114]

Offer a beta-blocker such as propranolol for early symptomatic relief until surgery normalizes peripheral thyroid hormone levels. Beta-blockers ameliorate adrenergic symptoms such as tachycardia, tremor, and anxiety.[2]​​ Taper dose following surgery. Beta-blockers are not indicated if there is a history of asthma, bradycardia, or heart block.[2]​​ Calcium-channel blockers are an alternative if beta-blockers are not tolerated or are contraindicated.

Primary options

propranolol hydrochloride: adults: 80-160 mg orally (extended-release) once daily

or

atenolol: adults: 50-100 mg orally once daily

-- AND / OR --

methimazole: adults: 10-30 mg/day orally given in 1-3 divided doses initially, adjust according to response; usual maintenance dose: 5-15 mg/day

or

propylthiouracil: adults: 150-400 mg/day orally given in 3 divided doses initially, adjust according to response; usual maintenance dose: 50-150 mg/day

-- AND / OR --

iodine/potassium iodide: (Lugol solution: iodine 5%/potassium iodine 10%) adults: 5 drops (250 mg) orally every 6 hours for 7-10 days before surgery

or

potassium iodide: adults: (SSKI 1 g/mL) 0.1 to 0.3 mL (3-5 drops) orally three times daily for 7-10 days before surgery

Plus – postoperative thyroid replacement

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
Plus – 

postoperative thyroid replacement

Treatment recommended for ALL patients in selected patient group

Treatment with levothyroxine is as indicated for hypothyroidism. Replacement thyroxine therapy should initially be monitored with serum thyroid-stimulating hormone (TSH) and free T4 at 6-week intervals until stable, then with serum TSH at least annually. Measurement of free T4 is a much less sensitive parameter of the thyroid metabolic state. However, when pituitary TSH production is suppressed by a prolonged period of thyrotoxic state due to high TSH receptor antibodies, it may take some months for pituitary function to recover; during that interval, measurement of serum TSH may be misleading, and free T4 may give a better indication of thyroid status.

Primary options

levothyroxine: adults: 1.7 micrograms/kg/day orally, adjust dose according to response and laboratory values

Consider – radioactive iodine for treatment failure

Back
ONGOING
|
symptomatic nonpregnant, nonlactating adults
Consider – 

radioactive iodine for treatment failure

Treatment recommended for SOME patients in selected patient group

Radioactive iodine can be used as salvage therapy after failure of antithyroid drugs or surgery.[2]​​

pregnant women

1st line – antithyroid drug

Back
ONGOING
|
pregnant women
1st line – 

antithyroid drug

Antithyroid drugs are used to treat pregnant women; radioactive iodine is contraindicated in pregnancy.

Antithyroid drugs can cross the placenta and affect fetal thyroid function, so the lowest possible dose should be used.[107]​ The goal of treatment is a serum free T4 level at, or moderately above, the normal range for pregnancy.[78]​ Therefore, many women with mild hyperthyroidism during pregnancy are closely monitored and not treated. However, data from a population-based prospective cohort study indicated a negative impact of mild maternal thyrotoxicosis on the IQ of the offspring.[136]

Women who are already on treatment with antithyroid drugs for managing Graves disease and who are contemplating pregnancy should be switched to propylthiouracil (if on methimazole therapy). When pregnancy is confirmed and if the disease appears to be in remission (low or negative thyroid-stimulating hormone [TSH] receptor antibodies) antithyroid drugs can be withdrawn and thyroid functions repeated.[78]

Propylthiouracil is preferred in the first trimester of pregnancy. While all antithyroid drugs have been associated with birth defects, those associated with methimazole are more common and more severe than those associated with propylthiouracil.[137][138][139]

One systematic review and meta-analysis of observational studies reported the following absolute excess risks associated with antithyroid drug exposure (compared with an unexposed general population) for birth defects (any/major): propylthiouracil (10.2/1.3 per 1000 live births); methimazole (17.8/2.3); untreated hyperthyroidism (9.6/1.2).[139]

US guidelines on the management of thyroid disease in pregnancy state that consideration can be given to discontinuing propylthiouracil after the first trimester and switching to methimazole in order to decrease the risk of liver failure in the mother. However, due to insufficient evidence, it makes no recommendation.[78]​ Treatment can continue for 12-18 months. Relapse rate after a full course of therapy is reported to vary between 50% and 70% of patients.[103]​ It is possible to discontinue treatment with antithyroid drugs in 20% to 30% of women in the last trimester of pregnancy.[78]

Antithyroid drugs at low to moderate doses are thought to be safe for infants of lactating women.[78]

European regulatory agencies have issued drug safety alerts regarding the risk of acute pancreatitis and the increased risk of congenital malformations (when administered during pregnancy) with the use of methimazole.[107][108][109]​ Propylthiouracil is associated with hepatic toxicity. Methimazole should be used initially in all patients except during the first trimester of pregnancy due to its increased association with birth defects.[48][110]

Adverse effects of antithyroid drugs include the following.

Skin rash: develops in 7% to 12% of patients; if mild, may improve with antihistamine treatment.[103][111]

Agranulocytosis: a rare adverse effect seen in 0.1% to 0.5% of patients.[112]​ All patients taking antithyroid drugs should be educated and warned about the early symptoms of agranulocytosis, and advised to stop taking the medication and seek urgent medical attention if these symptoms develop.

If antithyroid drugs are discontinued because of adverse effects during pregnancy, second-trimester thyroidectomy is the only other option for symptomatic patients.[110]

Primary options

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

OR

methimazole: adults: 5-30 mg/day orally given in 1-3 divided doses initially, consult specialist for further guidance

Consider – symptomatic therapy

Back
ONGOING
|
pregnant women
Consider – 

symptomatic therapy

Treatment recommended for SOME patients in selected patient group

Offer a beta-blocker such as propranolol for early symptomatic relief until specific therapy normalizes peripheral thyroid hormone levels.

Beta-blockers ameliorate adrenergic symptoms such as tachycardia, tremor, and anxiety. Taper dose when specific therapy becomes effective. Beta-blockers are not indicated if there is a history of asthma, bradycardia, or heart block.[2]​​

Propranolol has been associated with neonatal hypoglycemia, apnea, and bradycardia as well as intrauterine growth restriction, so its use should be minimized or fetal growth should be closely monitored if it is used long-term.[150]

Calcium-channel blockers are discouraged as their effects on the fetus are not known.

Primary options

propranolol hydrochloride: adults: 80-160 mg orally (extended-release) once daily

OR

labetalol: adults: 100-200 mg orally twice daily

2nd line – thyroid surgery

Back
ONGOING
|
pregnant women
2nd line – 

thyroid surgery

Surgery during pregnancy is rarely necessary, as low-dose antithyroid drug treatment usually suffices. If antithyroid drugs are discontinued because of adverse effects during pregnancy, second-trimester thyroidectomy is the only other option for symptomatic patients.[110]

Plus – preoperative medical preparation

Back
ONGOING
|
pregnant women
Plus – 

preoperative medical preparation

Treatment recommended for ALL patients in selected patient group

Beta-blockers are initiated in preparation for second-trimester thyroidectomy in patients with adverse effects to antithyroid drugs.

Beta blockers are stopped after surgery.

Primary options

propranolol hydrochloride: adults: 80-160 mg orally (extended-release) once daily

OR

labetalol: adults: 100-200 mg orally twice daily

Plus – postoperative thyroid replacement

Back
ONGOING
|
pregnant women
Plus – 

postoperative thyroid replacement

Treatment recommended for ALL patients in selected patient group

Hypothyroidism must be avoided during pregnancy to avert adverse effects on the fetus.

Treatment with levothyroxine is as indicated for hypothyroidism. Replacement thyroxine therapy should be monitored with serum thyroid-stimulating hormone (TSH) at 4-week intervals until stable during pregnancy. Measurement of FT4 is a much less sensitive parameter of the thyroid metabolic state. However, when pituitary TSH production is suppressed by a prolonged period of thyrotoxic state due to high TSH receptor antibodies, it may take some months for pituitary function to recover; during that interval, measurement of serum TSH may be misleading, and free T4 may give a better indication of thyroid status. Dose requirements may reduce after delivery, and will again need to be titrated. Once stable, TSH should be measured at least annually.

Primary options

levothyroxine: adults: consult specialist for guidance on dose

children

1st line – antithyroid drugs (prolonged)

Back
ONGOING
|
children
1st line – 

antithyroid drugs (prolonged)

Antithyroid drugs, radioactive iodine, and surgery are options for treating Graves hyperthyroidism in children.[48][140]​

Discuss the possible benefits and risks of these treatment options and the likelihood of a good response with patients (and their parents and caregivers, as appropriate) and take their preferences and values into account in addition to their clinical characteristics.

In children, antithyroid drug treatment is considered first choice, but results in a relapse rate of about 70% after 1-2 years.[50][141][142]​​​ However, prolonged treatment (8-10 years) may be associated with up to a 50% remission rate.[143] In these cases, low-dose drug treatment until maturity is appropriate, then surgery (only by experienced pediatric surgeons) or radioiodine should be considered.[144]

Propylthiouracil has an unacceptable risk of life-threatening hepatic injury in children, and should only be used rarely for brief periods (e.g., while waiting for thyroidectomy).[110]

Primary options

methimazole: children: consult specialist for guidance on dose

Secondary options

propylthiouracil: children: consult specialist for guidance on dose

Consider – symptomatic therapy

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children
Consider – 

symptomatic therapy

Treatment recommended for SOME patients in selected patient group

Offer a beta-blocker such as propranolol for early symptomatic relief until specific therapy normalizes peripheral thyroid hormone levels.

Beta-blockers ameliorate adrenergic symptoms such as tachycardia, tremor, and anxiety. Taper dose when specific therapy becomes effective. Beta-blockers are not indicated if there is a history of asthma, bradycardia, or heart block.[2]​​

Calcium-channel blockers are an alternative if beta-blockers are not tolerated or are contraindicated.

Primary options

propranolol hydrochloride: children: consult specialist for guidance on dose

Secondary options

atenolol: children: consult specialist for guidance on dose

Tertiary options

diltiazem: children: consult specialist for guidance on dose

OR

verapamil: children: consult specialist for guidance on dose

2nd line – thyroid surgery

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children
2nd line – 

thyroid surgery

Surgery is preferred for younger children (e.g., <5 years) and those with Graves orbitopathy or a thyroid nodule.[50][140][145]

Surgery is, however, usually a second-line option for children, and can be considered: if a child experiences severe adverse effects with antithyroid therapy; when prolonged therapy has not resulted in remission; or when relapse occurs after a course of antithyroid treatment.

Surgical complications are more common in children than in adults.​​​[145][146]​ Minimally invasive thyroid surgery may be considered in some patients.[135][147]​ Total or near-total thyroidectomy is preferred over bilateral subtotal thyroidectomy as it prevents recurrent hyperthyroidism; levothyroxine therapy is started immediately postoperatively if the patient is euthyroid at the time of surgery.[130][148][149]

Radioactive iodine may be an alternative option for children aged over 10 years. It should only be considered for those ages 5-10 years if surgery is not an option. Radioactive iodine should be avoided in children under 5 years old.

Plus – preoperative medical preparation

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children
Plus – 

preoperative medical preparation

Treatment recommended for ALL patients in selected patient group

If surgery is considered appropriate, patients are prepared with antithyroid drugs until euthyroidism is achieved. Some clinics treat patients 7-10 days prior to surgery with pharmacologic doses of iodine (e.g., Lugol solution or SSKI) to reduce vascularity of the thyroid gland.

Beta-blockers are used for symptomatic therapy; calcium-channel blockers are an alternative if beta-blockers are not tolerated or are contraindicated.[2]​​[145]

Primary options

propranolol hydrochloride: children: consult specialist for guidance on dose

or

atenolol: children: consult specialist for guidance on dose

-- AND / OR --

methimazole: children: consult specialist for guidance on dose

or

propylthiouracil: children: consult specialist for guidance on dose

-- AND / OR --

iodine/potassium iodide: (Lugol solution: iodine 5%/potassium iodine 10%) children: consult specialist for guidance on dose

or

potassium iodide: children: consult specialist for guidance on dose

Plus – postoperative thyroid replacement

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children
Plus – 

postoperative thyroid replacement

Treatment recommended for ALL patients in selected patient group

Total or near-total thyroidectomy is preferred over bilateral subtotal thyroidectomy as it prevents recurrent hyperthyroidism; levothyroxine therapy is started immediately postoperatively if the patient is euthyroid at the time of surgery.[130][148][149]

Primary options

levothyroxine: children: 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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