Graves disease

Graves disease (GD) is an autoimmune condition in which TSH receptor autoantibodies stimulate the thyroid gland, resulting in increased thyroid hormone production. This condition is the most common cause of hyperthyroidism. Clinical features include symptoms of hyperthyroidism, diffuse goiter, Graves ophthalmopathy, and thyroid dermatopathy (i.e., pretibial myxedema), although presentation often differs with patient age. Diagnosis is confirmed by clinical presentation and thyrotoxocosis on thyroid function testing. In diagnostic uncertainty, elevated TSH receptor antibody (TRAb) levels or characteristic findings on thyroid imaging can confirm the diagnosis. Treatment includes symptomatic therapy for thyrotoxicosis with beta blockers, if needed, combined with therapeutic management with one of three options: antithyroid drugs for GD, radioactive iodine ablation (RAIA) or thyroid surgery. Treatment choice depends on many factors, including patient characteristics (e.g., age, pregnancy, preference) and clinical presentation (e.g., size of goiter, TRAb levels). Ongoing management for GD involves monitoring for disease recurrence and side effects of treatment.

• Most common cause of hyperthyroidism in the United States
• Incidence: ∼ 30 cases per 100,000 people per year
• Sex: ♀ > ♂ (∼10:1)
• Typical age range: 20–50 years

Epidemiological data refers to the US, unless otherwise specified.

• Genetic predisposition
  • 50% of individuals with Graves disease have a family history of autoimmune disorders (e.g., type 1 diabetes mellitus, Hashimoto disease, pernicious anemia, myasthenia gravis).
  • Associated with HLA-DR3 and HLA-B8 alleles
• Autoimmunity: B and T lymphocyte-mediated disorder
• Triggers
  • Infectious agents: Yersinia enterocolitica and Borrelia burgdorferi have been shown to trigger antigen mimicry for homologies between their protein constituents and thyroid autoantigens.
  • Stress
    • Physical: surgery, trauma
    • Psychological
  • Pregnancy (see “Hyperthyroidism in pregnancy”) ^[2]
  • Environmental factors: smoke, irradiations, drugs, endocrine disruptors

References:^[1][3]

• General mechanism: B and T cell-mediated autoimmunity → production of stimulating immunoglobulin G (IgG) against TSH-receptor (TRAb; type II hypersensitivity reaction) → ↑ thyroid function and growth → hyperthyroidism and diffuse goiter
• Thyroid-associated ophthalmopathy: activated B and T cells infiltrate retro-orbital space targeting orbital fibroblasts → cytokine release (e.g. TNF-α, IFN-γ) → local inflammatory response → fibroblast proliferation and differentiation to adipocytes → production of hyaluronic acid and GAGs and increased amount of adipocytes → increase in the volume of intraorbital fat and muscle tissues → exophthalmos, lid retraction, disturbances in ocular motility (causing diplopia)
• Pretibial myxedema: dermal fibroblast stimulation and deposition of glycosaminoglycans in connective tissue

References:^[4]

• Symptoms of hyperthyroidism
• Diffuse goiter ^[6]
  • Smooth, uniformly enlarged goiter
  • Bruit may be heard at the superior and/or inferolateral poles of the thyroid gland. ^[7]
  • Pemberton sign
• Ophthalmopathy (see Graves ophthalmopathy)
  • Exophthalmos
  • Ocular motility disturbances
  • Lid retraction and conjunctival conditions
• Thyroid dermopathy ; ^[6][8]
  • Usually manifests as bilateral pretibial nonpitting edema and skin thickening (pretibial myxedema)
  • Plaques and/or nodules may be seen.
  • May also occur on other areas of the skin (e.g., after skin trauma)
• Patchy vitiligo ^[6]
• Thyroid acropachy ^[5][6]
• Severe disease: thyroid storm

Pretibial myxedema and thyroid acropachy are rare manifestations of Graves disease that typically occur in patients with Graves ophthalmopathy. ^[5][8]

Graves ophthalmopathy ^[9]

Graves ophthalmopathy or orbitopathy (GO), also known as thyroid-associated orbitopathy/ophthalmopathy (TAO), is an autoimmune condition that is generally associated with Graves disease

Etiology

• TAO is not due to the thyroid disorder, rather due to an autoimmune antibody reaction.
• Associated with hyperthyroidism (most common); , euthyroidism, hypothyroidism such as Hashimoto's thyroiditis; , other autoimmune disorders, thyroid cancer, and neck irradiation.

Epidemiology

• Sex: ♀ > ♂
• Risk factors: family history of Graves disease and tobacco smoking
• Severe Graves ophthalmopathy is more common in older adults. ^[9]

Pathophysiology

• TSH autoantibodies are present in the orbital cavity (eye socket) → bind TSH receptor antigen (autoimmune reaction) on cells → lymphocytic infiltration into the orbital tissues → inflammation and release of cytokines from CD4+ T cells → stimulates fibroblasts to secrete glycosaminoglycans (hyaluronic acid), which also pulls water into the interstitial space (osmotic effect) ; → expansion of retro-orbital tissue due to increased fluid in extraocular muscles, lymphocytic infiltration, and adipogenesis

Clinical features

• Exophthalmos : can be unilateral or bilateral, often asymmetric. Retropulsion (palpation of the globe while the eyelid is closed) enables adequate examination.
• Ocular motility disturbances
  • Binocular diplopia
  • Poor convergence (Moebius sign)
  • Restriction of one or more extraocular muscles (Ballet sign)
• Lid retraction, also known as “thyroid stare”
  • Dalrymple sign: retraction of the upper eyelid with visible sclera and extended palpebral fissure
  • Von Graefe sign: lagging of the upper eyelid on downgaze (may occur with Grove sign: resistance to pulling the retracted upper lid down)
  • Stellwag sign: infrequent and incomplete blinking (rare)
  • Vigouroux sign: Eyelid fullness
  • Lagophthalmos → keratitis (occurs with insufficient blinking)
• Joffroy sign: absent forehead creases during superior gaze
• Conjunctival injection and chemosis
• Ocular discomfort (pain or pressure)
• Photopsia on upward gaze
• Patient may also have clinical features of hyperthyroidism or clinical features of hypothyroidism.

Diagnostics

• Laboratory analysis: ↓ TSH and ↑ free T3/T4 (to diagnose of hyperthyroidism), ↑ TSH receptor antibodies, which are specific and sensitive to Graves disease but not widely available
• Comprehensive eye examination including slit lamp examination
• CT: confirmatory test that shows exophthalmos, increased fat density, inflammation, and enlargement of extraocular muscles
• MRI: alternative option to CT that can show similar findings to CT and, additionally, compression of the optic nerve
• Photo documentation

Differential diagnosis

Pseudoproptosis: the appearance of protrusion or bulging of the eye(s) that is not due to anterior displacement of the eye

Treatment

• Usually a self-limiting disease, but intervention may be necessary because of severe symptoms or risk of complications.

• All patients
  • Refer to endocrinology and ophthalmology.
  • Conservative local measures
    • Eye protection (e.g., artificial tears, sunglasses)
    • Sleep with the head of the bed elevated
  • Treat hyperthyroidism, if present
    • Usually with thioamides and/or surgery
    • Radioactive iodine ablation (RAIA) can be used for patients with mild disease (contraindicated in moderate-to-severe disease)
  • Smoking cessation
• Mild disease: transient or no diplopia, mild soft tissue involvement, lid retraction < 2 mm, proptosis < 3 mm
  • Conservative measures are usually sufficient
  • Selenium may be considered, if deficient ^[10]
• Moderate to severe disease: inconstant or constant diplopia, moderate to severe soft tissue involvement, lid retraction ≥ 2 mm, proptosis ≥ 3 mm
  • High-dose IV steroids
  • Nonresponders or threatened/manifest vision loss (See “Orbital compartment syndrome.”)
    • Orbital decompression surgery (following steroid administration)
    • Strabismus correction
    • Lid-lengthening surgery
    • Blepharoplasty
    • For patients who are refractory to treatment or poorly tolerate glucocorticoids: teprotumumab, rituximab, cyclosporine, octreotide, intravenous immunoglobulin, and tarsorrhaphy ^[11]

Goals of therapy include treatment of hyperthyroidism, smoking cessation, eye protection, and decreasing inflammation.

Approach ^[6][9][12]

• Obtain thyroid function tests.
• Confirmed hyperthyroidism: Assess for clinical features of GD to determine if diagnostic criteria for GD have been met.
• If patients do not meet diagnostic criteria, order confirmatory studies for GD.
• Consider additional studies based on clinical findings, e.g.:
  • Thyroid nodules: Initiate workup for thyroid nodules.
  • Graves ophthalmopathy: comprehensive eye examination with consideration of imaging
• For additional studies indicated in pregnancy, see “GD in pregnancy.”

Stabilize individuals with life-threatening conditions (e.g., thyroid storm, arrhythmia, hemodynamic instability) before diagnostic testing. ^[9]

Diagnostic criteria for GD ^[9]

GD can be diagnosed without further testing in patients who meet all of the following criteria:

• Overt hyperthyroidism ^[6][9][12]
  • TSH: decreased or undetectable ^[9][12]
  • Free T₄ and total T₃: increased ^[9]
• New onset of features of Graves ophthalmopathy
• Symmetric enlargement of the thyroid gland (goiter)

Confirmatory studies for GD ^[9]

• Options include TSH receptor antibodies and thyroid imaging studies.
• Choice of test depends on availability, cost, and treatment preference. ^[9]

TSH receptor antibodies (TRAbs) ^[9][12][13]

• Elevated levels of stimulating TRAbs are specific to GD. ^[12]
• TRAbs can be negative in very mild GD. ^[9]

Antithyroid peroxidase antibodies (anti-TPO) and thyroglobulin antibodies (TgAbs) can be elevated in all forms of autoimmune thyroid disease and are not specific to Graves disease. ^[14]

Thyroid imaging in Graves disease ^[9][12][15]

• Nuclear medicine thyroid scan and radioactive iodine uptake measurement: often the imaging modality of choice ^[9]
  • Indications: nonpregnant adults with thyrotoxicosis of unknown cause
  • Findings: diffuse thyroid enlargement, diffuse uptake of radioactive iodine (¹²³I) ^[16]
• Thyroid ultrasound with color Doppler
  • Indications
    • Preferred thyroid imaging for pregnant or lactating individuals with thyrotoxicosis of unknown cause ^[9]
    • Any individual with an asymmetric or nodular thyroid gland (see “Workup of thyroid nodules”)
  • Findings: enlarged, hypervascular, hypoechoic thyroid gland ^[9][12][17]

Radioactive iodine uptake scans are contraindicated during pregnancy and lactation. See “GD in pregnancy.” ^[9]

• Macroscopic
  • Diffuse, uniform gland enlargement
  • Cut surfaces show beefy red appearance
• Microscopic: histological features of an overactive gland
  • Diffuse hyperplasia of thyroid follicles
  • Tall, hyperplastic and hypertrophic follicular cells
  • Colloid reabsorption with peripheral scalloping
  • Irregular stromal lymphocytic infiltration

References:^[18]

The following information pertains to nonpregnant adults. For information on managing GD in all other patient groups, see “Special patient groups.”

Approach ^[6][9]

• Initiate symptomatic therapy for thyrotoxicosis including, if necessary, treatment of thyroid storm. ^[9]
• Refer all patients to endocrinology for treatment of GD.
• Consider further referrals depending on clinical features.
  • Graves ophthalmopathy : ophthalmology ^[19]
  • Significant cardiac features, e.g., thyrotoxicosis-induced cardiac failure: cardiology
• Provide ongoing management for GD.

Graves ophthalmopathy can be sight-threatening. Immediately refer all patients with orbital pain, impaired vision or diplopia, impaired eye movement, or afferent pupillary defect to ophthalmology. ^[19]

Treatment of Graves disease ^[9]

• Options include:
  • Antithyroid drugs for GD
  • Definitive treatment:
    • Radioactive iodine ablation
    • Thyroid surgery
• Use shared decision-making to determine the most appropriate choice for the patient. ^[9][12]

Antithyroid drugs (ATDs) for Graves disease ^[6][9][12]

For more detailed information, including dosages and how to initiate therapy, see “Medications for hyperthyroidism.”

• Indications ^[9]
  • Individuals with a high likelihood of remission, e.g.: ^[9][12]
    • Mild disease
    • Small goiter ^[9]
    • Low TRAb titers
  • Pregnant individuals ^[9]
  • Poor surgical candidates ^[9]
  • Individuals with moderate to severe Graves ophthalmopathy ^[9]
  • As an adjunctive treatment to achieve euthyroidism before and/or after RAIA or thyroid surgery
• Options
  • Thionides (preferred): methimazole (MMI) or carbimazole (not available in the US) ^[9][12]
  • Pregnant patients: propylthiouracil ^[9][12]
  • Potassium iodide: if other options are not tolerated
• Additional considerations ^[9]
  • If unsuccessful, RAIA or thyroid surgery may be required. ^[9]
  • Effective treatment requires a high degree of adherence; definitive therapy may be preferred for individuals with risk factors for poor adherence.
• Complications of ATD therapy ^[9]
  • Agranulocytosis: Obtain a CBC in patients with fever and/or pharyngitis.
  • Hepatotoxicity: Obtain liver chemistries in patients with symptoms of liver failure.

Radioactive iodine ablation (RAIA) ^{[9] [6]}

For additional information see “RAIA” in “Definitive therapy for hyperthyroidism and thyrotoxicosis.”

• Indications ^[9]
  • Desire for definitive treatment and either wishes to avoid or is at increased risk from surgery
  • Planned pregnancy in > 6 months
  • Presence of any of the following conditions:
    • Thyrotoxic periodic paralysis
    • Pulmonary hypertension
    • Heart failure
    • Contraindications to ATDs
• Contraindications
  • Pregnant and/or lactating patients
  • Patients unable to follow radiation safety regulations
  • Patients with confirmed or suspected thyroid cancer
  • Other treatment modalities are preferred in patients:
    • With Graves ophthalmopathy ^[9][20]
    • Age < 5 years ^[9]
• Additional considerations
  • Patients often require additional medical management. ^[9]
    • Prior to the procedure: RAIA can transiently worsen symptoms, consider prophylactic use of ATDs for GD and symptomatic therapy for thyrotoxicosis for patients at increased risk.
    • After the procedure: Iatrogenic hypothyroidism can occur, requiring lifelong levothyroxine replacement.
  • Retreatment with RAIA can be considered after 3–6 months if hyperthyroidism persists. ^[9]

RAIA is contraindicated during pregnancy. Test for pregnancy no more than 48 hours prior to RAIA in all patients of reproductive age. ^[9]

Thyroid surgery ^[6][9]

For more detailed information, see “Thyroid surgery for hyperthyroidism.”

• Indications ^[9]
  • Desire for definitive treatment and RAIA is unlikely to be successful (i.e. low uptake on RAIU testing)
  • Anticipated pregnancy within 6 months
  • Presence of the following conditions:
    • Suspected thyroid cancer
    • Hyperparathyroidism or thyrotoxic periodic paralysis
    • Moderate to severe Graves ophthalmopathy
    • Large and/or symptomatic goiter
• Options: Near-total thyroidectomy or total thyroidectomy ^[9]
• Additional considerations
  • Results in iatrogenic hypothyroidism requiring lifelong thyroid hormone replacement
  • Complications of thyroid surgery can be serious; to reduce the risk:
    • An experienced thyroid surgeon is highly recommended. ^[9][21]
    • Optimize medical management as part of preparation for thyroid surgery. ^[9][20]
    • Follow postprocedural care for thyroid surgery.

Patients who have undergone thyroid surgery require lifelong thyroid hormone replacement and may additionally develop permanent hypoparathyroidism. ^[9]

Ongoing management for GD ^[9]

• Encourage smoking cessation in individuals with GD. ^[9]
• Ongoing management for patients treated for hyperthyroidism involves follow-up with endocrinology, surgery, and ophthalmology, as indicated.
• For patients on ATDs, endocrinology may stop medication after 12–18 months if TSH and TRAb levels are normal. ^[9]
• For patients who wish to conceive, discuss options (see “Graves disease in individuals planning pregnancy”).

Graves disease can manifest differently in certain patient groups, and treatment modifications may be required due to factors such as age or pregnancy status.

• Optimize management of GD before conception.
• Advise patients to avoid pregnancy until:
  • TFTs have been in the normal range for at least 1 month
  • At least 6 months have passed after receiving RAIA (if performed)
• For patients taking ATDs for GD, discuss management options, e.g.:
  • Definitive treatment for hyperthyroidism before conception
  • Switching from methimazole to propylthiouracil before conception or as soon as pregnancy is confirmed
  • An ATD discontinuation trial as soon as pregnancy is confirmed
• If pregnancy occurs, provide management of GD in pregnancy.

Hyperthyroidism occurs in < 1% of pregnancies, with ∼ 95% of cases caused by GD. hCG-mediated hyperthyroidism occurs in 1–3% of early pregnancies and is the main differential diagnosis for GD in pregnancy.

Clinical features

• Clinical features of GD are similar between pregnant and nonpregnant adults.
• Some symptoms of hyperthyroidism (e.g., heat intolerance, palpitations, mild thyroid enlargement) overlap with symptoms of pregnancy, which may delay recognition of hyperthyroidism. ^[1]

Diagnosis of GD in pregnancy ^[9][22][23]

For screening, see “Pregnant individuals at risk for thyroid disease” in “Prenatal care.”

• Diagnosis of hyperthyroidism in pregnancy relies on interpreting elevated thyroid hormones using trimester-specific reference ranges. ^[22]
  • TSH reference ranges are lower during pregnancy.
  • Total T₄ and total T₃ reference ranges are higher during pregnancy.
  • Free T₄ reference ranges vary by trimester.
• Diagnostics of GD are similar to nonpregnant individuals with the following modifications:
  • All patients with suspected or confirmed GD should have a TRAb measurement
  • The imaging study of choice is thyroid US ^[22][23]
  • In diagnostic uncertainty, serum hCG should be measured for differentiation of GD from hCG-mediated hyperthyroidism.
• Additional testing may be required to identify infants at risk for neonatal GD, see “Screening for neonatal GD”

Nuclear medicine thyroid scans and radioactive iodine uptake measurements are contraindicated during pregnancy. ^[22][23]

Management of GD in pregnancy

• Coordinate management with obstetrics, maternal-fetal medicine, and/or endocrinology specialists.
• Symptomatic patients: Consider a low-dose beta-blocker (propranolol or metoprolol) for 2–6 weeks. ^[9][22]
• For treatment of GD, ATDs are preferred.
  • GD diagnosed before pregnancy: ATDs may be stopped if asymptomatic and well-controlled.
  • ≤ 16 weeks' gestation: propylthiouracil ^[9][22]
  • > 16 weeks' gestation: methimazole or continue propylthiouracil ^[21][22]
  • Treatment goals: Keep the free T₄ level at or just above the upper limit of normal using the lowest possible dose of ATDs. ^[22]
  • Monitoring throughout pregnancy includes:
    • TFTs every 2–6 weeks ^[22]
    • TRAb titers (intervals vary) ^[22]
    • Prenatal ultrasounds (if TRAbs are elevated or uncontrolled maternal hyperthyroidism)
• Alternative: thyroidectomy
  • Indicated for refractory symptoms or the inability to take ATDs for GD
  • Safest in the second trimester
• Screening for neonatal GD is recommended for all infants born to mothers with GD.

Radioactive iodine ablation therapy is contraindicated during pregnancy. ^[9]

Differential diagnoses of hyperthyroidism in pregnancy

• Graves disease
• hCG-mediated hyperthyroidism
• Rare
  • Toxic adenoma
  • Toxic multinodular goiter
  • Thyroiditis
  • Iodine-induced hyperthyroidism
• See also “Common causes of hyperthyroidism.”

Consider gestational trophoblastic disease in patients presenting with severe hyperthyroidism, a positive pregnancy test, and no features of Graves disease. ^[22]

Complications ^[23]

• Fetus or newborn
  • Death: spontaneous abortion, stillbirth
  • Poor growth: IUGR, small for gestational age, low birth weight
  • Prematurity
  • Congenital conditions: malformations, thyroid disease ^[22]
• Pregnant individual
  • Hypertension
  • Premature labor
  • Heart failure
  • Thyroid storm

Uncontrolled hyperthyroidism is associated with both adverse fetal and maternal outcomes. ^[22]

• Epidemiology: Neonatal hyperthyroidism occurs in ∼ 5% of babies born to mothers with GD.
• Etiology: : transplacental passage of maternal TRAbs
• Clinical features
  • Hyperthyroidism: irritability, restlessness, tachycardia, diaphoresis, hyperphagia, poor weight gain, diffuse goiter (can cause tracheal compression), microcephaly (due to craniosynostosis)
  • May present directly after birth or be delayed for up to 10 days as a result of transplacental antithyroid medication (including propylthiouracil or carbimazole)
• Screening for neonatal hyperthyroidism:
  • Maternal TRAbs should be performed for all women with: ^[9]
    • Current GD
    • Previous GD if treated with RAIA or surgery
    • Previous pregnancy affected by neonatal hyperthyroidism
  • Screen all infants born to women with positive or unknown TRAbs during pregnancy. ^[27]
    • Measure cord blood at delivery for TRAbs; if negative, no further screening is required.
    • Measure TSH and free T4 at day 3–5 and again at day 10–14.
    • Folllow infants clinically until 2–3 months of age.
• Treatment
  • Usually resolves within 1–3 months
  • Infants with symptomatic hyperthyroidism: methimazole and propranolol ^[27]
• Complications: Untreated symptomatic hyperthyroidism in infants can cause cardiac failure and intellectual disability.

If fetal hyperthyroidism is suspected, involve a multidisciplinary care team, including maternal-fetal medicine, neonatology, and anesthesiology. ^[22]

GD is the most common cause of hyperthyroidism in children. ^[17]

Clinical features ^[9][17]

• Classic clinical features of GD are often less marked or variable in children and adolescents.
  • Goiter often vary in size.
  • Graves ophthalmopathy is typically milder than in adults.
  • Dermopathy is rare. ^[28]
• Additional symptoms
  • Behavioral problems
  • Poor performance in school
  • Emotional instability
  • Growth spurt with advanced bone age

Diagnostics ^[9][17]

• Diagnostics of GD is similar in children and adults.
• Because clinical features of GD are frequently absent, confirmatory studies for GD are often necessary. ^[9][17]
  • Initial confirmatory test: TRAb titers
  • If TRAb titers are normal: thyroid ultrasound ^[17]

In children with suspected GD, TRAb titers and thyroid ultrasound are generally preferred for diagnosis because of radiation exposure from RAIU. ^[17][29]

Treatment ^[9][17][29]

Treatment of GD is generally similar to adults, with some modifications.

• Preferred first-line treatment: trial of methimazole (MMI) ; ^[9]
  • If free T4, total T3, and TSH levels begin to normalize, continue treatment for at least 1–2 years. ^[9][21]
  • If there is no improvement in TFTs with MMI,; or if the medication is not tolerated, proceed to definitive treatment. ^[9][21]
• Definitive treatment (i.e., RAIA or thyroid surgery) is indicated if ATD therapy fails and may be used as initial treatment in patients with:
  • Contraindications to MMI
  • Low chance of remission with MMI ^[9][29]
  • Indications for thyroid surgery
• If considering definitive therapy, patient factors are used to determine the preferred modality.
  • RAIA is not recommended in children < 5 years; ; consider in patients 5–10 years of age. ^[9][17][29]
  • Surgery may be preferred over RAIA in patients with large goiters. ^[9][17]
• Lifelong monitoring with TFTs is necessary to:
  • Detect recurrence (e.g., for MMI therapy)
  • Monitor iatrogenic hypothyroidism (e.g., after RAIA or thyroid surgery)

Propylthiouracil is not recommended in children and adolescents because of an increased risk of liver injury. ^[9]

Clinical features ^[9][12][30]

• Clinical features of GD are similar in older adults and the general adult population.
• Older adults can present with fewer features or nonspecific symptoms, e.g.:
  • Weight loss
  • Shortness of breath
  • Atrial fibrillation ^[9][30]
  • Depression, lethargy (apathetic hyperthyroidism) ^[12][30][31]
• Medications taken for other conditions may mask symptoms of hyperthyroidism. ^[30][32]

Presentations of GD in older adults can be subtle; sometimes only a single symptom (e.g., atrial fibrillation) is present. ^[30]

Diagnostics ^[9][21][30]

• Diagnostics for GD are similar in older adults and the general adult population.
• Subclinical hyperthyroidism is more common than overt hyperthyroidism. ^[30]
• In patients with cardiac symptoms, consider: ECG, echocardiogram, Holter monitor, myocardial perfusion imaging. ^[9]

Treatment ^[9][21][30]

Management of GD is similar to the general adult population, with some modifications.

• Complications from thyrotoxicosis are common in older adults; symptomatic therapy for thyrotoxicosis is strongly recommended. ^[9]
• Manage any associated cardiovascular complications; including anticoagulation for Afib. ^[9][30]
• ATD therapy with MMI or RAIA is generally preferred over surgery. ^[9][30]
  • Definitive therapy is recommended in individuals with cardiovascular complications due to hyperthyroidism. ^[9][12][21]
  • For patients undergoing RAIA, prophylactic use of ATDs for GD and symptomatic therapy for thyrotoxicosis is recommended. ^[9]