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Graves' disease

Background

Overview

Definition
GD is a systemic autoimmune disease characterized by the production of antibodies against TSH receptors.
1
Pathophysiology
GD is caused by autoimmunity rendered by complex interactions between genetic (75-80%) and environmental factors (20-25%).
1
Epidemiology
The annual incidence of GD is estimated at 20-30 cases per 100,000 persons; lifetime risk for women and men is approximately 3% and 0.5%, respectively.
2
Disease course
The overproduction of thyroid hormone is caused by thyroid-stimulating immunoglobulins via thyrotropin receptor activation, which results in hypertrophy and hyperplasia of the gland. In addition, the production of cytokines by infiltrating immune cells results in inflammation and altered thyroid cell behavior. The orbital infiltration of immune cells, activation of thyrotropin-insulin-like growth factor 1 receptor complex, signaling of orbital fibroblasts, and adipogenesis results in orbital tissue expansion, proptosis, and optic nerve compression. Diffuse goiter, ophthalmopathy, dermopathy, alteration in mental status, and cardiac complications may ensue.
3
Prognosis and risk of recurrence
Anti-thyroid drug therapy is associated with 40-50% remission after 12-18 months of treatment.
2

Guidelines

Key sources

The following summarized guidelines for the evaluation and management of Graves' disease are prepared by our editorial team based on guidelines from the American Diabetes Association (ADA 2024), the European Thyroid Association (ETA 2022,2018), and the American Thyroid Association (ATA 2016). ...
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Screening and diagnosis

Indications for screening
As per ADA 2024 guidelines:
Consider screening for antithyroid peroxidase and anti-TG antibodies soon after diagnosis in pediatric patients with T1DM.
C
Measure TSH concentrations at diagnosis when clinically stable or soon after optimizing glycemia. Consider rechecking every 1-2 years or sooner if the initial screening is normal in young patients with positive thyroid antibodies or developing symptoms or signs suggestive of thyroid dysfunction, thyromegaly, an abnormal growth rate, or unexplained glycemic variability.
B
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Diagnostic investigations

Thyrotropin receptor antibodies
As per ETA 2018 guidelines:
Obtain TSH receptor autoantibodies for rapid and accurate diagnosis and differential diagnosis of GD.
A
Consider differentiating TSH receptor autoantibodies functionality, when technically available, as it is helpful and predictive in patients with GD during pregnancy/postpartum and for extrathyroidal manifestations.
C

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  • Baseline laboratory tests

  • Diagnostic imaging

Medical management

Antithyroid drugs: as per ETA 2018 guidelines, initiate antithyroid drugs in patients with newly diagnosed GD.
A
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  • Beta-blockers

  • Radioactive iodine

  • Antihistamines

  • Management of thyroid storm

  • Management of subclinical hyperthyroidism

Nonpharmacologic interventions

Smoking cessation: as per ATA 2016 guidelines, advise smoking cessation in patients with GD and refer them to a structured smoking cessation program. Identify patients exposed to secondhand smoke and advise of its negative impact, as both firsthand and secondhand smoking increase Graves' orbitopathy risk.
B

Perioperative care

Preoperative care: as per ETA 2018 guidelines, restore euthyroidism by antithyroid drugs before surgery to avoid peri- or postoperative exacerbation of thyrotoxicosis.
A
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  • Postoperative care

Surgical interventions

Thyroidectomy
As per ETA 2018 guidelines:
Consider performing thyroidectomy in patients with newly diagnosed GD preferring this approach.
B
Perform total thyroidectomy as the procedure of choice by a skilled surgeon with high annual volumes of thyroidectomies, if surgery is selected.
A

Specific circumstances

Pediatric patients, evaluation: as per ETA 2022 guidelines, obtain WBC count including neutrophil count and liver function tests at baseline as both can be affected by the underlying disease process and antithyroid drug therapy.
B

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  • Pediatric patients (antithyroid drugs)

  • Pediatric patients (beta-blockers)

  • Pediatric patients (radioactive iodine)

  • Pediatric patients (immunomodulators)

  • Pediatric patients (thyroidectomy)

  • Pediatric patients (treatment monitoring)

  • Pediatric patients (management of thyroid nodules)

  • Pediatric patients (management of orbitopathy)

  • Elderly patients

  • Pregnancy planning

  • Pregnant patients (evaluation)

  • Pregnant patients (antithyroid drugs)

  • Pregnant patients (thyroidectomy)

  • Breastfeeding

  • Patients with immune reconstitution

  • Patients with orbitopathy

Follow-up and surveillance

Treatment monitoring
As per ETA 2018 guidelines:
Inform patients about the potential side effects of antithyroid drugs and the necessity of informing the physician promptly if they develop jaundice, light-colored stools, dark urine, fever, pharyngitis, or cystitis.
B
Obtain a differential WBC count in patients taking antithyroid drugs during febrile illness and/or pharyngitis. Assess liver function in patients experiencing jaundice, light-colored stools or dark urine.
B

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  • Management of refractory disease