What is the management of Graves' disease with exophthalmos that is refractory to antithyroid drugs (ATD) after 10 months?

From the Guidelines

For question 22, the recommended management is total thyroidectomy (option A), as this patient has persistent hyperthyroidism despite being prescribed medication, as evidenced by the suppressed TSH level of 0.2 and symptoms of palpitations and tachycardia. Total thyroidectomy is preferred for toxic nodular goiter with poor medication compliance because it provides definitive treatment, eliminating the need for long-term medication adherence. Unlike Graves' disease, toxic nodular goiter rarely goes into remission with medical therapy alone, making surgery a more appropriate option for long-term control.

Some key points to consider in the management of toxic nodular goiter include:

• The importance of achieving definitive treatment to prevent long-term complications of hyperthyroidism
• The role of surgery in providing a cure for the condition
• The need for lifelong thyroid hormone replacement therapy after surgery

For question 23, the recommended management is near total thyroidectomy (option B), as Graves' disease with exophthalmos that is not responding to antithyroid drugs for 10 months requires a more definitive treatment approach. Near total thyroidectomy removes most of the thyroid tissue while minimizing the risk of complications such as hypoparathyroidism and recurrent laryngeal nerve injury. Following surgery, the patient will require lifelong thyroid hormone replacement therapy. The use of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, may also be considered in the management of Graves' disease with exophthalmos, as it has been shown to reduce proptosis and the clinical activity score of disease in many patients with active disease 1. However, its use is not universally available and is associated with a number of adverse reactions.

Some key points to consider in the management of Graves' disease with exophthalmos include:

• The importance of achieving definitive treatment to prevent long-term complications of hyperthyroidism and exophthalmos
• The role of surgery in providing a cure for the condition
• The potential benefits and risks of using teprotumumab in the management of Graves' disease with exophthalmos
• The need for lifelong thyroid hormone replacement therapy after surgery
• The importance of consultation with an orbital disease specialist in patients with concurrent proptosis and significant strabismus 1

From the Research

Management of Toxic Nodular Goiter

• The patient has a history of toxic nodular goiter and is experiencing palpitations and tachycardia with a TSH level of 0.2, indicating hyperthyroidism.
• According to the study by 2, surgical treatment results in rapid, reliable resolution of hyperthyroidism and removal of the nodular goiter with low morbidity and no mortality.
• The study by 3 suggests that thyroidectomy or radioiodine therapy is recommended for managing hyperthyroidism due to toxic nodular goiter, with concern for concomitant malignancy favoring surgery.
• The study by 4 compares surgical techniques for treatment of benign toxic multinodular goiter and finds that total thyroidectomy (TT) and near-total thyroidectomy (NTT) are safe and effective approaches, preventing recurrence of thyrotoxicosis and reoperation for incidentally found thyroid cancers.

Management Options

• Total thyroidectomy (TT) is a recommended treatment option for toxic nodular goiter, as it results in rapid and reliable resolution of hyperthyroidism and removal of the goiter.
• Near-total thyroidectomy (NTT) is also a viable option, as it is similarly effective to TT but may be considered safer.
• Subtotal thyroidectomy (ST) may not be the best option, as it may leave an undetected thyroid cancer in place and has a higher rate of goiter recurrence compared to TT.

Graves' Disease with Exophthalmos

• For Graves' disease with exophthalmos that is not responding to antithyroid drugs, the management options include:

• Near-total thyroidectomy, as it is a recommended treatment option for Graves' disease that is not responsive to medical therapy.
• Radioiodine therapy, which is a safe and effective treatment option for Graves' disease.

• The study by 2 suggests that surgical treatment is a viable option for patients with Graves' disease who are not responsive to medical therapy.
• The study by 5 compares TT and ST for multinodular non-toxic goitre and finds that TT reduces goiter recurrence, but the effects on other key outcomes such as re-interventions due to goitre recurrence, adverse events, and thyroid cancer incidence are uncertain.
• The study by 6 approaches the patient with nontoxic multinodular goiter and suggests that patients with nodules yielding malignant cytology should be referred for surgery, and patients with benign but large goiters may experience clinical symptoms of pressure and require surgery for alleviation of symptoms.