From the Guidelines
The pathophysiology of the condition characterized by diffuse goiter and exophthalmos is primarily due to stimulatory TSH antibodies, which is a hallmark of Graves' disease, an autoimmune disorder where antibodies called thyroid-stimulating immunoglobulins (TSIs) bind to thyroid-stimulating hormone (TSH) receptors, causing excessive thyroid hormone production. This results in hyperthyroidism, diffuse goiter, and often exophthalmos (bulging eyes) due to inflammation of orbital tissues. The most recent and highest quality study, 1, although focused on immune-related adverse events in patients treated with immune checkpoint inhibitor therapy, highlights the importance of recognizing Graves' disease through physical examination findings of ophthalmopathy or thyroid bruit, which are diagnostic and should prompt early endocrine referral.
Pathophysiology and Clinical Presentation
The condition is characterized by:
- Hyperthyroidism due to autoimmune stimulation of the thyroid gland
- Diffuse goiter
- Exophthalmos (bulging eyes) due to inflammation of orbital tissues
- Symptoms of hyperthyroidism, such as tremors, nervousness, insomnia, excessive sweating, heat intolerance, tachycardia, hypertension, and goiter, as noted in 1
Treatment Approach
Treatment typically follows a three-pronged approach:
- First-line therapy usually involves antithyroid medications such as methimazole or propylthiouracil, which block thyroid hormone synthesis, as discussed in 1
- Beta-blockers like propranolol are added to control symptoms such as tachycardia and tremors
- For definitive treatment, radioactive iodine (RAI) therapy or total thyroidectomy may be performed, with most patients requiring lifelong thyroid hormone replacement after RAI or surgery, typically with levothyroxine, as is standard practice and supported by the principles outlined in 1 and 1
Considerations for Exophthalmos
For exophthalmos, treatment may include:
- Lubricating eye drops
- Selenium supplements
- In severe cases, glucocorticoids or orbital decompression surgery may be necessary, as part of managing the autoimmune and inflammatory aspects of Graves' disease, in line with the approach to managing immune-related adverse events 1.
From the FDA Drug Label
In patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate treatment option. Patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter who are intolerant of methimazole and for whom surgery or radioactive iodine therapy is not an appropriate treatment option.
The pathophysiology of this condition is related to autoimmune stimulation of the thyroid gland, specifically Graves' disease. The correct answer is b. Stimulatory TSH antibodies, as Graves' disease is characterized by the presence of stimulatory TSH receptor antibodies that activate the TSH receptor, leading to increased thyroid hormone production and hyperthyroidism. 2 3
From the Research
Pathophysiology of Graves' Disease
The pathophysiology of Graves' disease is characterized by:
- Autoimmune stimulation of the thyroid gland, leading to hyperthyroidism 4, 5
- Infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues 4
- Stimulatory autoantibodies (Ab) that activate the TSH-R, leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion 4
- T lymphocyte stimulation is not the primary cause, but rather a component of the autoimmune response 4
- The correct answer is b. Stimulatory TSH antibodies, as they play a key role in the pathogenesis of Graves' disease 4, 5
Treatment of Graves' Disease
The treatment of Graves' disease includes:
- Antithyroid medications, such as methimazole (MMI) and propylthiouracil, to decrease thyroid hormone synthesis 4, 6, 7, 5
- Radioactive iodine (RAI) treatment to reduce the amount of thyroid tissue 4, 6, 7, 5
- Total thyroidectomy, which should be performed by an experienced high-volume thyroid surgeon 4, 7
- Non-thionamide antithyroid drug options, such as iodine compounds and potassium perchlorate, may be considered in patients who are intolerant or unresponsive to thionamides alone 8
- Treatment choices should be individualized and patient-centered, taking into account the underlying diagnosis, presence of contraindications, severity of hyperthyroidism, and patient preference 4, 6, 7, 5