What is the pathophysiology and management of a patient presenting with diffuse goiter, exophthalmos, and hyperthyroidism?

From the Guidelines

The patient's condition is most likely caused by stimulatory TSH antibodies, which are a hallmark of Graves' disease, an autoimmune disorder characterized by diffuse goiter, exophthalmos, and hyperthyroidism. The pathophysiology involves autoantibodies called thyroid-stimulating immunoglobulins (TSI) that bind to thyroid-stimulating hormone (TSH) receptors, causing unregulated thyroid hormone production 1. Management includes:

• Antithyroid medications such as methimazole (starting at 10-30 mg daily) or propylthiouracil (100-300 mg daily in divided doses), which inhibit thyroid hormone synthesis.
• Beta-blockers like propranolol (40-120 mg daily in divided doses) can provide symptomatic relief from tachycardia and tremors 2.
• Definitive treatment options include radioactive iodine therapy (typically 10-15 mCi of I-131) or thyroidectomy. For exophthalmos, lubricating eye drops, elevation of the head while sleeping, and in severe cases, glucocorticoids or orbital decompression surgery may be necessary 3. Regular monitoring of thyroid function tests is essential, with dose adjustments based on response. Antithyroid medications are typically continued for 12-18 months before attempting discontinuation. Patients should be counseled about potential side effects including agranulocytosis with antithyroid drugs and the likely need for lifelong levothyroxine replacement following definitive treatment with radioactive iodine or surgery.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Pathophysiology of Diffuse Goiter and Exophthalmos

The patient's presentation of diffuse goiter and exophthalmos is consistent with Graves' disease, an autoimmune disorder that causes hyperthyroidism 4, 5. The pathophysiology of this condition involves:

• The production of thyroid-stimulating antibodies (TSAb) that stimulate the thyroid gland to produce excess thyroid hormones 4
• The activation of T helper (Th)1 immune response, which plays a key role in the immune-pathogenesis of Graves' disease and its extrathyroidal manifestations, such as Graves' ophthalmopathy (GO) 4
• The stimulation of the thyroid gland by TSAb, leading to an increase in thyroid hormone production and release 6, 5

Management of Hyperthyroidism

The management of hyperthyroidism due to Graves' disease involves:

• Antithyroid medications, such as methimazole and propylthiouracil, to reduce thyroid hormone production 6, 7
• Radioactive iodine ablation of the thyroid gland, which is the most widely used treatment in the United States 6
• Surgical thyroidectomy, which may be considered in certain cases 6, 5
• Treatment of extrathyroidal manifestations, such as GO, with medications like rituximab and teprotumumab 4

Answer to the Question

Based on the evidence, the correct answer is: b. Stimulatory TSH antibodies, as the pathophysiology of Graves' disease involves the production of TSAb that stimulate the thyroid gland to produce excess thyroid hormones 4. T lymphocyte stimulation is also involved in the immune-pathogenesis of Graves' disease, but it is not the primary mechanism underlying the production of excess thyroid hormones 4.