This patient should undergo thyroidectomy to treat his obstructive substernal goiter and prevent further airway compromise, which may be rapid and fatal. The thyroid nodule biopsy findings obtained 5 years ago most likely represent adenomatous hyperplasia, and the sonographic features of the gland and slow progression of the compressive symptoms support a diagnosis of a benign lesion. He has evidence of compressive symptoms on physical examination, with facial flushing when raising his arms (Pemberton sign). The flushing indicates venous outflow obstruction by the goiter as the vessels course through the thoracic inlet. Additionally, his symptoms of dysphagia and change in voice quality may suggest a compressive effect on the esophagus and recurrent laryngeal nerves, respectively. Surgical removal of the thyroid offers the best option for immediate relief of symptoms and identification of a possible underlying malignancy.

External-beam radiotherapy can result in eventual shrinkage of the thyroid but will not provide immediate relief of his obstructive symptoms, is unlikely to be curative, potentially increases the risk of secondary malignancy, and is associated with significant morbidity.

Levothyroxine therapy has been shown to reduce thyroid volume by up to 20%, but the clinical significance of this small change in volume with such a large goiter is unlikely to improve symptoms. Additionally, levothyroxine therapy may take many months to years to reduce the thyroid volume, and this patient needs immediate relief of his obstructive symptoms.

Radioactive iodine has been used to shrink multinodular goiters; the volume change is also gradual and optimal reduction averages 40%. However, radioactive iodine therapy may be risky in this patient because acute swelling of the thyroid after iodine uptake can lead to compromise of the vascular structures at the level of the thoracic inlet and further compression of the trachea.