Novel triple-drug regimen for preoperative optimization in giant Graves' disease: a prospective efficacy and safety...

Graves' disease (GD) is a major cause of hyperthyroidism worldwide. Although most patients with GD achieve remission following treatment with anti-thyroid drugs (ATDs) or radioiodine (¹³¹I) therapy, a subset of individuals experience ongoing disease progression, presenting with refractory hyperthyroidism and marked thyroid enlargement (thyroid volume ≥100 mL, even several hundred milliliters in severe cases). We refer to GD with this clinical phenotype as "giant" GD. Total thyroidectomy is the preferred definitive treatment for these patients, but it is technically challenging and carries higher perioperative risk. Evidence-based preoperative management strategies for this condition remain limited. This study aimed to evaluate the efficacy and safety of a novel triple-drug preoperative preparation regimen in patients with "giant" GD.

Thirteen patients with "giant" GD scheduled for total thyroidectomy were treated with methimazole (MMI) followed by combined MMI and levothyroxine (LT4) to achieve euthyroidism. After the surgical date was scheduled, an oral compound iodine solution was administered at three drops per dose three times daily on day 1, with the dose increased by one drop per administration on each subsequent day (e.g., four drops three times daily on day 2, five drops three times daily on day 3), ultimately reaching 16 drops per dose. Primary outcome was euthyroidism [normal free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) levels] at surgery. Secondary outcomes included changes in thyroid volume, superior thyroid artery peak systolic velocity (PSV), clinical parameters, operative blood loss, complications, and drug-related adverse events.

A total of 13 patients (9 women and 4 men), aged 19-78 years, were enrolled. The median baseline thyroid volume was 307.66 mL, which decreased to 283.68 mL following preoperative preparation. The PSV of the superior thyroid artery showed a marked reduction in all patients, ranging from 1.78% to 63.64%. Thyroid hormone levels also declined, with FT4 decreasing from 21.5-(>100) to 12.37-19.3 pmol/L and FT3 from 8.02-31.8 to 4.10-7.46 pmol/L. Basal metabolic rate (BMR) decreased from 28-60% to -11% to 16%. The operative time ranged from 120 to 270 minutes, and the median intraoperative blood loss was 77.7 mL. Significant improvement was observed in symptoms of severe hyperthyroidism, and partial relief was noted in selected extrathyroidal manifestations.

These findings demonstrate the clinical efficacy and safety of a triple-drug preoperative preparation regimen in patients with "giant" GD. This strategy effectively reduces surgical difficulty and perioperative risk, contributing to safer and more efficient management. Incorporation of this regimen into preoperative protocols for "giant" GD may help optimize patient outcomes and surgical success.