Iopanoic Acid in Severe Thyrotoxicosis: Rediscovering an Effective Therapy.

Abstract

Background: Severe thyrotoxicosis remains a high-risk endocrine emergency, particularly in thyroid storm and amiodarone-induced thyrotoxicosis (AIT), where morbidity and mortality remain substantial despite modern intensive care. Rapid reduction of circulating triiodothyronine (T3) is central to stabilization, yet conventional therapies are often slow, unpredictable, or ineffective, particularly in iodine-replete states such as AIT.

Summary: We reviewed mechanistic, pharmacokinetic and clinical evidence for iopanoic acid, a potent inhibitor of type I and type II 5'-deiodinase that produces rapid, reversible suppression of peripheral thyroxine (T4) to T3 conversion, alongside comparative rescue strategies including Lugol's iodine, perchlorate, lithium, cholestyramine and therapeutic plasma exchange. Across early clinical studies and a contemporary tertiary-center case series, short-course iopanoic acid consistently produced large, rapid reductions in serum T3, typically within 24-48 hours, with parallel clinical improvement. In a recent series of 12 patients with treatment-resistant thyrotoxicosis, mean free T3 fell by approximately 55%, normalizing within a median of 2 days and enabling progression to definitive surgery in most cases. Reported use extends beyond thyroid storm to urgent pre-operative preparation of uncontrolled hyperthyroidism, amiodarone-induced thyrotoxicosis and destructive thyroiditis. Adverse effects are uncommon and generally mild, and withdrawal from routine clinical use reflects the obsolescence of oral cholecystography rather than safety concerns.

Conclusions: Iopanoic acid offers safe, rapid and predictable T3 reduction as short-course rescue or bridging therapy in thyroid storm and refractory, iodine-unresponsive AIT, where it can be lifesaving. It is not recommended for straightforward thyrotoxicosis. We synthesize the evidence into a pragmatic, protocol-based framework and argue that reliable, appropriately governed sourcing is now the principal barrier to its use.