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Thionamide Smackdown – PTU vs MMI for Thyroid Storm

May 9, 2023

Written by Sam Parnell

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This comparative effectiveness study showed no significant difference in clinical outcomes or adverse effects when comparing use of propylthiouracil (PTU) and methimazole (MMI) for thyroid storm. This suggests both medications may be reasonable first-line treatment options for patients with thyroid storm.

Why does this matter?
Thyroid storm is a rare, life-threatening condition that can lead to neurologic impairment, hepatic dysfunction, and cardiovascular collapse. It is associated with significant morbidity and mortality, so rapid recognition and management is essential. Patients with thyroid storm are frequently treated with beta blockers, thionamides, iodine, glucocorticoids, and cholestyramine. Propylthiouracil (PTU) and methimazole (MMI) are the two most commonly used thionamides. However, the choice of thionamide is slightly contentious. Previous studies have shown PTU may decrease T4 to T3 conversion more than MMI, and the 2016 American Thyroid Association (ATA) guidelines recommend PTU as first-line therapy for thyroid storm.1,2 On the other hand, MMI has a longer duration of action and may have less hepatotoxicity compared to PTU. In Japan, MMI is preferred, and the Japan Thyroid Association guidelines recommend both PTU and MMI as first-line treatment based on a retrospective study of 356 patients that showed no difference in mortality or disease severity in patients who received MMI vs PTU.3

Thunderbolt and lightning, Thyroid storm is frightening!
This was a comparative effectiveness study utilizing a large, multicenter cohort from the US Premier Healthcare Database from January 2016 to December 2020. Adult patients with an ICD-10 diagnosis of thyroid storm who were admitted to an intermediate care unit or ICU and who received both corticosteroids and thionamides were included.

A total of 1383 patients were included, of which 656 patients (47.4%) received PTU and 727 patients (52.6%) received MMI. The primary outcome of in-hospital mortality or discharge to hospice was 7.4% overall, and there was no significance difference in mortality when comparing patients who received PTU vs MMI (8.5% PTU [56/656; 95%CI, 6.4%-10.7%] vs 6.3% MMI [46 of 727; 95% CI, 4.6%-8.1%]). There were no significant differences in hospitalization costs, duration of organ support, or adverse events. Furthermore, subgroup analyses showed no difference in mortality between the exposure groups.

This study did have a few limitations. It was retrospective, based on claims data, and there was no rationale listed for why patients were initially treated with MMI or PTU. Furthermore, the median dose of methimazole on study day 0 was 40 mg (IQR, 20-60 mg), which is lower than the ATA recommended dose of 60 to 80 mg. This deviance from clinical guidelines could be due to undertreatment of thyroid storm or less severe thyroid storm in MMI patients.

Thyroid storm is a rare disease, so developing a large, prospective, randomized controlled trial is extremely challenging. This study was not perfect, but it is the largest study to date comparing mortality of patients based on thionamide treatment regimen. These results suggest PTU and MMI are both reasonable first-line options for thyroid storm.

Comparison of Propylthiouracil vs Methimazole for Thyroid Storm in Critically Ill Patients. JAMA Netw Open. 2023 Apr 3;6(4):e238655. doi: 10.1001/jamanetworkopen.2023.8655.

Works Cited

  1. Abuid J, Larsen PR. Triiodothyronine and thyroxine in hyperthyroidism: comparison of the acute changes during therapy with antithyroid agents. J Clin Invest. 1974;54(1):201-208. doi:10.1172/JCI107744
  2. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343-1421. doi:10. 1089/thy.2016.0229
  3. Isozaki O, Satoh T, Wakino S, et al. Treatment and management of thyroid storm: analysis of the nationwide surveys: the taskforce committee of the Japan Thyroid Association and Japan Endocrine Society for the establishment of diagnostic criteria and nationwide surveys for thyroid storm. Clin Endocrinol (Oxf). 2016;84(6): 912-918. doi:10.1111/cen.12949

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