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.


Importance: Thyroid storm is the most severe form of thyrotoxicosis, with high mortality, and is treated with propylthiouracil and methimazole. Some guidelines recommend propylthiouracil over methimazole, although the difference in outcomes associated with each treatment is unclear.

Objective: To compare outcomes associated with use of propylthiouracil vs methimazole for the treatment of thyroid storm.

Design, setting, and participants: This comparative effectiveness study comprised a large, multicenter, US-based cohort from the Premier Healthcare Database between January 1, 2016, and December 31, 2020. It included 1383 adult patients admitted to intensive or intermediate care units with a diagnosis of thyroid storm per International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and treated with either propylthiouracil or methimazole. Analyses were conducted from July 2022 to February 2023.

Exposure: Patients received either propylthiouracil or methimazole for treatment of thyroid storm. Exposure was assigned based on the initial thionamide administered.

Main outcomes and measures: The primary outcome was the adjusted risk difference of in-hospital death or discharge to hospice between patients treated with propylthiouracil and those treated with methimazole, assessed by targeted maximum likelihood estimation.

Results: A total of 1383 patients (656 [47.4%] treated with propylthiouracil; mean [SD] age, 45 [16] years; 473 women [72.1%]; and 727 [52.6%] treated with methimazole; mean [SD] age, 45 [16] years; 520 women [71.5%]) were included in the study. The standardized mean difference for age was 0.056, and the standardized mean difference for sex was 0.013. The primary composite outcome occurred in 7.4% of of patients (102 of 1383; 95% CI, 6.0%-8.8%). A total of 8.5% (56 of 656; 95% CI, 6.4%-10.7%) of patients who initiated propylthiouracil and 6.3% (46 of 727; 95% CI, 4.6%-8.1%) who initiated methimazole died in the hospital (adjusted risk difference, 0.6% [95% CI, -1.8% to 3.0%]; P = .64). There were no significant differences in duration of organ support, total hospitalization costs, or rates of adverse events between the 2 treatment groups.

Conclusion and relevance: In this comparative effectiveness study of a multicenter cohort of adult patients with thyroid storm, no significant differences were found in mortality or adverse events in patients who were treated with propylthiouracil or methimazole. Thus, current guidelines recommending propylthiouracil over methimazole for treatment of thyroid storm may merit reevaluation.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antithyroid Agents / therapeutic use
  • Critical Illness
  • Female
  • Hospital Mortality
  • Humans
  • Methimazole* / therapeutic use
  • Middle Aged
  • Propylthiouracil / therapeutic use
  • Thyroid Crisis* / drug therapy


  • Methimazole
  • Propylthiouracil
  • Antithyroid Agents