Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys

Abstract

Background: Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively.

Methods: We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2.

Results: We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3 mg/dL.

Conclusions: TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.

FIG. 1.

Duration until the onset of thyroid storm in SURVEY-2. The duration between the initial diagnosis of Graves' disease and the onset of thyroid storm is summarized in the upper panel. The number of patients who developed thyroid storm within one year after the initial diagnosis of underlying thyroid disease is shown in the lower panel. SURVEY-2, The Second Nationwide Survey.

FIG. 2.

Relationship between (A) FT4 and (B) FT3 levels and TSH in patients with TS1 and TS2 as obtained in SURVEY-2. Dashed lines show the limits of reference ranges. One TS1 case whose FT4 level was normal had a suppressed TSH and an elevated FT3 level, indicating a thyrotoxic state (an arrow). Six TS1 patients with normal FT3 levels had increased FT4 levels and suppressed TSH levels, being diagnosed as thyrotoxic. FT4, free thyroxine; FT3, free triiodothyronine; TSH, thyrotropin; TS, thyroid storm.

FIG. 3.

Distribution of body temperature in patients with TS1 (n=272) and TS2 (n=71). The dashed line indicates the cut-off value for our diagnostic criteria (≥38°C).

FIG. 4.

Distribution of heart rate in patients with TS1 (n=276) and TS2 (n=71). The dashed line indicates the cut-off values in our criteria (≥130 bpm).

FIG. 5.

Distribution of (A) GCS and (B) JCS scores in patients with TS1 (GCS, n=207; JCS, n=249) and TS2 (GCS, n=47; JCS, n=61). The dashed lines indicate the cut-off values in our criteria (GCS≤14, JCS≥1). GCS, Glasgow Coma Scale; JCS, Japan Coma Scale.

FIG. 6.

(A) NYHA and (B) Killip classifications of CHF in patients with TS1 (n=140) and TS2 (n=38). The dashed bars indicate the cut-off values in our criteria (NYHA≥4, Killip≥3). NYHA, New York Heart Association; CHF, congestive heart failure.

FIG. 7.

Possible factors contributing to the severity and prognosis of thyroid storm. DIC, disseminated intravascular coagulation; MOF, multiple organ failure.