With Takashi Akamizu, MD, PhD, Peter Kopp, MD, and Elizabeth Pearce, MD, MSc
Thyroid storm, or thyrotoxic crisis, is a rare but life-threatening form of hypermetabolic thyrotoxicosis with tachycardia and other cardiac symptoms. With a mortality rate estimated at greater than 10%, the condition demands a rapid diagnosis and initiate treatment immediately, as physicians are well aware.1
However, despite the appearance of the term ''thyroid storm'' in medical literature since the late 1920s, its incidence remains poorly defined,1 according to Takashi Akamizu, MD, PhD, professor of medicine at Wakayama Medical University in Japan. Debate on optimal treatment strategies continues as well.
In response to this need for a more consistent approach to clinical care, Dr. Akamizu introduced updating the guidelines for Thyroid Storm,2 which were published in Thyroid. While not an original study, said Peter Kopp, MD, editor-in-chief of the journal and professor of medicine at Northwestern University' Feinberg School of Medicine, it is a well-conceived review article on the Japanese experience with thyroid storm, including recent research and hospital surveys, available since the Japanese guidelines on thyroid storm were presented in 2016.
"The value of this effort is that the proposed management changes better define what thyroid storm is, and he gives helpful practice recommendations that are somewhat simplified in comparison to what we did historically," Dr. Kopp told EndocrineWeb, "For instance, iodine is typically only given after antithyroid medicines; the Japanese team says they can be given simultaneously."
Even so, "I prefer recommendations [as the preferred term to use] rather than guidelines," said Dr. Kopp, because much of the information on thyroid storm is based not on scientific, randomized studies but on anecdotal experiences that lead to practice patterns.
"It's a very vexing clinical entity," he said of Thyroid Storm, so the review is a step forward; however, these recommendations are not written in stone, of course, and will be subject to change as more information becomes available.
Certainly, these proposed changes to the treatment guidelines are fluid, the value remains, said Dr. Akamizu, since they are evidence-based, deeply detailed, and provide illustrated algorithms,2 they are thought to be very practical and clinically useful," Dr. Akamizu told EndocrineWeb; “however, we plan to initiate a prospective study to validate the proposed guidelines.”
Even so, he anticipates some resistance to these new recommendations,2 which differ somewhat from the 2016 American Thyroid Association (ATA) guidelines, 1 and the 2016 Japanese treatment guidelines3 for which Dr. Akamizu was the senior author.
"Although our work has been formally endorsed by both American and European Thyroid Associations, the proposed changes may raise some controversies," said Dr. Akamizu.
He highlighted three specific differences between his team’s proposed changes to current practice and the ATA guidelines.1,2
Of most interest to clinicians, Dr. Akamizu said, is what has been "common sense in the treatment of thyroid storm is being challenged," to better reflect recent patient outcomes. For example, "iodine may be administered simultaneously with antithyroid medication, and MMI may be used as first-line treatment of thyroid store caused by Graves' disease."
The diagnostic criteria were developed with information from 99 patients in the medical literature and 7 in the Japanese study.4 Surveys began in 2004 and continued through 2008, targeting all hospitals in Japan.4 Based on this data, the diagnostic criteria were revised and management and treatment guidelines were developed to more closely model patient experiences.
Dr. Akamizu and his team found an incidence of thyroid storm of 0.20 per 100,000 per year in 22% of all thyrotoxic patients.2 Mortality rate was 10.7%. Cause of death was most often multiple organ failure, followed by congestive heart failure, respiratory failure, and arrhythmia.
In the final diagnostic criteria for thyroid storm, the definition of jaundice as serum bilirubin concentration more than 3 mg/dL was added.2
As multiple organ failure is common, the care must be provided by a multidisciplinary team, including an endocrinologist, cardiologist, neurologist, and hematologist, according to our guidelines,2 Dr. Akamizu and his colleagues.
As for treatment targets, there are five pressing clinical concerns:2
The proposed guidelines include 15 recommendations for the treatment of thyrotoxicosis and organ failure, but due to space limitations, Dr. Akamizu included only treatment for hyperthyroidism due to Graves' disease, tachycardia, and congestive heart failure. The full guideline published in Endocrine Journal includes all the recommendations.3
For thyrotoxicosis due to Graves, the guidelines suggest a multidisciplinary approach with ATDs, inorganic iodide, corticosteroids, beta-AAs and antipyretic agents. ATDs, either MMI or PTU should be used for hyperthyroidism in thyroid storm, based on the Japanese guidelines.3
According to the report, the ATA guidelines recommend PTU because large doses inhibit type 1 deiodinase activity and may decrease T3 levels more than MMI. However, he cites research showing no mortality or disease severity differences between treatment with MMI or PTU.
Under the Japanese guidelines,4 inorganic iodide should be used concurrently with ATD to those with thyroid storm caused by thyrotoxic diseases associated with hyperthyroidism.3 In contrast, the ATA guidelines recommend iodide be given an hour after ATDs.1 In the report, research is cited that found combining the two normalizes thyroid hormones more quickly.2
Dr. Akakiza said, the proposed new guidelines, beta-1 selective adrenergic antagonists, such as landiolol, would be first-line agents to treat tachycardia in thyroid storm.3 Propranolol is not contraindicated but is not recommended for tachycardia in thyroid storm patients with congestive heart failure. The use of non-selective beta-AAs, especially propranolol, warrants caution, he said.
The new Japanese guidelines are of value, said Elizabeth Pearce, MD, associate professor of medicine, Boston University Medical Center and Boston University School of Medicine, who reviewed the study and proposed guidelines for EndocrineWeb.
That is because ''thyroid storm is an extremely rare condition, prospective data are sparse, and the underlying pathogenesis and optimal treatment strategies are still largely unknown," said Dr. Pearce. For instance, the new report has shed light on the annual incidence—two per 1,000,000.2
"Mortality was just over 10%, an improvement from older estimates, which was likely due to enhanced techniques for the management of critically ill patients, but still high," she said, and another important point is that thyroid storm remains a clinical diagnosis, as thyroid biochemistry does not correlate with disease severity.
While the proposed Japanese guidelines and the ATA guidelines do not line up exactly,1,2 they are in agreement, said Dr. Pearce, particularly with regard to the ''mainstay of therapy include a multidisciplinary approach and treatment with antithyroid drugs, inorganic iodide, glucocorticoids, and beta-blockade."
The planned study to validate the recommendation certainly will provide clinically important validation, she said.
None of the physicians reported any financial conflicts.
Ross, DS, Burch HB, Copper 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.
Akamizu T. Thyroid Storm: A Japanese Perspective. Thyroid. 2017. Ahead of Print. Available at: http://online.liebertpub.com/doi/full/10.1089/thy.2017.0243. Accessed January 3, 2018.
Satoh T, Isozaki O, Suzuki A, et al, for the Japan Thyroid Association and Japan Endocrine Society Taskforce Committee for the establishment of diagnostic criteria and nationwide surveys for thyroid storm. 2016 Guidelines for the management of thyroid storm from the Japan Thyroid Association and Japan Endocrine Society (1st ed). Endocr J. 2016;63(12):1025-1064.
Akamizu T, Satoh T, Isozaki O, Suzuki A, Wakino S, et al. Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys. Thyroid. 2012; 22: 661-679.