Thyroid Storm
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Thyroid storm, also referred to as thyrotoxic crisis, is an acute, life-threatening, hypermetabolic state induced by excessive release of thyroid hormones (THs) in individuals with thyrotoxicosis. Thyroid storm may be the initial presentation of thyrotoxicosis in undiagnosed children, particularly in neonates. The clinical presentation includes fever, tachycardia, hypertension, and neurological and GI abnormalities. Hypertension may be followed by congestive heart failure that is associated with hypotension and shock. Because thyroid storm is almost invariably fatal if left untreated, rapid diagnosis and aggressive treatment are critical. Fortunately, this condition is extremely rare in children.
Diagnosis is primarily clinical, and no specific laboratory tests are available. Several factors may precipitate the progression of thyrotoxicosis to thyroid storm. In the past, thyroid storm was commonly observed during thyroid surgery, especially in older children and adults, but improved preoperative management has markedly decreased the incidence of this complication. Today, thyroid storm occurs more commonly as a medical crisis rather than a surgical crisis.
Thyroid storm is a decompensated state of thyroid hormone–induced, severe hypermetabolism involving multiple systems and is the most extreme state of thyrotoxicosis. The clinical picture relates to severely exaggerated effects of THs due to increased release (with or without increased synthesis) or, rarely, increased intake of TH.
Heat intolerance and diaphoresis are common in simple thyrotoxicosis but manifest as hyperpyrexia in thyroid storm. Extremely high metabolism also increases oxygen and energy consumption. Cardiac findings of mild-to-moderate sinus tachycardia in thyrotoxicosis intensify to accelerated tachycardia, hypertension, high-output cardiac failure, and a propensity to develop cardiac arrhythmias. Similarly, irritability and restlessness in thyrotoxicosis progress to severe agitation, delirium, seizures, and coma. [1] GI manifestations of thyroid storm include diarrhea, vomiting, jaundice, and abdominal pain, in contrast to only mild elevations of transaminases and simple enhancement of intestinal transport in thyrotoxicosis.
Thyroid storm is precipitated by the following factors in individuals with thyrotoxicosis:
Thyroid storm can occur in children with thyrotoxicosis from any cause but is most commonly associated with Graves disease. Other reported causes of thyrotoxicosis associated with thyroid storm include the following:
Graves disease may also occur in children with Down syndrome or Turner syndrome and in association with other autoimmune conditions, including the following:
The pathophysiologic mechanisms of Graves disease are shown in the image below.
Although the exact pathogenesis of thyroid storm is not fully understood, the following theories have been proposed:
In the US, the true frequency of thyrotoxicosis and thyroid storm in children is unknown. The incidence of thyrotoxicosis increases with age. Thyrotoxicosis may affect as many as 2% of older women. Children constitute less than 5% of all thyrotoxicosis cases. Graves disease is the most common cause of childhood thyrotoxicosis and, in a possibly high estimate, reportedly affects 0.2-0.4% of the pediatric and adolescent population. About 1-2% of neonates born to mothers with Graves disease manifest thyrotoxicosis.
Based on nationwide surveys conducted between 2004 and 2008, the incidence of thyroid storm in Japan has been estimated to be 0.2 persons per 100,000 population, with the rate of thyroid storm in all thyrotoxic patients being 0.22%, and in hospitalized thyrotoxic patients, 5.4%. [7]
Thyrotoxicosis is 3-5 times more common in females than in males, especially among pubertal children. Thyroid storm affects a small percentage of patients with thyrotoxicosis. The incidence is presumed to be higher in females; however, no specific data regarding sex-specific incidence are available.
Neonatal thyrotoxicosis occurs in 1-2% of neonates born to mothers with Graves disease. Infants younger than 1 year constitute only 1% of cases of childhood thyrotoxicosis. More than two thirds of all cases of thyrotoxicosis occur in children aged 10-15 years. Overall, thyrotoxicosis occurs most commonly during the third and fourth decades of life. Because childhood thyrotoxicosis is more likely to occur in adolescents, thyroid storm is more common in this age group, although it can occur in patients of all ages.
Thyroid storm is an acute, life-threatening emergency. If untreated, thyroid storm is almost invariably fatal in adults (90% mortality rate) and is likely to cause a similarly severe outcome in children, although the condition is so rare in children that these data are not available. Death from thyroid storm may be a consequence of cardiac arrhythmia, congestive heart failure, hyperthermia, multiple organ failure or other factors [8] , though the precipitating factor is often the cause of death.
With adequate thyroid-suppressive therapy and sympathetic blockade, clinical improvement should occur within 24 hours. Adequate therapy should resolve the crisis within a week. Treatment for adults has reduced mortality to less than 20%. In one retrospective study from Japan of 1324 patients who were diagnosed with thyroid storm, the overall mortality was 10% [9] . In the same study, the following factors were associated with increased mortality risk in thyroid storm [9] :
In addition, a study by Swee et al of 28 patients with thyroid storm reported that CNS dysfunction of greater than mild severity appeared to be a risk factor for mortality. [10]
For excellent patient education resources, visit eMedicineHealth’s Thyroid and Metabolism Center. Also, see eMedicineHealth’s patient education articles Thyroid Problems and Thyroid Storm.
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Madhusmita Misra, MD, MPH Fritz Bradley Talbot and Nathan Bill Talbot Professor in Pediatrics, Harvard Medical School; Chief, Division of Pediatric Endocrinology, Massachusetts General Hospital
Madhusmita Misra, MD, MPH is a member of the following medical societies: American Pediatric Society, American Society for Bone and Mineral Research, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, Women in Endocrinology
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Novo Nordisk.
Abhay Singhal, MD, MS, MD
Abhay Singhal, MD, MS, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School
Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research
Disclosure: Nothing to disclose.
Robert P Hoffman, MD Professor and Program Director, Department of Pediatrics, Ohio State University College of Medicine; Pediatric Endocrinologist, Division of Pediatric, Endocrinology, Diabetes, and Metabolism, Nationwide Children’s Hospital
Robert P Hoffman, MD is a member of the following medical societies: American College of Pediatricians, American Diabetes Association, American Pediatric Society, Christian Medical and Dental Associations, Endocrine Society, Midwest Society for Pediatric Research, Pediatric Endocrine Society, Society for Pediatric Research
Disclosure: Nothing to disclose.
Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children’s Medical Center of New York; Professor of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research
Disclosure: Nothing to disclose.
Deborah E Campbell, MD, FAAP Professor of Pediatrics, Albert Einstein College of Medicine; Chief, Division of Neonatology, Children’s Hospital at Montefiore
Deborah E Campbell, MD, FAAP is a member of the following medical societies: Academic Pediatric Association, American Academy of Pediatrics, American Medical Association, American Pediatric Society, National Perinatal Association, New York Academy of Medicine
Disclosure: Nothing to disclose.
Thyroid Storm
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