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1.  Thyroid storm associated with Graves' disease covered by diabetic ketoacidosis: A case report 
Thyroid Research  2011;4:8.
Thyroid storm is a condition in which multiple organ dysfunction results from failure of the compensatory mechanisms of the body owing to excessive thyroid hormone activity induced by some factors in patients with thyrotoxicosis. While diabetic ketoacidosis (DKA) is an important trigger for thyroid storm, simultaneous development of DKA and thyroid storm is rare.
Case presentation
A 59-year-old woman with no history of either diabetes mellitus or thyroid disease presented to our hospital because of developing nausea, vomiting and diarrhea for 2 days. Physical examination showed mild disturbance of consciousness, fever, and tachycardia. There were no other signs of thyrotoxicosis. Laboratory studies revealed elevation of random blood glucose and glycosylated hemoglobin, strongly positive of urine acetone, and metabolic acidosis. Since DKA was diagnosed, we initiated the patient on treatment with administration of insulin and adequate fluid replacement. Although the hyperglycemia and acidosis were immediately relieved, the disturbance of consciousness and tachycardia remained persistent. Levels of FT3 and FT4 were extremely high and TSH was below the detectable limit. TRAb was positive. The thyroid storm score of Burch & Wartofsky was 75/140, and the thyroid storm diagnostic criteria of the Japan Thyroid Association were satisfied. Oral administration of thiamazole, potassium iodide and propranolol resulted in immediate relief of the tachycardia.
We encountered a case of thyroid storm associated with Graves' disease covered by DKA. Thyroid storm and DKA are both potentially fatal, and the prognosis varies depending on whether or not these conditions are detected and treated sufficiently early. The thyroid storm diagnostic criteria prepared in 2008 by the Japan Thyroid Association are very simple as compared to the Burch & Wartofsky scoring system for thyroid storm. The Japanese criteria may be useful in the diagnosis of this condition since they enable clinicians to identify a broad range of cases with thyroid storm. When dealing with cases of DKA or thyroid storm, it seems essential to bear in mind the possibility of the coexistence of these two diseases.
PMCID: PMC3094317  PMID: 21492449
2.  Respiratory Syncytial Virus Infection as a Precipitant of Thyroid Storm in a Previously Undiagnosed Case of Graves' Disease in a Prepubertal Girl 
Graves' disease is less common in prepubertal than pubertal children, and initial presentation with thyroid storm is rare. We report an 11-year-old prepubertal Hispanic girl who presented with a one-day history of respiratory distress, fever, and dysphagia. She had exophthalmos, a diffuse bilateral goiter and was agitated, tachycardic, and hypertensive. Nasal swab was positive for respiratory syncytial virus (RSV). She was diagnosed with thyroid storm and admitted to the pediatric intensive care unit. While infection is a known precipitant of thyroid storm and RSV is a common pediatric infection, to the best of our knowledge, this is the first reported case of RSV infection apparently precipitating thyroid storm in a prepubertal child.
PMCID: PMC3198741  PMID: 21603250
3.  H1N1 infection-induced thyroid storm 
Annals of Thoracic Medicine  2010;5(2):110-112.
A thyroid storm is a life-threatening exacerbation of thyrotoxicosis, and is usually characterized by hyperthermia, tachycardia, severe agitation and altered mental status. A thyroid storm may be triggered by many causes, including systemic pulmonary infections. Delay in prompt diagnosis leads to high mortality. We present the first case of H1N1 infection triggering a thyroid storm. The delay in diagnosis because of preoccupancy with the H1N1 pandemic may have contributed to the poor outcome. When assessing cases with H1N1 infection, physicians should be more vigilant in order not to miss other important diagnoses.
PMCID: PMC2883193  PMID: 20582177
Influenza A; H1N1; thyroid storm; infection induced thyroid dysfunction
4.  Thromboembolic complications of thyroid storm 
Thyroid storm is a rare but potentially life-threatening complication of hyperthyroidism. Early recognition and prompt treatment are essential. Atrial fibrillation can occur in up to 40% of patients with thyroid storm. Studies have shown that hyperthyroidism increases the risk of thromboembolic events. There is no consensus with regard to the initiation of anticoagulation for atrial fibrillation in severe thyrotoxicosis. Anticoagulation is not routinely initiated if the risk is low on a CHADS2 score; however, this should be considered in patients with thyroid storm or severe thyrotoxicosis with impending storm irrespective of the CHADS2 risk, as it appears to increase the risk of thromboembolic episodes. Herein, we describe a case of thyroid storm complicated by massive pulmonary embolism.
Learning points
Diagnosis of thyroid storm is based on clinical findings. Early recognition and prompt treatment could lead to a favourable outcome.Hypercoagulable state is a recognised complication of thyrotoxicosis.Atrial fibrillation is strongly associated with hyperthyroidism and thyroid storm.Anticoagulation should be considered for patients with severe thyrotoxicosis and atrial fibrillation irrespective of the CHADS2 score.Patients with severe thyrotoxicosis and clinical evidence of thrombosis should be immediately anticoagulated until hyperthyroidism is under control.
PMCID: PMC3965285  PMID: 24683480
5.  Thyroid Storm Complicated by Bicytopenia and Disseminated Intravascular Coagulation 
Patient: Male, 23
Final Diagnosis: Thyroid storm
Symptoms: Delirium • diarrhea • fever • hypertension • hyperventilation • tachycardia • weight loss
Medication: —
Clinical Procedure: —
Specialty: Endocrinology and Metabolic
Unusual clinical course
The clinical presentation of thyroid storm includes fever, tachycardia, hypertension, and neurological abnormalities. It is a serious condition with a high mortality rate. Furthermore, some other complications affect the clinical course of thyroid storm. Although it is reported that prognosis is poor when thyroid storm is complicated by disseminated intravascular coagulation syndrome (DIC) and leukopenia, reports of such cases are rare.
Case Report:
A 23-year-old man presented with delirium, high pyrexia, diarrhea, and weight loss of 18 kg over 2 months. According to the criteria of Burch and Wartofsky, he was diagnosed with thyroid storm on the basis of his symptom-complex and laboratory data that confirmed the presence of hyperthyroidism. Investigations also found leukopenia, thrombocytopenia, and disseminated intravascular coagulation, all of which are very rare complications of thyroid storm. We successfully treated him with combined therapy including anti-thyroid medication, despite leukopenia.
Early diagnosis and treatment are essential in ensuring a good outcome for patients with this rare combination of medical problems.
PMCID: PMC4121396  PMID: 25072662
Disseminated Intravascular Coagulation – complications; Hyperthyroidism; Thyroid Crisis
6.  Thyroid storm following radioactive iodine (RAI) therapy for pediatric graves disease 
Patient: Female, 11
Final Diagnosis: Thyroid storm
Symptoms: Diarrhea • tachycardia • tachypnea • tremor • wheezing
Medication: —
Clinical Procedure: —
Specialty: —
Rare disease
A growing number of pediatric endocrinologists treat Graves disease with radioactive iodine (RAI) therapy due to the typically definitive nature of I-131 therapy. Given the published benefits and perceived low risks of RAI when compared to surgery or long-term anti-thyroid medication, the trend towards therapy with RAI is likely to continue. Nevertheless, RAI is not without significant risk.
Case Report:
An 11-year-old girl with newly diagnosed Graves disease received RAI for definitive treatment of her hyperthyroidism. Within 24 hours of receiving I-131, she developed increasing sleepiness and eventually became unresponsive. Upon arrival at the emergency department she had a tonic-clonic seizure and was diagnosed with thyroid storm. Despite best efforts to manage her hyperthyroidism, she suffered a stroke of the left cerebral hemisphere that left her with persistent neurological deficits.
Although thyroid storm after thyroid ablation is rare, the significant morbidity and potential mortality of pediatric thyroid storm warrant further studies to determine if children with markedly elevated thyroid hormone concentrations at diagnosis should receive prolonged pretreatment with anti-thyroid drugs. While such an approach may reduce the efficacy of I-131 ablation, it can also reduce and hopefully eliminate the risk of post-ablative thyroid storm.
PMCID: PMC4026146  PMID: 24847412
Graves Disease; Hyperthyroidism; Thyroid Storm; Pediatrics; Iodine Radioisotopes
7.  Thyroid Storm—A Review of Cases at University of California, San Francisco 
California Medicine  1971;115(4):5-9.
Retrospective study of the diagnosis and management of the 8 cases of thyroid storm in a series of 400 hyperthyroid patients led to conclusion that thyroid storm is a clinical diagnosis based on a life-endangering illness in a hyperthyroid patient whose hyperthyroidism has been severely exacerbated by a serious precipitating illness, and that storm is manifest by the symptoms of hyperpyrexia, tachycardia and striking alterations in consciousness. No laboratory tests were diagnostic of storm, and the underlying precipitating cause of thyroid storm was the major determinant of survival. Vigorous therapy must include blocking synthesis of thyroid hormones with antithyroid drugs, blocking release of preformed hormone with iodine, meticulous attention to hydration and supportive therapy, as well as correction of precipitating cause of storm. The blocking of the sympathetic nervous system with reserpine or guanethidine or with alpha and beta blocking drugs may be exceedingly hazardous and requires skillful management and constant monitoring in a critically ill patient.
PMCID: PMC1517957  PMID: 5110595
8.  Animal Model of Respiratory Syncytial Virus: CD8+ T Cells Cause a Cytokine Storm That Is Chemically Tractable by Sphingosine-1-Phosphate 1 Receptor Agonist Therapy 
Journal of Virology  2014;88(11):6281-6293.
The cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory response driven by cytokine and immune cell components. The cytokine storm during influenza virus infection, whereby the amplified innate immune response is primarily responsible for pulmonary damage, has been well characterized. Now we describe a novel event where virus-specific T cells induce a cytokine storm. The paramyxovirus pneumonia virus of mice (PVM) is a model of human respiratory syncytial virus (hRSV). Unexpectedly, when C57BL/6 mice were infected with PVM, the innate inflammatory response was undetectable until day 5 postinfection, at which time CD8+ T cells infiltrated into the lung, initiating a cytokine storm by their production of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Administration of an immunomodulatory sphingosine-1-phosphate (S1P) receptor 1 (S1P1R) agonist significantly inhibited PVM-elicited cytokine storm by blunting the PVM-specific CD8+ T cell response, resulting in diminished pulmonary disease and enhanced survival.
IMPORTANCE A dysregulated overly exuberant immune response, termed a “cytokine storm,” accompanies virus-induced acute respiratory diseases (VARV), is primarily responsible for the accompanying high morbidity and mortality, and can be controlled therapeutically in influenza virus infection of mice and ferrets by administration of sphingosine-1-phosphate 1 receptor (S1P1R) agonists. Here, two novel findings are recorded. First, in contrast to influenza infection, where the cytokine storm is initiated early by the innate immune system, for pneumonia virus of mice (PVM), a model of RSV, the cytokine storm is initiated late in infection by the adaptive immune response: specifically, by virus-specific CD8 T cells via their release of IFN-γ and TNF-α. Blockading these cytokines with neutralizing antibodies blunts the cytokine storm and protects the host. Second, PVM infection is controlled by administration of an S1P1R agonist.
PMCID: PMC4093868  PMID: 24672024
9.  Cholestatic hepatic injury due to a thyroid storm: a case report from a resource limited setting 
Thyroid Research  2012;5:6.
Thyroid storm is an endocrinological emergency caused by an exacerbation of the hyperthyroid state and is characterized by multi organ dysfunction. Liver dysfunction or injury predominantly of a cholestatic type is one of the atypical manifestations of thyroid storm and has been previously described in literature. However, there have been few published case reports among African patients and from resource limited settings.
Case report
We report a case of a 21 year old Ugandan female patient who presented with a thyroid storm due to untreated Graves’ disease complicated by cholestatic hepatic injury, congestive heart failure and acute kidney injury.
This case highlights the varied multi organ dysfunctions seen in a patient with thyroid storm with emphasis on liver injury mainly to increase awareness among clinicians in resource limited settings. Mechanisms of liver injury due to thyroid storm or hyperthyroidism are discussed in the literature review.
PMCID: PMC3475043  PMID: 22839423
Thyroid storm; Cholestatic hepatic injury; Cholestasis
10.  A patient who experienced thyroid storm complicated by rhabdomyolysis, deep vein thrombosis, and a silent pulmonary embolism: a case report 
BMC Research Notes  2013;6:198.
Thyroid storm is a serious condition of thyrotoxicosis. Hyperthyroidism often presents with thrombotic events, especially at cerebral sites; however, the possible association between a lower extremity deep vein thrombosis (LEDVT) and thyroid storm has not been previously reported. We encountered a patient who developed thyroid storm, associated with rhabdomyolysis, followed by LEDVT and a small silent pulmonary embolism (PE). The case is discussed with references to the pertinent literature.
Case presentation
A 50-year-old woman with no past medical history was referred to our hospital because of severe diarrhea, muscle weakness in her lower limbs (manual muscle testing: MMT 3), and disturbances of consciousness. She was diagnosed as having Graves’ disease based on the presence of struma, exophthalmos, and hyperthyroidism with TSH receptor antibody positivity; we further determined that the patient was experiencing thyroid storm based on the results of the Burch-Wartofsky scoring system and a Japanese diagnostic criteria. Treatment with steroids, iodine potassium, methimazole, and propranolol was initiated. Severe watery diarrhea continued, and the laboratory data revealed hypokalemia (2.0 meq/L). On day 14, a blood analysis showed a sudden elevation in her creatinine kinase (CK) level, leading to a diagnosis of rhabdomyolysis. Thereafter, the muscle weakness in her lower limbs advanced to a degree of MMT 1. Seven days after the diagnosis of rhabdomyolysis, pitting edema began to appear in bilateral lower extremities. Contrast-enhanced CT scans revealed a LEDVT involving the left common iliac vein, bilateral femoral veins, and left popliteal vein. Furthermore, a small PE was identified. Hyperthyroidism often presents with thrombotic events, especially at cerebral sites, but few reports of PE or LEDVT have been made.
This case suggests that the occurrence of thyroid storm may be associated with a risk of LEDVT and/or PE. We suggest that DVT preventive measures are undertaken, and that a lower limb venous echo or contrast-enhanced CT examination would be considered if LEDVT is suspected.
PMCID: PMC3669617  PMID: 23687997
11.  Thyroid storm in a young woman resulting in bilateral basal ganglia infarction. 
Postgraduate Medical Journal  1993;69(816):813-815.
We describe a 30 year old woman who presented with thyroid storm. She had non-specific symptoms and few clinical signs of hyperthyroidism despite markedly raised thyroid hormone concentrations. Soon after admission her behaviour became abnormal and her level of consciousness deteriorated. Despite the rapid restoration of thyroid hormone concentrations to normal using conventional therapies, and correction of hypoxia resulting from acute pulmonary oedema, her level of consciousness did not improve. Cranial CT scanning revealed extensive bilateral basal ganglia infarction, a previously unreported complication of thyroid storm. This observation suggests that thyroid storm may predispose to hypoxic neurological damage.
PMCID: PMC2399964  PMID: 8290416
12.  Into the Eye of the Cytokine Storm 
Summary: The cytokine storm has captured the attention of the public and the scientific community alike, and while the general notion of an excessive or uncontrolled release of proinflammatory cytokines is well known, the concept of a cytokine storm and the biological consequences of cytokine overproduction are not clearly defined. Cytokine storms are associated with a wide variety of infectious and noninfectious diseases. The term was popularized largely in the context of avian H5N1 influenza virus infection, bringing the term into popular media. In this review, we focus on the cytokine storm in the context of virus infection, and we highlight how high-throughput genomic methods are revealing the importance of the kinetics of cytokine gene expression and the remarkable degree of redundancy and overlap in cytokine signaling. We also address evidence for and against the role of the cytokine storm in the pathology of clinical and infectious disease and discuss why it has been so difficult to use knowledge of the cytokine storm and immunomodulatory therapies to improve the clinical outcomes for patients with severe acute infections.
PMCID: PMC3294426  PMID: 22390970
13.  Thyroid Storm Masked by Hemodialysis and Glucocorticoid Therapy in a Patient with Rheumatoid Arthritis 
Thyroid function test values are generally at low levels in patients with end-stage kidney disease. Life-threatening thyrotoxicosis or thyroid storm is rare, especially in hemodialysis (HD) patients, and is characterized by multisystem involvement and a high mortality rate if not immediately recognized and treated. Here, we report a female patient with severe symptomatic thyroid storm, receiving long-term HD and glucocorticoid therapy. Methimazole at a dose of 15 mg per day, β-adrenergic blockade and HD succeeded in controlling the patient's condition by gradually adjusting the target dry weight for hyperthyroidism-induced weight loss. When she was discharged from the hospital, her dry weight was reduced from 47.2 to 39.2 kg. The management of patients with severe symptomatic thyroid storm on HD represents a rare scenario. It is essential to initiate the available treatments as early as possible to reduce its mortality.
PMCID: PMC3482076  PMID: 23197948
Thyroid storm; Graves’ disease; Hemodialysis; Glucocorticoid therapy
14.  Persistent perioperative tachycardia and hypertension diagnosed as thyroid storm induced by a hydatidiform mole: a case report 
Korean Journal of Anesthesiology  2014;67(3):205-208.
Thyroid storm is a critical complication of molar pregnancy. However, early diagnosis of it is difficult because it is a rare complication and usually presents nonspecific findings. In this case report, we present a woman with molar pregnancy who had persistent tachycardia and hypertension. She was diagnosed initially with preeclampsia and sepsis as complications of molar pregnancy. During dilation and curettage under general anesthesia with sevoflurane and remifentanil, tachycardia and hypertension remained even with continuous infusion of labetalol. The patient was subsequently diagnosed with thyroid storm associated with molar pregnancy. She was restored to a clinically euthyroid state 1 day after the operation, and her thyroid function test and β-hCG values were normal 3 months later. The anesthesiologists should bear in mind the possibility of thyroid storm in patients with molar pregnancies who show persistent tachycardia and hypertension.
PMCID: PMC4188767  PMID: 25302097
Hydatidiform mole; Thyroid crisis
15.  Thyroid Storm Caused by a Chinese Herb Contaminated with Thyroid Hormones 
Patient: Male, 70
Final Diagnosis: Thyroid storm
Symptoms: Atrial fibrillation • confusion • hyperthermia • tachycardia
Medication: —
Clinical Procedure: Intubation • cardioversion
Specialty: Critical Care Medicine
Adverse events of drug therapy
We report a case of thyroid storm caused by consuming a Chinese herb contaminated with thyroid hormones.
Case Report:
A 70-year-old man presented to an emergency department after 2 days of nausea, vomiting, and weakness. Three days previously, he had started taking Cordyceps powder and “Flower Man Sang Hung” as recommended by his Chinese physician. Following admission, the patient deteriorated and was eventually diagnosed with thyroid storm complicated by rapid atrial fibrillation requiring cardioversion, intubation, and intensive care admission. The analysis of the Chinese herb “Flower Man Sang Hung” was positive for levothyroxine. The patient was extubated 11 days after admission and discharged to a rehabilitation centre after 17 days of hospitalization. The Chinese medicine physician was informed of the events.
Herbal products can be the source of illness, medication interactions, and contamination. Awareness should be raised among Chinese medicine physicians, allopathic physicians, and their patients. Clinicians should also have a low threshold of suspicion to seek laboratory analysis of suspect substances when the cause of the clinical presentation is unclear.
PMCID: PMC4321408  PMID: 25644333
Herb-Drug Interactions; Thyroid Hormones; Thyrotoxicosis
16.  Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease 
Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection.
Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of São Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles.
Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease.
The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis.
Author Summary
The pathogenesis of severe dengue virus (DENV) infection is still not fully understood. It is hypothesized that it is caused by a cytokine storm as is described in severe sepsis. In the sepsis field, the potent immunostimulator lipopolysaccharide (LPS) is proposed to play an important role in the development of a cytokine storm. In a previous study we have found elevated levels of LPS in children with severe DENV infection. In this study we have investigated if we could confirm that microbial translocation occurs in DENV-infected patients. Moreover, we have determined the levels of thirty cytokines to get more insight in the cytokine storm during DENV infections and we have investigated whether microbial translocation is associated with immune activation. The patients in this cohort were classified according to their clinical presentation. Furthermore, a cluster analysis based on the expression of the determined cytokines was applied to identify patients with similar cytokine profiles. With these two techniques, we identified cytokines that may contribute significantly to the cytokine storm, and we could relate elevated levels of LPS to patients with a pro-inflammatory cytokine profile.
PMCID: PMC3662706  PMID: 23717702
17.  Clinical Concepts on Thyroid Emergencies 
Objective: Thyroid-related emergencies are caused by overt dysfunction of the gland which are so severe that require admission to intensive care units (ICU) frequently. Nonetheless, in the ICU setting, it is crucial to differentiate patients with non-thyroidal illness and alterations in thyroid function tests from those with intrinsic thyroid disease. This review presents and discusses the main etiopathogenetical and clinical aspects of hypothyroid coma (HC) and thyrotoxic storm (TS), including therapeutic strategy flow-charts. Furthermore, a special chapter is dedicated to the approach to massive goiter, which represents a surgical thyroid emergency.
Data Source: We searched the electronic MEDLINE database on September 2013.
Data Selection and Data Extraction: Reviews, original articles, and case reports on “myxedematous coma,” “HC,” “thyroid storm,” “TS,” “massive goiter,” “huge goiter,” “prevalence,” “etiology,” “diagnosis,” “therapy,” and “prognosis” were selected.
Data Synthesis and Conclusion: Severe excess or defect of thyroid hormone is rare conditions, which jeopardize the life of patients in most cases. Both HC and TS are triggered by precipitating factors, which occur in patients with severe hypothyroidism or thyrotoxicosis, respectively. The pillars of HC therapy are high-dose l-thyroxine and/or tri-iodothyroinine; i.v. glucocorticoids; treatment of hydro-electrolyte imbalance (mainly, hyponatraemia); treatment of hypothermia; often, endotracheal intubation and assisted mechanic ventilation are needed. Therapy of TS is based on beta-blockers, thyrostatics, and i.v. glucocorticoids; eventually, high-dose of iodide compounds or lithium carbonate may be of benefit. Surgery represents the gold standard treatment in patients with euthyroid massive nodular goiter, although new techniques – e.g., percutaneous laser ablation – are helpful in subjects at high surgical risk or refusing operation.
PMCID: PMC4076793  PMID: 25071718
hypothyroid coma; thyrotoxic storm; hyperthyroidism; thyrotoxicosis; hypothyroidism; massive goiter
18.  Acute Thyrotoxic Bulbar Myopathy with Encephalopathic Behaviour: An Uncommon Complication of Hyperthyroidism 
Case Reports in Endocrinology  2013;2013:369807.
Objective. Acute thyrotoxic bulbar palsy is rare, severe, and rapidly progressive. We describe a case of thyrotoxicosis with bulbar palsy, encephalopathy, and pyramidal tract dysfunction. Case Report. 64-year-old white male with toxic multinodular goiter presented with rapid atrial fibrillation. He had mild tremor, normal cranial nerve examination, 4/5 strength in all extremities, normal reflexes, and down going plantars. TSH was low at 0.09 (normal: 0.34–5.6 uIU/mL), and free T4 was high at 5.22 (normal: 0.47–1.41 ng/dL). Despite optimal AV nodal blockade, he had persistent rapid atrial fibrillation. He later developed cervical dystonia, rigidity, clonus, dysarthria, dysphagia, vocal cord palsy, and absent gag reflex. Thyroid storm was suspected. Neuroimaging and cerebrospinal fluid cultures were nondiagnostic. Acetylcholine receptor antibodies were negative. Swallow ability was impaired with heavy secretions. Remarkable improvement in symptoms was noted after initiation of treatment for thyroid storm. Conclusion. Pyramidal tract symptoms and bulbar palsy may occur with thyrotoxicosis. Cranial nerve involvement and encephalopathy raise a question of primary brain mechanism causing bulbar palsy. This is reversible with prompt treatment of thyroid storm.
PMCID: PMC3690644  PMID: 23840978
19.  Surgical Management of an Atypical Presentation of a Thyroid Storm 
Thyroid storm is a rare complication of Graves' disease that can carry a poor prognosis. In order to prevent major complications, thyroid storm must be quickly identified in patients and treatment must be promptly implemented. Medical treatment is usually initiated with antithyroid medications, such as propylthiouracil (PTU), methimazole, and beta-blockers. However, some patients may experience adverse reactions to these medications and alternate treatment options must be explored.
Case Presentation:
We report a case of a 30-year-old female initiated on PTU after diagnosis with Graves' disease that later presented an acute thyroid storm.
Therapy was changed to methimazole, yet the patient subsequently developed angioedema and dyspnea. Medical management was discontinued and emergent thyroidectomy was performed without complication.
PMCID: PMC3997950  PMID: 24782903
Thyroid Crisis; Thyroidectomy; Graves' Disease; Antithyroid Agents
20.  Fetal death due to upper airway compromise complicated by thyroid storm in a mother with uncontrolled Graves' disease: a case report 
We report an unusual case of upper airway compromise complicated by thyroid storm in a pregnant woman with Graves' disease, ending with the in utero death of the fetus. This complication might have developed due to upper airway edema as a result of poorly controlled hyperthyroidism.
Case presentation
A 41-year-old Turkish woman at 27 weeks' gestation suffering from Graves' disease was referred to our emergency department with a diagnosis of respiratory arrest. She was unconscious and had been intubated. Her laboratory results were compatible with thyrotoxicosis. The patient had suffered from respiratory difficulty for a long time and had stopped using her antithyroid medications after the first trimester of pregnancy. One day before, she had visited an obstetrician because her respiratory distress had increased. At that time, her fetus was still alive. She was given oxygen therapy and then sent home. With a presumptive diagnosis of thyroid storm, she was admitted to the intensive care unit and treated with aggressive medical therapy. The baby was found to be no longer alive and was delivered vaginally after labor induction. The mother was discharged 10 days later with maintenance therapy.
Hyperthyroidism during pregnancy warrants very close attention and should almost always be treated with appropriate antithyroid medications. Maternal respiratory distress in such patients can be an early sign of impending upper airway compromise and thyroid storm, which can endanger the mother and fetus unless prompt and aggressive therapy is initiated.
PMCID: PMC2726526  PMID: 19830171
21.  Thyroid storm induced by trauma due to spear fishing‐gun trident impaction in the neck 
Emergency Medicine Journal : EMJ  2007;24(5):355-356.
A rare case of thyroid storm induced by thyroid gland injury because of penetrating neck trauma is reported. The injury was because of a spear fishing‐gun trident impaction in the neck. The diagnosis of thyroid gland injury was suspected by preoperative clinical examination and established during neck exploration in the theatre. The gland injury led to thyroid storm owing to the rupture of acini and liberation of T4 into the bloodstream. Withdrawal of the impacted trident along with subtotal thyroid lobectomy and repair of soft tissue damage in addition to supported treatments, which corrected the hyperthyroid state, led to uneventful recovery.
PMCID: PMC2658486  PMID: 17452705
22.  Τhyroid storm induced by trauma due to spear-fishing gun trident impaction in the neck 
BMJ Case Reports  2009;2009:bcr12.2008.1391.
A rare case of thyroid storm induced by thyroid gland injury because of penetrating neck trauma is reported. The injury was the result of a spear-fishing gun trident impaction in the neck. The diagnosis of thyroid gland injury was suspected by preoperative clinical examination and established during neck exploration in the theatre. The gland injury led to thyroid storm owing to the rupture of acini and liberation of thyroxine (T4) into the bloodstream. Withdrawal of the impacted trident along with subtotal thyroid lobectomy and repair of soft tissue damage in addition to supported treatments, which corrected the hyperthyroid state, led to uneventful recovery.
PMCID: PMC3027748  PMID: 21709842
23.  When it Rains it Pours: Real-time Situational Awareness for Two Weather Emergencies in Connecticut 
To characterize the utility of the Connecticut Hospital Emergency Department Syndromic Surveillance (HEDSS) system for real-time situational awareness during two weather-related emergencies.
On August 28, 2011 Tropical Storm Irene made landfall in Connecticut. On October 29, 2011 Connecticut was impacted by Winter Storm Alfred. Both of these storms included high winds and heavy precipitation which resulted in prolonged power outages, disruption of public drinking water systems, property damage, and widespread debris throughout the state. The HEDSS System was utilized to provide real-time situational awareness during the response and recovery phases of both storm events.
The HEDSS System receives electronic patient abstract data from 21 of 32 emergency departments on a daily basis. Free-text chief complaint data are characterized into syndrome categories. ED visits for carbon monoxide exposure (CO), gastrointestinal illness (GI), injury, hypothermia, motor vehicle accidents (MVA), and asthma syndromes were monitored throughout the response and recovery periods of both storm. Odds Ratios were calculated using the two weeks pre-and post-storm as reference dates. CO visits were further assessed for geographic and demographic trends to target public health messages. The HEDSS system was evaluated to make recommendations for event monitoring during future public health emergencies.
Following both storms there was a high completeness of daily HEDSS reporting despite extensive power outages (96% post-tropical storm, 91% post-winter storm). Increased emergency department utilization for CO (OR: 26.20, 95% CI: 3.57–192.64) was observed post-tropical storm. Increased emergency department utilization for CO (OR: 14.61, 95% CI: 7.43–28.72), hypothermia (OR: 17.02, 95% CI: 3.01–359.30), and asthma (OR: 1.17, 95% CI: 1.05–1.30) were observed following the winter storm. Regional increases in ED utilization for injuries and MVA were observed following both storm events; no increase in GI was associated with either storm event.
During the 2 weeks post-tropical storm 28 cases of CO exposure were reported through HEDSS and 5 cases through laboratory surveillance; during the winter storm 131 cases were reported through HEDSS and 162 through reportable disease surveillance. Of the 167 cases reported through laboratory surveillance, 111 (66%) were from hospitals that sent data to HEDSS hospitals and 94(56%) were able to be matched to a specific ED record; of these 22(20%) were characterized as visiting the ED for CO syndrome, 13(14%) had symptoms consistent with CO as their chief complaint, 11(12%) had smoke/gasoline inhalation exposures as their chief complaint and 2(2%) had unrelated chief complaints. During the post-storm period the HEDSS systems detected 137 potential CO exposures that were not reported through laboratory surveillance.
Tropical Storm Irene and Winter Storm Alfred both had significant health impacts, particularly increased ED utilization for CO due to prolonged power outages. The HEDSS system is the only all-hazards surveillance system that was able to provide near-real time information during the storm response phase. In addition to the current CO syndrome definition, where the chief complaint must specifically mention the term CO, a broader definition should also be used in the future to better assess the magnitude of CO-related exposures. The broad definition should include symptomology and related exposures, such as smoke inhalation, to improve case detection. The HEDSS system should continue to be used in conjunction with reportable disease surveillance for situational monitoring during public health emergencies.
PMCID: PMC3692947
emergency department; public health practice; syndromic surveillance; carbon monoxide; weather
24.  IL-33/ST2 Correlates with Severity of Haemorrhagic Fever with Renal Syndrome and Regulates the Inflammatory Response in Hantaan Virus-Infected Endothelial Cells 
PLoS Neglected Tropical Diseases  2015;9(2):e0003514.
Hantaan virus (HTNV) causes a severe lethal haemorrhagic fever with renal syndrome (HFRS) in humans. Despite a limited understanding of the pathogenesis of HFRS, the importance of the abundant production of pro-inflammatory cytokines has been widely recognized. Interleukin 33 (IL-33) has been demonstrated to play an important role in physiological and pathological immune responses. After binding to its receptor ST2L, IL-33 stimulates the Th2-type immune response and promotes cytokine production. Depending on the disease model, IL-33 either protects against infection or exacerbates inflammatory disease, but it is unknown how the IL-33/ST2 axis regulates the immune response during HTNV infection.
Methodology/Principal Findings
Blood samples were collected from 23 hospitalized patients and 28 healthy controls. The levels of IL-33 and soluble ST2 (sST2) in plasma were quantified by ELISA, and the relationship between IL-33, sST2 and the disease severity was analyzed. The role of IL-33/sST2 axis in the production of pro-inflammatory cytokines was studied on HTNV-infected endothelial cells. The results showed that the plasma IL-33 and sST2 were significantly higher in patients than in healthy controls. Spearman analysis showed that elevated IL-33 and sST2 levels were positively correlated with white blood cell count and viral load, while negatively correlated with platelet count. Furthermore, we found that IL-33 enhanced the production of pro-inflammatory cytokines in HTNV-infected endothelial cells through NF-κB pathway and that this process was inhibited by the recombinant sST2.
Our results indicate that the IL-33 acts as an initiator of the “cytokine storm” during HTNV infection, while sST2 can inhibit this process. Our findings could provide a promising immunotherapeutic target for the disease control.
Author Summary
Hantaan virus (HTNV) causes human hemorrhagic fever with renal syndrome (HFRS) with a mortality rate of approximately 15% in Asia. At present, the primary treatment for HFRS is limited to critical care management and the use of anti-viral drugs, such as Ribavirin. However, the cytokine storm at the acute phase of HFRS, which is thought to contribute to the development of the disease, is still lacking an effective way to prevent. An alternative way to prevent the development of cytokine storm is of priority to overcome the problem. We found that IL-33 and sST2 levels were higher in the plasma of HFRS patients, especially in their acute phase. Although both of them were positively correlated with the severity of the diseases, they acted in different roles in the regulation of the immune response during HTNV infection. In vitro study showed that IL-33 acted as an initiator of the cytokine storm in HTNV-infected endothelial cells, while sST2 acted as an inhibitor of the process. For the first time, we defined the IL-33/ST2 axis as inflammatory regulators during HTNV infection. Our results may provide a novel therapeutic target of HTNV infections.
PMCID: PMC4319827  PMID: 25658420
25.  A patient with Graves' disease who survived despite developing thyroid storm and lactic acidosis 
Upsala Journal of Medical Sciences  2010;115(4):282-286.
A 56-year-old woman with Graves' disease presented with the complaints of diarrhea and palpitations. Physical examination and laboratory data revealed hypothermia and signs of mild hyperthyroidism, heart failure, hepatic dysfunction with jaundice, hypoglycemia, and lactic acidosis. The patient was diagnosed as having developed the complication of thyroid storm in the absence of marked elevation of the thyroid hormone levels, because of the potential hepatic and cardiac dysfunctions caused by heavy alcohol drinking. A year later, after successful treatment, the patient remains well without any clinical evidence of heart failure or hepatic dysfunction. Thyroid storm associated with lactic acidosis and hypothermia is a serious condition and has rarely been reported. Prompt treatment is essential even if the serum thyroid hormone levels are not markedly elevated. We present a report about this patient, as her life could eventually be saved.
PMCID: PMC2971487  PMID: 20731531
Graves' disease; hypoglycemia; lactic acidosis; thyroid storm

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