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.
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.
Influenza A; H1N1; thyroid storm; infection induced thyroid dysfunction
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.
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.
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.
Thyroid storm; Cholestatic hepatic injury; Cholestasis
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.
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.
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.
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.
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.
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.
Thyroid storm; Graves’ disease; Hemodialysis; Glucocorticoid therapy
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.
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.
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.
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.
Graves' disease; hypoglycemia; lactic acidosis; thyroid storm
Hurricanes Katrina and Rita caused widespread damage that resulted in increased stress levels for families living in the New Orleans area. This study examined the relationship between this stress and the onset of puberty in children by conducting a retrospective chart review of patients referred before and after the storm to a pediatric endocrine practice in New Orleans. The total number of new patients referred and the incidence of diagnoses that are unlikely to be affected by stress (ie, thyroid disease and premature adrenarche) were essentially unchanged. On the other hand, the incidence of central precocious puberty decreased by 52% after the storm, while the incidence of pubertal delay increased by 9% in the post storm period. This study thus provides evidence that stress delays the onset of puberty in children.
Hurricane Katrina; puberty; stress
An unusual encounter of a thyroid storm, on two separate occasions, is reported in a patient with metastatic differentiated thyroid cancer following initially direct trauma to, and later tumour embolisation of, a metastatic skeletal lesion. Shortly after a fall, our patient presented with pain and swelling in the right shoulder, high fever, change in mental status, anorexia, nausea and vomiting, tachycardia and dehydration. The laboratory tests were consistent with hyperthyroidism. As the patient improved, arterial embolisation of the large right humerus metastasis was performed to decrease the tumour burden. The patient, however, developed a similar clinical and biochemical picture to that at her presentation, with a very high free thyroxine (T4) level, a few days after successful embolisation. Treatment of the thyroid storm was initiated and the patient eventually improved. Awareness of such occurrences is helpful in early diagnosis and effective management of this potentially fatal complication.
Thyroid storm is a known complication of thyroid surgery. Nowadays, it is commonly seen in thyrotoxic patients. In this case report we discuss a patient who presented with acute abdomen and normothermia and was discovered to have thyrotoxicosis, a rare feature of thyroid storm.
Thyroid storm; acute abdomen
The cytokine storm is an aggressive immune response characterized by the recruitment of inflammatory leukocytes and exaggerated levels of cytokines and chemokines at the site of infection. Here we review evidence that cytokine storm directly contributes to the morbidity and mortality resulting from influenza virus infection and that sphingosine-1-phosphate (S1P) receptor agonists can abort cytokine storms providing significant protection against pathogenic human influenza viral infections. In experiments using murine models and the human pathogenic 2009 influenza viruses, S1P1 receptor agonist alone reduced deaths from influenza virus by over 80% as compared to lesser protection (50%) offered by the antiviral neuraminidase inhibitor oseltamivir. Optimal protection of 96% was achieved by combined therapy with the S1P1 receptor agonist and oseltamivir. The functional mechanism of S1P receptor agonist(s) action and the predominant role played by pulmonary endothelial cells as amplifiers of cytokine storm during influenza infection are described.
cytokine storm; influenza; pulmonary endothelial cells; sphingosine-1-phosphate (S1P) receptor (rec) signaling; S1P receptor agonist therapy
Cytokine storm during viral infection is a prospective predictor of morbidity and mortality, yet the cellular sources remain undefined. Here, using genetic and chemical tools to probe functions of the S1P1 receptor, we elucidate cellular and signaling mechanisms important in initiating cytokine storm. While S1P1 receptor is expressed on endothelial cells and lymphocytes within lung tissue, S1P1 agonism suppresses cytokines and innate immune cell recruitment in wild-type and lymphocyte deficient mice, identifying endothelial cells as central regulators of cytokine storm. Furthermore, our data reveal immune cell infiltration and cytokine production as distinct events both orchestrated by endothelial cells. Moreover, we demonstrate that suppression of early innate immune responses through S1P1 signaling results in reduced mortality during infection with a human pathogenic strain of influenza virus. Modulation of endothelium with a specific agonist suggests that diseases where amplification of cytokine storm is a significant pathological component could be chemically tractable.
Thyroidectomy is the most common endocrine surgical procedure being carried out throughout the world. Besides, many patients who have deranged thyroid physiology, namely hyperthyroidism and hypothyroidism, have to undergo various elective and emergency surgical procedures at some stage of their life. The attending anesthesiologist has to face numerous daunting tasks while administering anesthesia to such patients. The challenging scenarios can be encountered at any stage, be it preoperative, intra-op or postoperative period. Preoperatively, deranged thyroid physiology warrants optimal preparation, while anticipated difficult airway due to enlarged thyroid gland further adds to the anesthetic challenges. Cardiac complications are equally challenging as also the presence of various co-morbidities which make the task of anesthesiologist extremely difficult. Thyroid storm can occur during intra-op and post-op period in inadequately prepared surgical patients. Postoperatively, numerous complications can develop that include hemorrhage, laryngeal edema, nerve palsies, tracheomalacia, hypocalcemic tetany, pneumothorax, etc., The present review aims at an in-depth analysis of potential risk factors and challenges during administration of anesthesia and possible complications in patients with thyroid disease.
Airway management; carbimazole; propanolol; thyroid; thyroidectomy; thyroxin; tracheomalacia
Thyrotoxicosis is a common endocrine condition that may be secondary to a number of underlying processes. Thyroid storm (also known as thyroid or thyrotoxic crisis) represents the severe end of the spectrum of thyrotoxicosis and is characterized by compromised organ function. Whilst rare in the modern era, the mortality rate remains high, and prompt consideration of this endocrine emergency, with specific treatments, can improve outcomes.
hyperthyroidism; thyroid storm; thyrotoxic crisis; thyrotoxicosis
This study was carried out to evaluate the clinical presentation, surgical treatment, complications, and risk of malignancy for large substernal goiter. From March 2010 to December 2012, 12 patients with large substernal thyroid goiter who underwent surgery in our Department were enrolled in the study. Their medical records were retrospectively analyzed. Collar-shaped incision was adequate for resection of the lesions in 10 (83%) patients, while two (17%) patients required combined cervical-thoracic incision. In addition, one case was subjected to postoperative tracheotomy. Transient hypocalcaemia occurred in one case. The incidence of transient hoarseness, tracheomalacia and hypothyroidism was 8.3%. There was no perioperative bleeding, thyroid storm as well as other serious complications. All patients were clinically cured. Therefore, cervical collar incision is nearly always adequate for most cases of larger substernal goiter, and sternotomy can be avoided. Furthermore, the application of intraoperative ultrasonic knife can effectively reduce intraoperative and postoperative complications. Aggressive perioperative management is crucial for the successful removal of large substernal goiter.
Substernal goiter; operative approach; ultrasonic knife; complications
Hypothalamic neurosecretory systems are fundamental regulatory circuits influenced by thyroid hormone. Monocarboxylate-transporter-8 (MCT8)-mediated uptake of thyroid hormone followed by type 3 deiodinase (D3)-catalyzed inactivation represent limiting regulatory factors of neuronal T3 availability. In the present study we addressed the localization and subcellular distribution of D3 and MCT8 in neurosecretory neurons and addressed D3 function in their axons. Intense D3-immunoreactivity was observed in axon varicosities in the external zone of the rat median eminence and the neurohaemal zone of the human infundibulum containing axon terminals of hypophysiotropic parvocellular neurons. Immuno-electronmicroscopy localized D3 to dense-core vesicles in hypophysiotropic axon varicosities. N-STORM-superresolution-microscopy detected the active center containing C-terminus of D3 at the outer surface of these organelles. Double-labeling immunofluorescent confocal microscopy revealed that D3 is present in the majority of GnRH, CRH and GHRH axons but only in a minority of TRH axons, while absent from somatostatin-containing neurons. Bimolecular-Fluorescence-Complementation identified D3 homodimers, a prerequisite for D3 activity, in processes of GT1-7 cells. Furthermore, T3-inducible D3 catalytic activity was detected in the rat median eminence. Triple-labeling immunofluorescence and immuno-electronmicroscopy revealed the presence of MCT8 on the surface of the vast majority of all types of hypophysiotropic terminals. The presence of MCT8 was also demonstrated on the axon terminals in the neurohaemal zone of the human infundibulum. The unexpected role of hypophysiotropic axons in fine-tuned regulation of T3 availability in these cells via MCT8-mediated transport and D3-catalyzed inactivation may represent a novel regulatory core mechanism for metabolism, growth, stress and reproduction in rodents and humans.
Kivalina is a northwest Alaska barrier island village of 400 people vulnerable to storm surges exacerbated recently by delayed winter sea and shore ice formation. The village has no in-home piped water or sewage; the “washeteria” is the only structure providing public showers, laundry facilities and flush toilets. In October 2004, a storm damaged the washeteria septic system resulting in prolonged facility closures. We assessed rates of gastrointestinal, respiratory and skin infections potentially impacted by prolonged washeteria closures.
We obtained washeteria closure dates from 2003 to July 2009 and defined >7 day closure as prolonged. We received de-identified data on all Kivalina clinic visits from 2003 to 2009 and selected visits with ICD-9 diagnosis codes for respiratory, skin, or gastrointestinal infection; subsequent same patient/same illness-category visits within 14 days were excluded. We compared annual visit rates, for all ages combined, before (2003–2004) and after (2005–2009) the “2004” storm.
The washeteria had prolonged closures for 34 days (4.7%) in the 2 years 2003–2004 and 864 days (51.7%) between January 2005 and July 2009. Closures ranged from 8 to 248 days. Respiratory infection rates declined significantly from 1.32 visits/person/year in the 2003–2004 period to 0.99 visits/person/year in the 2005–2009 period. There was a significant increase in skin infection rates after 2004, peaking at 0.28 visits/person/year in 2007 and then declining significantly to 0.15 visits/person/year in 2009. Gastrointestinal infection rates remained stable and low throughout (average: 0.05 visits/person/year). No temporal association was observed between respiratory, gastrointestinal or skin infection rates and prolonged washeteria closures.
The Kivalina washeteria was closed frequently and for extended periods between 2005 and 2009. Initial closures possibly resulted in increased skin infection rates. No increase in respiratory or gastrointestinal infections was noted. Evaluation of community adaptations to closures and other factors (e.g. childhood pneumococcal vaccination) would expand understanding of these findings.
infectious diseases; water; water access
Inflammation is the body's first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis, do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response.
Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes.
Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.
Objective: To summarize the experience in the peri-operative treatment of giant nodular goiter.
Methods: A total of 123 patients with giant nodular goiter sized 6~20 cm were admitted into our hospital from 1990 to 2011 and the clinical data were retrospectively analyzed. These patients underwent total or subtotal thyroidectomy.
Results: All patients underwent surgical intervention. Unilateral subtotal thyroidectomy was performed in 40 patients, unilateral total thyroidectomy in 1 patient, bilateral subtotal thyroidectomy in 79 patients, and unilateral total thyroidectomy, removal of entire isthmus and contralateral subtotal thyroidectomy in 3 patients. Nodular goiter was pathologically proven post-operatively. No short-term complications such as dyspnea or thyroid storm were found postoperatively. Post-operative follow up was done for 9 months to 6 years and no recurrence was observed.
Conclusion: Comprehensive pre-operative preparation, pre-operative evaluation, complete exposure of the operative field, meticulous operation, effective control and prevention of hemorrhage and prevention against damage to superior and recurrent laryngeal nerves are crucial for the successful surgical intervention of giant nodular goiter.
nodular goiter; peri-operative treatment; surgical intervention.