High risk and low prevalence diseases: Thyroid storm.

INTRODUCTION: Thyroid storm is a rare but serious condition that carries a high rate of morbidity and even mortality. OBJECTIVE: This review highlights the pearls and pitfalls of thyroid storm, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Thyroid storm is a challenging condition to diagnose and manage in the ED. It is characterized by exaggerated signs and symptoms of thyrotoxicosis and evidence of multiorgan decompensation, usually occurring in the presence of an inciting trigger. Clinical features of thyroid storm may include fever, tachycardia, signs of congestive heart failure, vomiting/diarrhea, hepatic dysfunction, and central nervous system disturbance. There are several mimics including sympathomimetic overdose, substance use disorders, alcohol withdrawal, acute pulmonary edema, aortic dissection, heat stroke, serotonin syndrome, and sepsis/septic shock. Ultimately, the key to diagnosis is considering the disease. While laboratory assessment can assist, there is no single laboratory value that will establish a diagnosis of thyroid storm. Clinical criteria include the Burch-Wartofsky point scale and Japan Thyroid Association diagnostic criteria. ED treatment focuses on diagnosing and managing the trigger; resuscitation; administration of steroids, thionamides, iodine, and cholestyramine; and treatment of hyperthermia and agitation. Beta blockers should be administered in the absence of severe heart failure. The emergency clinician should be prepared for rapid clinical deterioration and employ a multidisciplinary approach to treatment that involves critical care and endocrinology specialists. CONCLUSIONS: An understanding of thyroid storm can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Estimating Incidence and Case Fatality of Thyroid Storm in Germany Between 2007 and 2017: A Claims Data Analysis.

Background: Given the paucity of epidemiological studies on thyroid storm, we aimed to estimate the incidence rate and case fatality of thyroid storm in Germany based on a large claims database. Methods: Using the German Pharmacoepidemiological Research Database (GePaRD) we identified patients with at least one inpatient discharge diagnosis of thyroid storm (International Statistical Classification of Diseases and Related Health Problems, 10th revision, German modification; ICD-10-GM E05.5) between 2007 and 2017 and calculated age-standardized and age-specific incidence rates in males and females (no age restriction). We defined deaths occurring within 30 days of the diagnosis as thyroid storm-associated and determined case fatality by sex and age group. Point estimates were reported with confidence intervals [CIs]. Results: We identified 1690 patients with an incident diagnosis of thyroid storm. Of these, 72% were females (n = 1212). The mean age was 60 years (standard deviation: 18.6 years). The age-standardized incidence rate per 100,000 persons per year was 1.4 [CI 1.2-1.7] in females and 0.7 [CI 0.5-0.9] in males. In females ≤60 and >60 years of age, the incidence rate was 0.9 [CI 0.9-1.0] (males: 0.4 [CI 0.3-0.4]) and 2.7 [CI 2.5-2.9] (males: 1.7 [CI 1.5-1.9]), respectively. The case fatality of thyroid storm was 1.4% [CI 0.6-2.8] in females ≤60 years and 10.9% [CI 8.6-13.7] in females >60 years. In males, the case fatality was 1.0% [CI 0.2-4.0] in those aged ≤60 years and 16.7% [CI 12.6-21.7] in those >60 years. Conclusions: Incidence rates of thyroid storm were markedly higher in females than in males and were three times higher in persons >60 years compared with younger age groups. The case fatality was below 2% in persons aged ≤60 years and markedly higher in older persons (males: 17 times and females: 8 times).

Presentations and Outcomes of Thyroid Storm.

The aim of this study is to describe the characteristics and outcome of thyroid storm patients presenting at two tertiary care centres of Karachi, i.e. at Dow University of Health Sciences; and Liaquat National Hospital, Karachi, from December 2018 to May 2019. All patients between 18-70 years of age, who were admitted with thyroid storm and fulfilled the Burch- Wartofsky criteria, were inducted. Demographics including age, gender, clinical presentations, systemic symptoms, clinical examination of the thyroid and laboratory findings were reviewed from the file records to identify factors associated with mortality using the available data. Overall, five (62.5%) out of eight patients were female. The mean age was 43 ±1.67 years. Infections were the most common comorbid condition followed by cardiovascular and gastrointestinal diseases. The in-hospital mortality rate was 87.5% (n=07).

Thyrotoxic periodic paralysis: A retrospective, observational study from India.

Background & objectives: Thyrotoxic periodic paralysis (TPP) is an endocrine emergency presenting with acute-onset flaccid paralysis in a patient having thyrotoxicosis accompanied by hypokalaemia. This study was conducted to evaluate the clinical profile of patients with TPP presenting to three centres in India. Methods: This retrospective, observational study was conducted at three tertiary care Armed Forces medical centres, located at Lucknow, Kolkata and Delhi. The history, clinical features, treatment details and outcomes were evaluated. Results: Of the 244 patients with thyrotoxicosis, 15 were diagnosed with TPP and included in the study. These 15 patients (14 male and 1 female) had 32 episodes of TPP which were analyzed. The mean age was 30.2±6.2 yr (range: 21-39), and overt thyrotoxicosis was seen in all patients except one who had subclinical hyperthyroidism. Graves' disease was the most common cause of thyrotoxicosis (13/15) and the remaining two patients had subacute thyroiditis and gestational thyrotoxicosis. Hypokalaemia (serum potassium <3.5 mmol/l) was seen in 12 patients, and the mean serum potassium was 3.2±0.9 mmol/l (range: 2.1-4.9). All patients had flaccid weakness, predominantly involving the lower limb with no bulbar, respiratory or cranial nerve involvement. The average duration of paralysis was 10.6±5.7 h (range: 3-28 h). Interpretation & conclusions: Our study demonstrated an early age of presentation and presence of clinical and biochemical thyrotoxicosis in majority of patients with TPP. Hypokalaemia may not always be evident in patients with TPP.

Review article: Non-fatal strangulation: Hidden injuries, hidden risks.

Non-fatal strangulation (NFS) can be a cause of severe injury. However, the prevalence and rates of injuries from NFS are unknown, as few victims present to medical attention after strangulation. As up to 40% of fatal strangulations have no external signs, and the majority of surviving victims have few or minor injuries, finding those people severely injured remains challenging. The majority of the evidence regarding NFS is largely based on case reports and case series with no robust studies estimating rates of injuries or the best investigation tools. The injuries that are reported make clear that strangulation is a potentially lethal form of injury that should not be ignored in those presenting having been strangled, or in those presenting with neurological symptoms, including strokes, seizures and vascular abnormalities. The safety implications of strangulation are also important as it can be a prelude to homicide. A search of the literature was carried out with the following terms: Nonfatal strangulation (10), Nonfatal strangulation (17), 'Strangulation injuries' (19), 'Manual strangulation' (92) - laboratory testing eliminated, and 'choking game'. The PubMed database was used first, followed by the collections of Monash University and the Strangulation Institute (as some articles were too old to find electronically). This article summarises the injuries that can occur following strangulation and discusses the quality of the evidence thus far.

National Trends in Incidence, Mortality, and Clinical Outcomes of Patients Hospitalized for Thyrotoxicosis With and Without Thyroid Storm in the United States, 2004-2013.

BACKGROUND: Current evidence on the incidence and outcomes of patients with thyroid storm in the United States is limited to single-center case series. This study determined the national incidence of thyrotoxicosis with and without thyroid storm and clinical outcomes among hospitalized patients during a 10-year period in the United States. METHODS: Retrospective longitudinal analysis was conducted of clinical characteristics, mortality, hospital length of stay, and costs from 2004 to 2013. Adults (≥18 years of age) with a primary diagnosis of thyrotoxicosis with and without thyroid storm were included. To determine the incidence, outcomes, and cost of thyrotoxicosis with and without thyroid storm, the study used data from the National Inpatient Sample database, the largest public inpatient database, with a representative sample of all non-federal hospitals in the United States. RESULTS: Among 121,384 discharges with thyrotoxicosis during the study period (Mage ± standard error = 48.7 ± 0.11 years; 51.9% Caucasian; 77.3% female), 19,723 (16.2%) were diagnosed with thyroid storm. During the past decade, the incidence of thyroid storm ranged between 0.57 and 0.76 cases/100,000 U.S. persons per year, and 4.8 and 5.6/100,000 hospitalized patients per year. Thyroid storm was associated with significantly higher hospital mortality (1.2-3.6% vs. 0.1-0.4%, p < 0.01) and longer length of stay (4.8-5.6 vs. 2.7-3.4 mean days, p < 0.001) compared to patients with thyrotoxicosis without storm. Inflation-adjusted hospitalization costs progressively increased in patients with thyroid storm from $9942 to $12,660 between 2004 and 2013 (p < 0.01). CONCLUSIONS: One of every six discharges for thyrotoxicosis was diagnosed with thyroid storm. Thyroid storm is associated with a 12-fold higher mortality rate compared to thyrotoxicosis without storm. The incidence and mortality of thyroid storm has not substantially changed in the past decade. However, hospitalization costs have significantly increased.

Thyroid Storm: A Japanese Perspective.

BACKGROUND: Thyroid storm (TS) is life threatening. In the mid-2000s, its incidence was poorly defined, peer-reviewed diagnostic criteria were not available, and management and treatment did not seem to be verified based upon evidence and latest advances in medicine. METHODS: First, diagnostic criteria were developed based on 99 patients in the literature and seven patients in this study. Then, initial and follow-up surveys were conducted from 2004 through 2008, targeting all hospitals in Japan to obtain and verify information on patients who met diagnostic criteria for TS. Based on these data, the diagnostic criteria were revised, and management and treatment guidelines were created. RESULTS: The incidence of TS in hospitalized patients in Japan was estimated to be 0.20 per 100,000 per year and 0.22% of all thyrotoxic patients. The mortality rate was 10.7%. Multiple organ failure was the most common cause of death, followed by congestive heart failure, respiratory failure, and arrhythmia. In the final diagnostic criteria for TS, the definition of jaundice as serum bilirubin concentration >3 mg/dL was added. Based upon nationwide surveys and the latest information, guidelines for the management and treatment for TS were extensively revised and algorithms were developed. CONCLUSIONS: TS remains a life-threatening disorder, with >10% mortality in Japan. New peer-reviewed diagnostic criteria for TS are presented and its clinical features, prognosis, and incidence are clarified based on nationwide surveys. Furthermore, this information helped to establish detailed guidelines for the management and treatment of TS. A prospective prognostic study to validate the guidelines is eagerly anticipated.

Trends in the Incidence and In-Hospital Outcomes of Cardiogenic Shock Complicating Thyroid Storm.

BACKGROUND: Thyroid storm (TS) constitutes an endocrine emergency with an incidence of up to 10% of all admissions for thyrotoxicosis. Cardiogenic shock (CS) is a rare complication of TS and very limited data exists on its incidence and outcomes. We aimed to estimate the national trends in incidence and outcomes of CS among patients admitted to US hospitals with TS. MATERIALS AND METHODS: We queried the nationwide inpatient sample for patients with the discharge diagnosis of TS between the years of 2003 and 2011. RESULTS: Based on a weighted estimate, we identified 41,835 patients with a diagnosis of TS, of which 1% developed CS. Patients with CS were more likely to have history of atrial fibrillation, alcohol abuse, preexisting congestive heart failure, coagulopathy, drug use, liver disease, pulmonary circulation disorders, valvular disorders, weight loss, renal failure, fluid and electrolyte disorders as compared to those who did not develop CS (P < 0.001 for all). We observed an increase in incidence of CS from 0.5% in 2003 to 3% in 2011 and a decrease in mortality from 60.5% in 2003 to 20.9% in 2011 (Ptrend < 0.001 for both). CONCLUSIONS: We observed that CS is a rare complication of TS, which occurs more commonly in male patients with preexisting structural and atherosclerotic heart disease, and carries a very poor prognosis. Although incidence has increased over the years, mortality from CS has steadily declined.

Short-term preoperative octreotide treatment for TSH-secreting pituitary adenoma.

Preoperative control of hyperthyroidism in patients with TSH-secreting pituitary adenomas (TSHoma) may avoid perioperative thyroid storm. Perioperative administration of octreotide may control hyperthyroidism, as well as shrink tumor size. The effects of preoperative octreotide treatment were assessed in a large number of patients with TSHomas. Of 81 patients who underwent surgery for TSHoma at Toranomon Hospital between January 2001 and May 2013, 44 received preoperative short-term octreotide. After excluding one patient because of side effects, 19 received octreotide as a subcutaneous injection, and 24 as a long-acting release (LAR) injection. Median duration between initiation of octreotide treatment and surgery was 33.5 days. Octreotide normalized free T4 in 36 of 43 patients (84%) and shrank tumors in 23 of 38 (61%). Length of octreotide treatment did not differ significantly in patients with and without hormonal normalization (p=0.09) and with and without tumor shrinkage (p=0.84). Serum TSH and free T4 concentrations, duration of treatment, incidence of growth hormone (GH) co-secretion, results of octreotide loading tests, form of administration (subcutaneous injection or LAR), tumor volume, and tumor consistency did not differ significantly in patients with and without hormonal normalization and with and without tumor shrinkage. Short-term preoperative octreotide administration was highly effective for TSHoma shrinkage and normalization of excess hormone concentrations, with tolerable side effects.

[Diagnosis and treatment of thyroid storm].

Thyrotoxic storm is a life-threatening condition requiring emergency treatment. Neither its epidemiological data nor diagnostic criteria have been fully established. We clarified the clinical and epidemiological characteristics of thyroid storm using nationwide surveys and then formulate diagnostic criteria for thyroid storm. To perform the nationwide survey on thyroid storm, we first developed tentative diagnostic criteria for thyroid storm, mainly based upon the literature (the first edition). We analyzed the relationship of the major features of thyroid storm to mortality and to certain other features. Finally, based upon the findings of these surveys, we revised the diagnostic criteria. Thyrotoxic storm is still a life-threatening disorder with over 10% mortality in Japan.

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

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.

[Thyroid storm--thyrotoxic crisis: an update]. / Thyreotoxische Krise--ein Update.

Thyroid storm or thyrotoxic crisis is a rare but life-threatening condition requiring immediate treatment, preferably in an intensive care unit. Its incidence is about 1-2% among patients with overt hyperthyroidism. A thyrotoxic crisis occurs predominantly in the elderly and is three to five times more common in women than in men. The overall mortality is 10-20%. Even though the pathogenesis is still not fully understood, an increased sensitivity to catecholamines appears to be an important mechanism, and a number of endogenous and exogenous stress factors that can provoke the onset of a thyrotoxic storm have been identified. The diagnosis of a thyrotoxic crisis is made entirely on the clinical findings. Most importantly, there is no difference in thyroid hormone levels between patients with "uncomplicated" thyrotoxicosis and those undergoing a thyroid storm. Any delay in therapy, e.g. by awaiting additional laboratory results, must be strictly avoided, because the mortality rate may rise to 75%. Thus early thyroidectomy should be considered as the treatment of choice, if medical treatment fails to result in clinical improvement. Medical treatment is based on three principles: 1) counteracting the peripheral effects of thyroid hormones; 2) inhibition of thyroid hormone synthesis; and 3) treatment of systemic complications. These measures should bring about clinical improvement within 12-24 hours. If death occurs it is most likely to be cardiopulmonary failure, particularly in the elderly.

Is it safe to treat hyperthyroid patients with I-131 without fear of thyroid storm?

OBJECTIVES: Thyroid storm is extremely rare. However, hyperthyroid patients with severe thyrotoxicosis are frequently not treated immediately with I-131 for fear of thyroid storm but are placed on thiouracil drugs for varying periods of time. We demonstrate herein that it is safe to treat these patients with 1-131, without pretreatment with thiouracil drugs, provided they do not have complicating intercurrent disease. Our definition of severe hyperthyroidism includes marked signs and symptoms of thyrotoxicosis, suppressed TSH, markedly elevated free T4 and/or free T3 and elevated radioactive iodine uptake (RAIU) (>30%) at 4 or 24 hours. Our diagnostic criteria for thyroid storm include two or more findings of fever (>38 degrees C, 100 degrees F), severe tachycardia, high pulse pressure, agitation with tremors, flushing, sweating, heart failure, nausea, vomiting, diarrhea, jaundice associated with high free T4 and/or free T3. METHODS: Patients were selected retrospectively for the period between August 2003 and December 2004. One hundred and twenty-two patient visits were identified. These patients were treated with 370-740 MBq (10-20 mCi) of I-131 and were evaluated for any evidence of thyroid storm. Most of the patients were placed on beta blocker drugs at the time of initial I-131 therapy; these were continued for at least two months, when the first follow-up visit occurred. At the time of I-131 therapy, it is our policy to educate the patients to seek immediate medical attention for exacerbation of symptoms of thyrotoxicosis. RESULTS: Not one of these patients developed thyroid storm. A subset of 25% of these cases with higher potential for thyroid storm (RAIU more than 65%, very marked signs and symptoms, and very markedly elevated free T4 and/or free T3) also tolerated the I-131 therapy well with marked clinical improvement and no exacerbation of the thyrotoxic state. CONCLUSION: It is safe to administer I-131 to patients who are severely hyperthyroid without fear of thyroid storm, provided beta blockade drugs are used to control the signs and symptoms; patient education is also important. With these steps, 4-6 weeks of prior medical treatment may not be necessary.