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Lithuanian University of Health Science
MEDICAL ACADEMY
FACULTY OF MEDICINE
Ilona Chorny
Diagnosis and Management of Thyroid Storm in Emergency Department
Department of Disaster Medicine
Scientific Supervisor:
Prof. Dinas Vaitkaitis
Kaunas, Lithuania 2018-2020
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Table of content
Table of content ... 2
1. SUMMARY ... 3
2. Conflict of Interest... 4
3. CLEARANCE ISSUED BY THE ETHICS COMMITTEE ... 5
4. ABBREVIATIONS ... 6
5. INTRODUCTION ... 7
6. AIM AND OBJECTIVE OF THE THESIS ... 8
7. REASERCH METHODOLOGY AND METHODS ... 9
8. RESULTS AND THEIR DISSCUSION ... 10
8.1 Prevalence and causes of death in thyroid storm patients ... 11
8.2 Precipitating factors and common features among patients who went through thyroid
storm ... 13
8.3 Appropriate guidelines for diagnosis of TS based on clinical findings ... 17
8.4 Appropriate guidelines for the treatment of TS based on clinical findings ... 20
9. CONCLUSION ... 27
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1. SUMMARY
Author: Ilona Chorny
Title: Diagnosis and Management of Thyroid Storm in Emergency Department
Introduction: Thyroid storm (TS) is an endocrine emergency condition that until nowadays remains a
diagnostic and therapeutic challenge for many physicians. Many precipitating factors are related to the development of TS. Clinical features are the sole base for scoring system and treatment should be initiated immediately in order to decrease mortality rate (1).
Research aim: To list and discuss about thyroid storm manifestations as an emergency, life threatening
condition and to point on important hallmarks that will aid in diagnosis and treatment.
Objectives:
1. To find out the prevalence and causes of death in thyroid stormed patients.
2. To find out correlation between precipitating factors and thyroid storm events and commonest features among patients who went through thyroid storm.
3. To propose appropriate guidelines for diagnosis of thyroid storm based on clinical findings. 4. To propose appropriate guidelines for treatment of thyroid storm based on clinical findings.
Methodology: systematic review that analyzed different research works and publications in the last 10
years in the English language. Using PubMed Medline research engine and Google scholar.
Results and Conclusion: Thyroid storm is one of the most dangerous life-threatening disorders that
requires proper understanding, diagnosis and management in order to decrease the prevalence and mortality rate. Nowadays there are specific guidelines for diagnosis and treatment of TS.
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2. Conflict of Interest
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3. CLEARANCE ISSUED BY THE ETHICS COMMITTEE
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4. ABBREVIATIONS
TS- thyroid storm
CNS- central nervous system GI- gastrointestinal
TSH- thyroid stimulating hormone DKA- diabetic ketoacidosis
TSI- thyroid stimulating immunoglobulins CBC- complete blood count
GCS- Glasgow coma scale CHF- chronic heart failure
DIC- disseminated intravascular coagulation BWPS- Burch-Wartofsky Point Scale JTA- Japanese Thyroid Association ATA- American Thyroid Association JRC- Japan Resuscitation Council PTU- propylthiouracil
TPE- Therapeutic plasmapheresis IV- Intravenous
AF- Atrial fibrillation PPI- Proton pump inhibitors
H2A- histamine 2 receptor antagonists
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5. INTRODUCTION
In 1926 Thyroid storm (TS) was described by Lathey as ‘’the crisis of exophthalmic goiter’’ because of significant number of patients that presented with underlying exacerbation of their Graves disease. This exacerbation referred as thyrotoxic crisis. Over the years physicians straggled to correctly describe all the physiological changes in this diagnosis. In 1993, Burch and Wartofsky evolve a scoring system for diagnosis standardization. Today around the world physicians are trying to establish clear diagnostic criteria that are based on universal clinical parameters, this are important for reducing
morbidity and mortality associated with thyroid storm. This condition requires aggressive treatment and thus complete and rapid evaluation might save the patient.(1)
In order to appreciate the reasonable treatment behind thyroid storm it is necessary to understand the normal thyroid hormone physiology. Feedback mechanisms through hypothalamus, anterior pituitary and thyroid gland are the main regulators of normal thyroid function. Hypothalamus release into anterior pituitary the thyrotropin-releasing hormone (TRH) that stimulate the release of thyroid-stimulating hormone (TSH) which eventually bind to a specific receptor on thyroid cells that in turn will release into the circulation after few biochemical processes the biologically active hormones, thyroxine (T4) and triiodothyronine (T3). Peripheral thyroid hormone inhibit synthesis and release of TSH and TRH by negative feedback loop.(1)
Thyroid storm is a rare consequence of thyrotoxicosis that is associated with significant
morbidity and mortality. Its remains difficult to completely understand this particular condition due to the rarity, nonspecific symptomatology and the alterations in diagnosis and treatment strategies.(2)
An overview of the literature may aid in the practical as well as the theoretical significance of the work done in this field so far. The aim of this study is to systematically review the latest work done in the field of Thyroid Storm, its diagnosis and management.
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6. AIM AND OBJECTIVE OF THE THESIS
Research aim: To list and discuss about thyroid storm manifestations as an emergency, life threatening
condition and to point on important hallmarks that will aid in diagnosis and treatment.
Objectives:
1. To find out the prevalence and causes of death in thyroid stormed patients.
2. To find out precipitating factors and commonest features among patients who went through thyroid storm.
3. To propose appropriate guidelines for diagnosis of thyroid storm based on clinical findings. 4. To propose appropriate guidelines for treatment of thyroid storm based on clinical findings.
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7. REASERCH METHODOLOGY AND METHODS
In this systematic review PRISMA 2009 statement and check list were used as the main resource for research methodology. The main search engine was MEDLINE PubMed and Google Scholar and that yielded about 2619 research works. Randomized clinical trials, retrospective studies, systematic and literature reviews were used. Inclusion and exclusion criteria navigated which works should or shouldn’t be used.
Information source:
MEDLINE PubMed online research engine and Google Scholar
Inclusion criteria:
Terms used: Thyroid storm, endocrine emergency, emergency department, thyrotoxicosis, mortality rate, prevalence, precipitating factors, diagnosis guidelines, treatment guidelines.
Sentences used:
- Prevalence in thyroid storm
- Precipitating factors in development of thyroid storm - Common features in thyroid storm
- Death in thyroid storm - Diagnosis of thyroid storm - Treatment of thyroid storm
Exclusion criteria:
- Works written not in English language - Not relevant title or abstract
- Research work not more than 30% that wasn’t published in the last 10 years
Data collection process:
The initial search in PubMed yielded 2619 results, which were reduced to 325 after using filters such as published in the last 10 years and only English language. Using the best match function in PubMed helped review the title and abstract of each work and select the most appropriate once which were 95 overalls. After full review of the text 28 research works were included into this systematic review.
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Fig.1. Inclusion and exclusion flow chart that describes the data collection process
2,619 works found on initial search of terms and sentences
325 titles and abstracts were reviewed
95 full text reviews was done
28 studies were included in this literature review
2,294 works were excluded based on exclusion criteria
67 studies were excluded based on bias inappropriate
statistical analysis and duplication of information
230 works were excluded based on title and abstract
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8. RESULTS AND THEIR DISSCUSION
8.1
Prevalence and causes of death in thyroid storm patients
The prevalence of TS was not fully investigated until the mid-2000s in a large population. One report found that no more than 1-2% of TS is a consequence of thyrotoxicosis(3) and the mortality rate ranging from 10% to 75%.
The Japanese conducted and published two large studies about TS with national representative population of patients.(4)
The first study was done from 2004 to 2008 with nationwide surveys in order to evaluate the incidence of TS. The incidence rate assessed to be 0.20 persons per 100,000 population per year,
accounting for 0.22% of all thyrotoxic patients and 5.4% among hospitalized patients with thyrotoxicosis with a hospital mortality of 9.5‐ 11%. In between 2007-2008 the incidence of TS increased in
endocrinology departments but not in emergency departments probably due to an increase awareness of TS throughout the years.(5)
The second study was done in a period of two years and concluded an incidence of 6.3 per 100,000 hospitalized patients with a mortality rate of 10.1%.(4)
In United States a single study was performed and reported TS incidence of about 16.7% with patients hospitalized with confirmed thyrotoxicosis.(4)
TS is more common among women compared to men and more frequently observed in patients with Graves disease, but older population of patients with TS may have autonomous nodular disease. Over the years there has been more frequent screening for thyroid disorders that led to earlier diagnosis and improvement in thyroid storm incidence. In addition, surgically induced thyroid storm frequency reduced due to better preparation of patient prior to surgery.(1)
Thyroid storm is a rare life-threatening metabolic crisis and the predictive features associated with survival or mortality are still not completely understood.
In Japanese hospitals the reported mortality rates due to TS varied widely: 10.7% (38 of 356 patients), 25% ( 7 of 28 patients), and 8% (2 of 25 patients). (22,2)
Japan Thyroid Association suggested that shock, disseminated intravascular coagulation (DIC) and multiple organ failure were associated with mortality in patients with TS, but did not include
12 microdata of individual patients. Therefore, factors that are associated with mortality are not completely defined yet.(21)
According to one observational study that was conducted on TS patients using Japanese national inpatient database, 1324 patients were diagnosed with TS between April 1, 2011 and March 31, 2014. As indicated in this study, overall, in-hospital mortality rate is 10.1%. Older age (>60), CNS disfunction at the time of admission to the hospital, lack of proper use with anti-thyroid drugs and beta-blockers and also the necessity of mechanical ventilation and therapeutic plasma exchange and hemodialysis are all
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8.2 Precipitating factors and common features among patients who went through
thyroid storm
Thyroid storm patients have multiple precipitating factors related to the development of TS. Thyroid pathology, pregnancy, thyroid surgery, drugs, trauma, stress, infections, DKA and hypoglycemia can all precipitate TS and cause life threatening conditions.(6)
Thyroid storm represents the radical manifestation of thyrotoxicosis while thyrotoxicosis related to any reason of excessive thyroid hormone concentration. The moment when thyrotoxicosis becomes TS is controversial and subjective. Most common cause of thyrotoxicosis in case of TS is Graves’ disease. In Graves disease will be excess of thyroid hormones due to thyrotropin receptor antibodies action on thyroid gland. Commonly occurs in young women but can occur in any age and sex.(7)
TS may also be a consequence of other thyroid pathologies that will cause thyrotoxic condition including destructive thyroiditis, solitary toxic adenoma, toxic multinodular goiter, TSH-secreting pituitary adenoma, hCG-secreting hydatidiform mole or metastatic thyroid cancer.(8)
In the past the most common cause of TS was thyroid surgery. Nowadays due to proper recognition and preparation before thyroid surgery TS incidence reduced significantly.(7,1)
Infections is another very common precipitating factor among people with TS, particularly upper respiratory tract infections, for example Influenza A(9) and streptococcal infection.
During normal pregnancy thyroid gland can enlarge by 50% due to hyperplasia of glandular tissue and increase in vascularity. Pregnant women have a normal but reversible hormonal change resulting in the increase of T3 and T4 release from thyroid gland, although TSH level stay normal. However, it’s important not to miss pathological changes like goiter or thyromegaly. During pregnancy women will have an increased cardiac output, pulse and heat intolerance due to elevation of 25% in basal metabolic rate. Maternal TSH can not cross placenta however, thyroid stimulating immunoglobulins (TSIs) can cross placenta and stimulate the production of thyroid hormone by the fetus and can lead to hyperthyroidism in fetal or neonate. Physicians need to be aware about additional signs and symptoms of hyperthyroidism during pregnancy that are not related to the normal hypermetabolic state during
pregnancy, for example, hyperemesis, diarrhea, heart rate above 100/min that will not decrease with Valsalva maneuver and/or lymphadenopathy.(10)
14 Pregnant women have an occurrence of 1% to 2% of thyroid storm due to predisposing
hyperthyroidism. Preceding events associated with TS during pregnancy include preeclampsia, surgery, trauma, infection, ketoacidosis and stress. Perhaps the presenting signs and symptoms are nonspecific and can be confused with other medical conditions and a high clinical suspicion is required. Preeclampsia can make the diagnosis of TS complicated due to a number of symptoms including elevated blood pressure, abdominal pain, headache and heart failure. More apparent signs of hyperthyroidism as thyroid bruit and goiter are specific for thyroid dysfunction. During pregnancy moderate compensated respiratory alkalosis may occur and have to be considered during acid base status interpretation. Fetal tachycardia and late decelerations may develop because of metabolic changes and eventually lead to increased fetal morbidity and mortality. Laboratory analysis of TSH, free T3, free T4, complete blood count (CBC) and metabolic panel are necessary. On metabolic panel screening may have electrolyte disturbances, hyperglycemia, hypercalcemia and leukocytosis. There are no generally accepted levels at which diagnosis of TS guaranteed and may have significant laboratory overlap with simple hyperthyroidism.(11)
TS may be associated with trauma but, emergency care physicians are straggling to recognize the condition due to focusing more on obvious injuries. Proper investigation of patient history and associated risk factors that related to TS can decrease the incidence of misdiagnosed cases and prevent fatal
outcomes. Patients with hyperthyroidism has a greater risk to develop TS after trauma. TS are not directly related to severity and location of the trauma. Incidence of TS are almost equal between blunt direct thyroid trauma and injuries far away from thyroid gland (ex. abdomen, chest). TS after blunt injury to thyroid gland can be caused by hormone release into circulation from ruptured acini but the mechanism of distant organ injury relation to TS is still unknown although emotional stress induced by anxiety or pain after trauma may have a role in the development of TS as it is considered as precipitant of TS.
Tachycardia, fever, altered consciousness are the most common symptoms of posttraumatic TS and patients may have a severe signs and symptoms of hyperthyroidism containing central nervous system (CNS) symptoms, fever, gastrointestinal (GI) and hepatic dysfunction, cardiovascular manifestations and acute renal failure. Most patients with post traumatic TS have laboratory tests similar to hyperthyroidism including low TSH and elevated T4 and T3. (12)
Many drugs may precipitate the development of TS, among those drugs are Levothyroxine, Liothyronine, Amiodarone, Ipilimumab, Nivolumab and also Radioiodine therapy.(8)
Levothyroxine (manufactured form of thyroxine)and Liothyronine (manufactured form of triiodothyronine) are usually prescribed for hypothyroid state or thyroid suppression test. Sometimes
15 people using thyroid hormone off-label for weight reduction, controlling depressive mood or for various somatic symptoms. Uncontrolled intake of liothyronine can cause lethal TS. The integration of
excessively elevated T3, low T4 and extremely low TSH and TG may put down the conclusion of prolonged liothyronine intoxication.(14)
Amiodarone is a class 3 antiarrhythmic drug used for life threatening arrhythmias. For the control of sinus rhythm in patients with atrial fibrillation and for prevention of recurrent ventricular arrhythmias(15). Amiodarone is 40% iodine by weight and these can result in hypothyroidism (by Wolff-Chaikoff effect) or thyrotoxicosis (by providing iodine for excess hormone production when underlying thyroid abnormalities are present or by direct toxic effect of drug on the thyroid gland leading to
destructive thyroiditis).(16)
Immune checkpoint inhibitors as Ipilimumab and Nivolumab are used for the treatment of advanced melanoma, nevertheless they can cause immune related adverse events especially with combination immunotherapy. TS can develop from such combination therapy.(17)
Radioiodine therapy may be another precipitating factor for the development of TS. Radioiodine therapy may induce thyroiditis and subsequent fibrosis that will lead to destruction of follicular cells inside the thyroid gland and as a consequence rapid release of stored thyroid hormone into circulation.(18)
TS as a life-threatening condition has multiple precipitating factors common to different patients as well as many common features shared by TS patients.
Frequency of TS is higher in women, with the ratio of female: male of approximately 3:1.(8) Patients with definitive TS, suspected TS and thyrotoxicosis but not TS have very similar clinical manifestations. Most of the patients with TS has elevated body temperature above 38 degrees, HR above 130bpm and most of the patients have abnormal Glasgow coma scale (GCS). Gastrointestinal (GI) and hepatic manifestations are also presented in majority of TS patients. Chronic heart failure (CHF) features and atrial fibrillation (AF) may also be present.(5)
TS patients have a diversity of clinical presentations however, few of those presentations are universal and very common. Severe high body temperature may induce abundant sweating and contribute to fluid loss, a clinical finding that help in the differentiation of TS from thyrotoxicosis. Usually
tachycardia prone to be out of proportion to the underlying pathology. In the settings of TS cardiac manifestations as palpitation, tachycardia, widened pulse pressure, dyspnea and atrial fibrillation may become life threatening. Combination of increased cardiac output, arrhythmias and symptoms of heart
16 failure may progress to cardiovascular collapse and shock. Central nervous system (CNS) symptoms regularly seen and presented as delirium, agitation, confusion to stupor and may progress to coma(19). It is worth mention that sometimes TS can be misdiagnosed as Psychosis due to similar presentation. Mental status alterations associated with TS and deterioration of psychosis may be indistinguishable hence, if patients have no history of thyroid disease and thyroid hormone levels were not measured their TS may be ignored and not diagnosed.(20)
Patients may also present with GI manifestations including diarrhea, nausea and vomiting what may contribute more to fluid loss. Hepatomegaly secondary to hepatic congestion may also be seen. Jaundice development has a poor prognosis for the patient.(19)
From 2004 to 2008 Japanese hospitals were surveyed for cases of TS. Clinical and laboratory data were obtained. More than 75% of patients had tachycardia greater than 130bpm, 84% of patients had CNS symptoms, 69% had GI manifestations and 40% of patients had heart failure. In all, 76% of the patients with TS had more than 3 major organ manifestations.(21)
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8.3 Appropriate guidelines for diagnosis of TS based on clinical findings
Thyroid storm is an endocrine emergency requiring immediate diagnosis in order to decrease mortality rate. Biological markers that are beneficial for the diagnosis of TS are not based and clinical symptoms are not always indistinguishable from other thyroid pathologies. Burch-Wartofsky Point Scale (BWPS) for the diagnosis of TS was introduced in 1993, this scoring system uses the severity of
symptoms of multiple organ decompensation and the contribution of precipitating factors. BWPS was used for more than 2 decades (Fig.2). (24)
18 Above criteria include hyperpyrexia, tachycardia, arrhythmias, congestive heart failure, agitation, delirium, psychosis, stupor, and coma, as well as nausea, vomiting, diarrhea, hepatic failure, and the presence of an identified precipitant. Points in the BWPS system are based on the severity of individual manifestations, with a point total of equal or more than 45 consistent with TS , 25–44 points classified as impending TS, and less than 25 points making TS unlikely. (24,6)
Japanese Thyroid Association (JTA) proposed in 2012 new diagnostic evaluation criteria for TS. In these criteria, existence of thyrotoxicosis is necessary as precondition and definite and likely TS diagnosis is based on specific combinations of symptoms similar to the list in BWPS criteria to assign patients to the diagnostic categories of TS1 or TS2 (Fig.3).
19 JTA criteria has one feature that contribute to the diagnosis of TS more than other organ
symptoms, this particular feature is disturbances of consciousness.(25)
Data comparing these two diagnostic systems suggest an overall agreement, but there is a tendency for underdiagnosis using the JTA categories compared to a BWPS.
In one study involving 25 patients with clinical diagnosis of TS the BWPS more than 45 were calculated in 20 patients and 25-44 score in 5 patients, but these 5 patients were not identified by JTA criteria system. However, among 125 hospitalized patients with clinical diagnosis of compensated
thyrotoxicosis but not TS, 27 patients had a score more than 45 points according to BWPS and 21 patients using JTA score had either TS1 or TS2, suggesting similar rates of overdiagnosis with the two systems. Diagnosis of TS is still remaining clinical and is augmented by current diagnostic systems. BWPS seem to be more sensitive than the JTA classification of TS1 or TS2 in recognizing patients with a clinical
diagnosis of TS, but patients with BWPS of 25-44 describe a group in which the decision to apply
aggressive treatment should be based on clinical judgment and not only based on the diagnostic criteria in order to prevent over treatment and drug toxicity. Those patients in this category are recommended to be observed for deterioration possibility. Whatever system is chosen care should be taken in order to prevent inappropriate management to a patients without severe thyrotoxicosis because TS manifestations except hyperpyrexia could also be recognized in any major illness, which many of them are known to precipitate TS. (26)
Both BWPS and JTA criteria are recommended in order to properly diagnose TS and to decrease mortality rates. Application of either criteria system should be done correctly in order to prevent
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8.4 Appropriate guidelines for the treatment of TS based on clinical findings
TS treatment have multiple aims: 1. Supportive care
2. Treatment facing thyroid hormone synthesis and secretion
3. Means of decreasing thyroid hormone action in peripheral tissue (β-adrenergic receptor blockade and preventing conversion of T4 to T3 in periphery)
4. Change systemic decompensation
5. Care about precipitating factors or intercurrent diseases 6. Definitive treatment:
21 Patients with TS may safer from fluid losses due to vomiting, diarrhea, sweating and fever. In order to control the fluid loss patients may receive normal saline with or without dextrose (isotonic saline with 5% or 10% dextrose) according to blood glucose measurements.(6)
In order to control thyroid hormone synthesis Thionamides are used. Methimazole or
propylthiouracil (PTU) are both Thionamides that reduce synthesis of new hormone generation (also have immunosuppressive effects). Those medications prevent organification and by directly inhibit thyroid peroxidase through the coupling of iodotyrosine in thyroglobulin molecules. Methimazole have longer duration of half-life compering to PTU and display a free form in serum while PTU is 80-90% bound to albumin. According the American Thyroid Association (ATA) PTU is more recommended then
Methimazole because PTU in large doses decrease T3 levels more than Methimazole.(26,1)
However, according a nationwide survey performed by the JTA revealed that conversion of T4 to T3 may be already suppressed in severe TS and also there is no meaningful distinction in TS severity or mortality among patients using Methimazole or PTU. Therefore, Methimazole like PTU may be practical in severe TS (where there is decreased T4 to T3 conversion) (24)(26). JTA guidelines recommend
Methimazole as the first-choice treatment for compensated Graves’ disease, except during early pregnancy, this recommendation is based on randomized prospective study carried out in Japan and showed that Methimazole normalized thyroid hormone levels quicker than PTU. This study also revealed that patients using Methimazole has lower adverse effects than patients using PTU.(27)
The latest American Association of Clinical Endocrinologist/American Thyroid Association guidelines recommend a 500 to 1000 mg loading dose of PTU followed by 250 mg every 4 hours and 60 to 80 mg per day of methimazole in divided doses. (26)
When GI tract is completely compromised and neither oral or rectal routes are appropriate for medication administration, Thionamides may be prepared for intravenous (IV) administration. IV preparations of Methimazole are commercially available in some countries, including Japan and some European countries, but not in the United States or United Kingdom. However, even in countries where commercially available, IV Methimazole may not be in stock in hospital pharmacies due to the rarity of their use. In US have been reports of preparing Methimazole injections in hospital pharmacies and cases of successful treatment with Methimazole injections in patients refractory to oral therapy. In some centers, only Carbimazole is available, which is the pro-drug of Methimazole and if Methimazole is not available, Carbimazole can be used with the same potency.(24)(6)
22 Lugol solution, potassium iodide, or ipodate may be delivered to cease thyroid hormone release. Thionamide therapy instituted first and these drugs given at least 1 h later. Iodine therapy blocks the release of prestored hormone and decreases iodide transport and oxidation in follicular cells. Two large prospective trials performed in Japan found that large doses of Inorganic Iodide administered together with Thionamides to Graves’ patients complicated with TS is recommended. In cases were iodine is contraindicated, Lithium may be used. Lithium inhibits thyroid hormone release from the thyroid gland and decreasing thyroid hormone synthesis. The dose of Lithium is 300 mg every 8 h and it should be monitored to prevent toxicity.(24,6)
β-adrenergic stimulation is increased in patients with TS, therefor adrenergic blockade is part of treatment plan both uncomplicated and complicated hyperthyroidism, including TS. Propranolol a nonselective beta blocker is the most commonly used in TS and also has the ability to decrease T4 to T3 conversion in the peripheral tissue. Recommended dose can be higher the usual due to increase drug metabolism in TS and can be as high as 60 to 120 mg orally every 6 hours. Propranolol can be used IV for quicker response or Esmolol a short acting beta blocker may be an alternative. IV Propranolol dose is 0.5 to 1.0 mg slow IV push initially and then 1 to 2 mg at 15-minute intervals while monitoring the heart rate.(1)
Corticosteroids are given as prophylaxis for relative adrenal insufficiency caused by the hypermetabolic state in TS. It has been shown that high doses can inhibit synthesis of thyroid hormone and conversion of T4 to T3 in the peripheral tissue. According some analysis in patients who were using corticosteroids in TS management have higher mortality and disease severity compared to those who didn’t use them. Hydrocortisone recommended dose is 300 mg/day (100 mg administered intravenously every 8 hours), another option is dexamethasone 8 mg/day. There is no evidence that Prednisolone or Methylprednisolone are better than Hydrocortisone or Dexamethasone. Corticosteroid doses should be modified according individual basis. There should be appropriate monitoring and prevention of side effects for instance hyperglycemia, peptic ulcer, and infection. Doses of Corticosteroids need to be decreased and stopped after confirmation of adrenocortical recovery.(24)
23 TS patients with high fever should be managed with Acetaminophen and cooling blankets or ice packs (Fig.5).
Fig.5. Schematic representation of treatment of fever in TS (24).
In case of clinical improvement of TS patients is not achieved in 24-48 hours after treatment with Thionamides, Inorganic Iodine, Beta clockers or Corticosteroids as well as treatment of triggering
condition and TS complications, Therapeutic plasmapheresis (TPE) should be considered. TPE replace the serum proteins to which almost 99% of thyroid hormones are bound. There are no prospective studies that confirm usefulness of TPE but, many case reports from Japan and other countries showed successful treatment of TS patients with PTE.(28,24)
When TS patients demonstrate clinical improvement with treatment they should be modulated or withdrawn. Thionamide are needed for few weeks to months after TS to reach euthyroidism, Iodine therapy may be discontinued, Glucocorticoids tapered and Beta blockers are indicated while patients are thyrotoxic. Definitive therapy with radioactive Iodine ablation may be required to prevent future
24 TS may present with CNS manifestations including restlessness, delirium, psychosis,
somnolence, convulsion, and coma. Treatment of thyrotoxicosis is most effective in controlling CNS manifestations, however the 2010 Japan Resuscitation Council (JRC) guidelines, Guidelines for
Psychiatric Emergency Treatment and 2010 Guidelines for Epilepsy Treatment have been based in Japan for the treatment of CNS symptoms. Glucose is given when hypoglycemia determined and vitamin B1 is used in case of malnutrition. (Fig.6)
25 Differential diagnosis of meningitis, cerebrovascular disease, metabolic disorders or poisoning should be ruled out (Fig.7).
Fig.7. Differential diagnosis of central nervous system manifestations in TS patients. (24)
First-line drugs for restlessness, delirium, and psychosis for patients who can tolerate oral medications are second-generation antipsychotics such as risperidone and olanzapine and for those who can not first-generation antipsychotic drugs such as haloperidol (should be used carefully due to unknown mechanism that can precipitate TS) and olanzapine by intramuscular or intravenous injection are used.(24)
Recommendations for treatment of tachycardia and atrial fibrillation (AF) are highly important in TS patients. Selective beta blockers such as bisoprolol (oral) are used for tachycardia less than 150 bpm and esmolol or landiolol (IV) are the first choice for tachycardia above 150 bpm in TS patients. Digitalis are used for AF in patients without severe renal impairment. When hemodynamics is impaired due to AF, cardioversion is recommended when left atrial thrombus ruled out. Class IA and IC antiarrhythmics are recommended to keep sinus rhythm after cardioversion. Anticoagulants should be considered when there is a risk for stroke.(24)
26 Treatment of GI disorders and hepatic injury in TS patients also should be treated. Treatment of GI infection are done parallel to thyrotoxicosis. Proton pump inhibitors (PPIs) or histamine 2 receptor antagonists (H2As) are indicated. TS patients may suffer from hepatotoxicity with or without jaundice and caused due to hepatocyte damage during thyrotoxicosis, according nationwide surveys total bilirubin equal or above 3.0 mg/ dL suggest worse prognosis. Based on the origin of hepatic dysfunction treatment should be introduced, comprising TPE for acute hepatic failure. TS causes muscle weakness in the diaphragm, esophagus, and contribute to gastric wall motility dysfunction and leads to nausea, vomiting and abdominal pain.(24)
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9. CONCLUSION
1. Thyroid storm prevalence and mortality rate has been reduced over the years due to better diagnosis and treatment.
Multiple precipitating factors were identified related to TS development, among them the most important is thyroid pathology, other include pregnancy, trauma, infections, DKA, stress, drugs and more.
2. TS is more common in females than males. The most common presentation of TS include fever above 38 degrees, HR above 130bpm and abnormal GCS. GI, hepatic, cardiovascular and CNS symptoms are also related to TS manifestations.
3. More than two decades BWPS were used for diagnosis of TS. In 2012 JTA proposed new diagnostic evaluation criteria based on the specific combinations of symptoms similar to the list in BWPS criteria and defined thyrotoxicosis as necessary precondition for TS development. According to data compering the two systems there are an overall agreement, but there is a propensity to underdiagnose using the JTA compared to BWPS, but the two are recommended for diagnosis as long as the application of either criteria done correctly.
4. TS treatment have multiple aims including supportive care, treatment facing thyroid hormone synthesis and secretion, means of decreasing thyroid hormone action in peripheral tissue (β-adrenergic receptor blockade and preventing conversion of T4 to T3 in periphery), change systemic decompensation, care about precipitating factors or intercurrent diseases and definitive treatment. TS treatment has a specific algorithm aiming to different manifestations and body systems.
28
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