Thyroid Storm

Endocrine System


Clinicals - History

Fact Explanation

Introduction


Thyroid storm, also known as a thyrotoxic crisis, is a medical emergency that occurs in people with hyperthyroidism. It can lead to acute multisystem failure and death.

Precipitating factors


Patients often have a recent history of infection. Other precipitating factors include diabetic complications, pulmonary embolism, surgery, trauma, childbirth, and other causes of physiological stress. These events can lead to freeing of bound thyroid hormones and increased sensitivity of their receptors. The use of radioactive iodine can lead to a massive release of thyroid hormones from the thyroid follicles. Finally, the untimely withdrawal of antithyroid medications can lead to rebound thyrotoxicosis.

Constitutional symptoms


Thyroid hormones play a role in every organ system. Patients with thyroid storm can present with constitutional symptoms such as weakness and fatigue. Circulating thyroid hormones can enter the cellular cytoplasm where T4 is converted to T3, its active form. Then, T3 binds to nuclear thyroid receptors that induce a cell-specific change in gene activation and protein transcription. The constitutional symptoms and are due to adrenergic hyperactivity and exaggerated excitability of the muscles and central nervous system (CNS).

Neuropsychiatric symptoms


Patients may present with a wide range of neuropsychiatric symptoms. These include anxiety, hyperirritability, emotional lability, confusion, apathy, and coma. Rarely, dramatic psychotic symptoms, such as delusional parasitosis, can occur. The pathophysiology of neuropsychiatric manifestations of thyroid disease is complex, however, thyroid hormones are known to influence neurotransmitter release and hormone activation.

Palpitations


Cardiac palpitations are common in patients with thyroid storm. The thyroid hormone directly increases heart and ventricle contractility and thyroid storm can lead to adrenergic hyperactivity.

Diarrhea


Diarrhea can occur in thyrotoxicosis due to increased motility, malabsorption, and increased adrenergic activity.

Introduction


Thyroid storm, also known as a thyrotoxic crisis, is a medical emergency that occurs in people with hyperthyroidism. It can lead to acute multisystem failure and death.

Precipitating factors


Patients often have a recent history of infection. Other precipitating factors include diabetic complications, pulmonary embolism, surgery, trauma, childbirth, and other causes of physiological stress. These events can lead to freeing of bound thyroid hormones and increased sensitivity of their receptors. The use of radioactive iodine can lead to a massive release of thyroid hormones from the thyroid follicles. Finally, the untimely withdrawal of antithyroid medications can lead to rebound thyrotoxicosis.

Constitutional symptoms


Thyroid hormones play a role in every organ system. Patients with thyroid storm can present with constitutional symptoms such as weakness and fatigue. Circulating thyroid hormones can enter the cellular cytoplasm where T4 is converted to T3, its active form. Then, T3 binds to nuclear thyroid receptors that induce a cell-specific change in gene activation and protein transcription. The constitutional symptoms and are due to adrenergic hyperactivity and exaggerated excitability of the muscles and central nervous system (CNS).

Neuropsychiatric symptoms


Patients may present with a wide range of neuropsychiatric symptoms. These include anxiety, hyperirritability, emotional lability, confusion, apathy, and coma. Rarely, dramatic psychotic symptoms, such as delusional parasitosis, can occur. The pathophysiology of neuropsychiatric manifestations of thyroid disease is complex, however, thyroid hormones are known to influence neurotransmitter release and hormone activation.

Palpitations


Cardiac palpitations are common in patients with thyroid storm. The thyroid hormone directly increases heart and ventricle contractility and thyroid storm can lead to adrenergic hyperactivity.

Diarrhea


Diarrhea can occur in thyrotoxicosis due to increased motility, malabsorption, and increased adrenergic activity.

Clinicals - Examination

Fact Explanation

Altered vital signs


Thyroid storm can result in altered vital signs, such as fever, tachycardia, hypertension, and dyspnea. This is because the thyroid hormones have ionotropic and chronotropic effects that lead to increased blood volume, heart rate, contractility, and output. Fever is the result of a hypermetabolic state that leads to increased use of metabolic fuels, oxygen consumption, and increased sympathetic activity.

Neurologic findings


Patients with thyroid storm can present with varied neurologic findings. Altered mental status can present as hyperirritability, anxiety, confusion, psychosis, seizures, and coma due to the effect on neurotransmitters and hormone activation.

Tremor


Patients with thyrotoxicosis can present with tremor due to increased adrenergic activity.

Ophthalmopathy


Ophthalmoplegia, lid lag, stare, and exophthalmos can occur with patients with thyroid storm and underlying Graves' disease. This is due to an inflammatory process rather than the effect of the thyroid hormone.

Pericardial rub


Rarely, pericardial rub can be heard if a pericardial effusion occurs.

Excessive sweating


Patients with thyroid storm can present with warm skin with excessive sweating. This is due to increased sympathetic and adrenal action.

High-output heart failure


Thyroid storm can lead to high-output heart failure due to increased cardiac sensitivity to catecholamines and hemodynamic changes that lead to decreased contractility. This can result in peripheral edema or pulmonary congestion.

Altered vital signs


Thyroid storm can result in altered vital signs, such as fever, tachycardia, hypertension, and dyspnea. This is because the thyroid hormones have ionotropic and chronotropic effects that lead to increased blood volume, heart rate, contractility, and output. Fever is the result of a hypermetabolic state that leads to increased use of metabolic fuels, oxygen consumption, and increased sympathetic activity.

Neurologic findings


Patients with thyroid storm can present with varied neurologic findings. Altered mental status can present as hyperirritability, anxiety, confusion, psychosis, seizures, and coma due to the effect on neurotransmitters and hormone activation.

Tremor


Patients with thyrotoxicosis can present with tremor due to increased adrenergic activity.

Ophthalmopathy


Ophthalmoplegia, lid lag, stare, and exophthalmos can occur with patients with thyroid storm and underlying Graves' disease. This is due to an inflammatory process rather than the effect of the thyroid hormone.

Pericardial rub


Rarely, pericardial rub can be heard if a pericardial effusion occurs.

Excessive sweating


Patients with thyroid storm can present with warm skin with excessive sweating. This is due to increased sympathetic and adrenal action.

High-output heart failure


Thyroid storm can lead to high-output heart failure due to increased cardiac sensitivity to catecholamines and hemodynamic changes that lead to decreased contractility. This can result in peripheral edema or pulmonary congestion.

Differential Diagnoses

Fact Explanation

Pheochromocytoma


Pheochromocytoma can present with palpitations, diaphoresis, hypertension, anxiety, weakness, and weight loss. However, flushing, dyspnea, and blurred vision are more likely in pheochromocytoma and these patients will present increased metanephrine levels in urine and plasma.

Anxiety disorder


Generalized anxiety disorder (GAD), panic attack, and other anxiety disorders can lead to palpitations, tachycardia, nausea, and severe anxiety. Dizziness, dyspnea, tingling and numbness of the hands is more likely in anxiety disorder.

Cardiac arrhythmia


Cardiac arrhythmia can present with palpitations, tachycardia, and anxiety. However, patients with arrhythmia can have lightheadedness, dizziness, reduced exercise tolerance or may be asymptomatic. Note that thyroid storm leads to tachycardia and atrial fibrillation in some patients.

Sepsis


Sepsis can lead to fever, tachycardia, and altered mental status. However, hypothermia, tachypnea, multiple organ dysfunction syndrome (MODS), the presence of infectious foci, and lactic acidosis are more suggestive of sepsis.

Neuroleptic malignant syndrome


Neuroleptic malignant syndrome (NMS) can lead to fever, irritability, altered mental status, tachycardia, blood pressure lability, tachypnea, diaphoresis, hyperreflexia, tremor, and seizures. Muscle rigidity, sialorrhea, chorea, akinesia, trismus, opisthotonos, blepharospasm, oculogyric crisis, and dysphagia are more suggestive of NMS. Also, a history of antipsychotic use may be present.

Serotonin syndrome


Patients with serotonin syndrome may also present with hypertension, hyperthermia, irritability, tachycardia, diaphoresis, tremor, hyperreflexia, delirium, and coma. However, mydriasis, myoclonus, horizontal ocular clonus, and rigidity are more likely in serotonin syndrome. Also, these patients often have a history of using any drug that increases the effect of serotonin on the CNS.

Pheochromocytoma


Pheochromocytoma can present with palpitations, diaphoresis, hypertension, anxiety, weakness, and weight loss. However, flushing, dyspnea, and blurred vision are more likely in pheochromocytoma and these patients will present increased metanephrine levels in urine and plasma.

Anxiety disorder


Generalized anxiety disorder (GAD), panic attack, and other anxiety disorders can lead to palpitations, tachycardia, nausea, and severe anxiety. Dizziness, dyspnea, tingling and numbness of the hands is more likely in anxiety disorder.

Cardiac arrhythmia


Cardiac arrhythmia can present with palpitations, tachycardia, and anxiety. However, patients with arrhythmia can have lightheadedness, dizziness, reduced exercise tolerance or may be asymptomatic. Note that thyroid storm leads to tachycardia and atrial fibrillation in some patients.

Sepsis


Sepsis can lead to fever, tachycardia, and altered mental status. However, hypothermia, tachypnea, multiple organ dysfunction syndrome (MODS), the presence of infectious foci, and lactic acidosis are more suggestive of sepsis.

Neuroleptic malignant syndrome


Neuroleptic malignant syndrome (NMS) can lead to fever, irritability, altered mental status, tachycardia, blood pressure lability, tachypnea, diaphoresis, hyperreflexia, tremor, and seizures. Muscle rigidity, sialorrhea, chorea, akinesia, trismus, opisthotonos, blepharospasm, oculogyric crisis, and dysphagia are more suggestive of NMS. Also, a history of antipsychotic use may be present.

Serotonin syndrome


Patients with serotonin syndrome may also present with hypertension, hyperthermia, irritability, tachycardia, diaphoresis, tremor, hyperreflexia, delirium, and coma. However, mydriasis, myoclonus, horizontal ocular clonus, and rigidity are more likely in serotonin syndrome. Also, these patients often have a history of using any drug that increases the effect of serotonin on the CNS.

Investigations - Diagnosis

Fact Explanation

Diagnostic criteria


Serum levels of free thyroid hormones, T3 and T4 are elevated in thyroid storm.

Serum thyroid hormones


TSH levels should be measured in patients with hyperthyroidism to help distinguish between primary and secondary causes of hyperthyroidism.

Serum TSH levels


The formation of TSH receptor antibodies (TRAb) leads to Graves' disease, the most common cause of hyperthyroidism.

TSH receptor antibodies


A radioactive iodine uptake test (RAIU) can be useful for determining the etiology of hyperthyroidism.

Diagnostic criteria


The diagnostic criteria for thyroid storm include elevated thyroid hormones, CNS manifestations, fever, tachycardia about 130 bpm, congestive heart failure, GI symptoms, and liver injury. Thyrotoxicosis is a prerequisite for diagnosis.

Thyroid ultrasound


A thyroid ultrasound can be used to evaluate the size, vascularity, and the presence of nodules. This can be useful to determine thyroid pathology.

Diagnostic criteria


Serum levels of free thyroid hormones, T3 and T4 are elevated in thyroid storm.

Serum thyroid hormones


TSH levels should be measured in patients with hyperthyroidism to help distinguish between primary and secondary causes of hyperthyroidism.

Serum TSH levels


The formation of TSH receptor antibodies (TRAb) leads to Graves' disease, the most common cause of hyperthyroidism.

TSH receptor antibodies


A radioactive iodine uptake test (RAIU) can be useful for determining the etiology of hyperthyroidism.

Diagnostic criteria


The diagnostic criteria for thyroid storm include elevated thyroid hormones, CNS manifestations, fever, tachycardia about 130 bpm, congestive heart failure, GI symptoms, and liver injury. Thyrotoxicosis is a prerequisite for diagnosis.

Thyroid ultrasound


A thyroid ultrasound can be used to evaluate the size, vascularity, and the presence of nodules. This can be useful to determine thyroid pathology.

Investigations - Management

Fact Explanation

Electrocardiogram


An electrocardiogram should be performed due to the frequency of cardiac arrhythmia, particularly in older patients with structural heart disease.

Liver function tests


Liver enzymes may be elevated due to increased metabolism in patients with thyrotoxicosis.

Electrolytes


Electrolytes can help identify comorbid conditions and hypercalcemia that can result due to increased bone resorption and hemoconcentration.

Electrocardiogram


An electrocardiogram should be performed due to the frequency of cardiac arrhythmia, particularly in older patients with structural heart disease.

Liver function tests


Liver enzymes may be elevated due to increased metabolism in patients with thyrotoxicosis.

Electrolytes


Electrolytes can help identify comorbid conditions and hypercalcemia that can result due to increased bone resorption and hemoconcentration.

Management - Supportive

Fact Explanation

Supportive care


Normal saline can be to replace fluid losses from fever, sweating, and diarrhea. Dextrose-containing fluids are used if hypoglycemia is present. Aggressive cooling strategies, including acetaminophen use, cooling blankets, and ice packs should be performed in patients with high fever.

Treatment of precipitating events


Treatment of thyroid storm includes identifying and managing any precipitating factors.

ICU admission


Admission to the ICU is recommended for all patients with thyroid storm, especially those with disseminated intravascular coagulopathy (DIC), shock, multiple organ failure, and patients with APACHE scores >9. This is because of high mortality rate of patients with thyroid storm and organ failure.

Supportive care


Normal saline can be to replace fluid losses from fever, sweating, and diarrhea. Dextrose-containing fluids are used if hypoglycemia is present. Aggressive cooling strategies, including acetaminophen use, cooling blankets, and ice packs should be performed in patients with high fever.

Treatment of precipitating events


Treatment of thyroid storm includes identifying and managing any precipitating factors.

ICU admission


Admission to the ICU is recommended for all patients with thyroid storm, especially those with disseminated intravascular coagulopathy (DIC), shock, multiple organ failure, and patients with APACHE scores >9. This is because of high mortality rate of patients with thyroid storm and organ failure.

Management - Specific

Fact Explanation

Thionamides


Thionamides are a class of antithyroid drugs that include methimazole and propylthiouracil (PTU). They decrease the synthesis of thyroid hormones through the inhibition of thyroid peroxidase (TPO). PTU should be avoided during the second and third trimesters of pregnancy.

Iodine


Iodine therapy should be initiated one hour after the administration of thioamides. This prevents the release of thyroid hormones from follicular cells. Iodine-induced hyperthyroidism, amiodarone-induced thyrotoxicosis, and iodine hypersensitivity are contraindications.

Lithium


Lithium can be used in patients with a contradiction to iodine therapy. It acts by inhibiting the synthesis and release of thyroid hormone.

Propanolol


Beta-blockade should be provided to counter the adrenergic effects of thyroid storm. Propanolol is the beta-blocker of choice but use caution in patients with heart failure and consider using esmolol, a short-acting beta-blocker. Contraindications include asthma and chronic obstructive pulmonary disease (COPD).

Glucocorticoids


Glucocorticoids, such as dexamethasone and hydrocortisone, improves survival rates in patients with thyroid storm. They are powerful inhibitors of the conversion of T4 to T3.

Definitive treatment


Once euthyroidism has been achieved, thyroidectomy or radioactive iodine treatment can be used to prevent further flare-ups.

Thionamides


Thionamides are a class of antithyroid drugs that include methimazole and propylthiouracil (PTU). They decrease the synthesis of thyroid hormones through the inhibition of thyroid peroxidase (TPO). PTU should be avoided during the second and third trimesters of pregnancy.

Iodine


Iodine therapy should be initiated one hour after the administration of thioamides. This prevents the release of thyroid hormones from follicular cells. Iodine-induced hyperthyroidism, amiodarone-induced thyrotoxicosis, and iodine hypersensitivity are contraindications.

Lithium


Lithium can be used in patients with a contradiction to iodine therapy. It acts by inhibiting the synthesis and release of thyroid hormone.

Propanolol


Beta-blockade should be provided to counter the adrenergic effects of thyroid storm. Propanolol is the beta-blocker of choice but use caution in patients with heart failure and consider using esmolol, a short-acting beta-blocker. Contraindications include asthma and chronic obstructive pulmonary disease (COPD).

Glucocorticoids


Glucocorticoids, such as dexamethasone and hydrocortisone, improves survival rates in patients with thyroid storm. They are powerful inhibitors of the conversion of T4 to T3.

Definitive treatment


Once euthyroidism has been achieved, thyroidectomy or radioactive iodine treatment can be used to prevent further flare-ups.

References

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