Part 1: Hyperthyroidism and Thyroid Storm

By Joseph J. Mistovich, MEd, NREMT-P, William S. Krost, BSAS, EMT-P , & Daniel Limmer, AS, EMT-P 

This article is the first in a two-part series addressing endocrine emergencies involving thyroid hormone disorders. The second part will follow in next month's issue and cover conditions related to hypothyroidism. The section below on anatomy and physiology of the thyroid gland pertains to both articles. It will be important to review this section prior to reading the next article to completely understand the hypothyroidism conditions covered in part two.

The endocrine emergencies most commonly discussed by EMS providers typically deal with diabetes mellitus, a condition associated with malfunction of the pancreas or its hormones and improper regulation of the blood glucose level. It is important to recognize that there are many other emergencies that may be related to malfunctioning endocrine glands or hormones. These emergencies may produce acute life-threatening conditions that exhibit a wide variety of clinical presentations based on the gland or hormones involved. Some patients may not readily recognize, or may ignore, the slow and progressive clinical changes that are occurring and allow the disease to create an acute life-threatening condition.

     Since EMS providers may be called upon to manage the patient experiencing this acute and potentially life-threatening condition, it is prudent for them to possess an awareness and understanding of other potential life-threatening endocrine emergencies, such as those involving the thyroid gland and its related hormones.

Anatomy and Physiology of The Thyroid Gland
     The thyroid is a butterfly-shaped endocrine gland located in the anterior neck just inferior to the thyroid cartilage (Adam's apple). It consists of two lateral lobes that are connected anteriorly by a mass of tissue referred to as the isthmus. It can be easily palpated just below the cricoid cartilage. The size of the gland varies in individuals depending on many factors. The thyroid gland is the largest pure endocrine gland in the body and has a very rich blood supply. Thus, when performing a needle cricothyrotomy, it is extremely important to ensure that the proper landmarks have been identified to avoid inadvertent laceration of the vascular lateral lobes or isthmus of the thyroid gland. If these are lacerated, an excessive amount of bleeding may occur, complicating an already dire airway situation. The gland may also be lacerated and bleed heavily from blunt or penetrating trauma to the anterior neck.

     The thyroid gland produces and secretes two distinct hormones: thyroid hormone (TH) and calcitonin. Calcitonin is produced by a different group of cells within the thyroid gland, and is responsible for lowering the blood levels of calcium and stimulation of bone growth and development in childhood. It may also play a role in reducing bone loss associated with starvation and in late stages of pregnancy when the fetus is competing for calcium being absorbed in the digestive tract. Otherwise, the role of calcitonin in the healthy adult is not well understood; it may serve merely as a weak hypocalcemic agent.

     The thyroid hormone is comprised of two different iodide-attached molecules. Thyroxine, also known as tetraiodothyronine or T4, makes up the majority of hormone secreted by the thyroid cells. It consists of four iodide ions attached to its molecular structure. Triiodothyronine, also known as T3, is the other hormone secreted by the thyroid gland. It has only three iodide ions attached to it. Although only a small amount of T3 is secreted by the thyroid gland, approximately 10% of the TH secretion, a large amount is formed from the conversion of T4 through the removal of one iodine group by enzymes from the liver, kidneys and other tissues. Interestingly, though, T3 is primarily responsible for the thyroid hormone effect, which is primarily a very strong, immediate and short-acting increase in cellular metabolism.

     It is important to review the transport, binding and concentration of T3 and T4 in the blood in order to understand a potential trigger for the disease process involving the thyroid hormone. Approximately 75% of T4 and 70% of T3 hormones attach to thyroid-binding globulins, also known as thyroxine-binding globulins (TBGs), upon entering the blood. A majority of the remaining T3 and T4 are attached to the plasma protein albumin or a thyroid-binding prealbumin. Very small amounts of the thyroid hormone, approximately 0.3% of T3 and 0.03% of T4, are left unbound to diffuse into the peripheral tissue. Thus, the only useable form of thyroid hormone is in an unbound form.

     Both T3 and T4 bind to target tissue receptors; however, T3 binds much more readily and is about 10 times more active than T4. Equilibrium must be maintained in the blood between the amount of thyroid hormones bound to protein carriers and the amount being released into the peripheral tissue. Levels of T4 and the thyroid-stimulating hormone (TSH) play a major role in maintaining this blood level equilibrium. It is interesting to note that more than a week's supply of thyroid hormone is found in the bloodstream.

     Thyroid hormones affect many of the major organ systems and tissues within the body, with the exception of only the adult brain, spleen, testes, uterus and thyroid gland itself. Effects of the thyroid hormones are to:

• Maintain normal sensitivity of respiratory centers to changes in oxygen and carbon dioxide concentrations
• Maintain normal cell oxygen use
• Maintain a normal basal metabolic rate (BMR)
• Promote calorigenesis (heat production) by increasing the metabolic rate of cells
• Enhance the effects of the sympathetic nervous system
• Promote glucose metabolism, fat mobilization and protein synthesis
• Maintain normal adult nervous system function
• Promote normal cardiac function to include rate and force of contraction
• Promote normal muscle development and function, and skeletal growth and maturation
• Promote normal gastrointestinal (GI) motility and tone, and increase digestive enzyme secretion
• Maintain hydration and secretory function of the skin.

     Hypothyroidism, an insufficient number of thyroid hormones, or hyperthyroidism, an excessive number of thyroid hormones, will cause metabolic disturbances that disrupt normal body function and have an impact on most or all of the aforementioned hormone effects. Hypothyroidism results in a decrease in hormonal effects on the body systems; hyperthyroidism increases or accentuates the thyroid hormone effects on body systems. Both conditions can lead to acute and potentially lethal emergencies.

Pathophysiology
     Hyperthyroidism describes a condition of excessive secretion of thyroid hormone resulting from elevated and inappropriate thyroid function. Thyrotoxicosis, also associated with an excessive amount of circulating thyroid hormone, results from the patient taking too much thyroid hormone (an exogenous source), or from an inflamed thyroid gland releasing too much stored thyroid hormone. Although these terms are often used interchangeably to describe an elevated thyroid hormone level, they have different etiologies that affect long-term treatment. Hyperthyroidism and thyrotoxicosis typically describe the milder form of the disease process.

     Graves' disease, also known as diffuse toxic goiter, is the most common form of hyperthyroidism. It is typically more common in women and usually occurs between the ages of 20 and 40. Graves' results from an autoimmune condition that affects the function of the thyroid-stimulating hormone, causing the thyroid gland to increase its production and secretion of thyroid hormone and leading to hyperthyroidism.

     Thyroid storm, also referred to as thyrotoxic crisis, represents a severe and potentially life-threatening condition. Although it is a relatively rare condition, occurring in only 1% to 2% of patients with hyperthyroidism, if left untreated, thyroid storm can be fatal, sometimes within days. It carries an adult mortality rate of 10%-20%. The pathophysiology of thyroid storm is not completely understood; however, it is thought that the excessive levels of thyroid hormone are not necessarily from the thyroid gland but from the conversion of bound-thyroid hormone in the blood to an unbound form. The unbound form becomes active and can easily enter peripheral tissue, producing a dangerous and possibly life-threatening hypermetabolic state and increased sympathetic nervous system activity. The patient may present with an excessively high fever (106°F), tachycardia, nausea, vomiting, diarrhea and hypotension.

     Graves' disease is the most common underlying cause of thyroid storm. Other causes include taking an excessive amount of thyroid hormone (factitious hyperthyroidism) and administration of amiodarone, a rich iodine-containing antidysrhythmic agent that can have complex effects on the thyroid gland and hormone function. Other conditions that may precipitate thyroid storm in the patient with hyperthyroidism include: infection, surgery, burns, trauma, cardiovascular events, preeclampsia or eclampsia, diabetic ketoacidosis, hyperglycemic hyperosmolar nonketotic syndrome, insulin-induced hypoglycemia, pulmonary embolism, ingestion of thyroid hormone and drug reactions (Mellaril, Itrumil).

Assessment
     It is important to understand the history and physical exam findings in a patient with hyperthyroidism. A patient who presents with life-threatening thyroid storm may have an undiagnosed history of hyperthyroidism. Although hyperthyroidism and thyroid storm may present with a wide clinical array of signs and symptoms, clinical features of a hypermetabolic state and increased sympathetic activity are the most common. Key findings include agitation, weight loss, nervousness and palpitations. History findings include:

• Weight loss of approximately 15% of prior weight (often greater than 40 pounds)
• Cardiac palpitations
• Nervousness
• Anxiety, agitation, restlessness
• Wide mood swings
• Tremors
• Chest pain in the absence of cardiovascular disease
• Dyspnea
• Edema
• Disorientation
• Psychosis
• Weakness
• Diarrhea and increased bowel movements
• Increased perspiration
• Fatigue
• Intolerance to heat from the hypermetabolic state
• Abdominal pain.

Physical exam findings include:

• Fever (excessively high in thyroid storm)
• Tachycardia (often 100-170 bpm) that is out of proportion to the fever
• Wide pulse pressure (40-100 mmHg) due to the increase in cardiac contractility (inotrope) with an elevation in systolic blood pressure
• Warm skin
• Diaphoresis
• Dehydration (may be secondary to diaphoresis and diarrhea)
• Congestive heart failure
• Thyromegaly (enlarged thyroid gland)
• Exopthalmos (protruded eyeballs)
• Stare with eyelid retraction
• Atrial fibrillation, atrial flutter, or premature atrial contractions
• Tremors
• Tender liver
• Shock
• Jaundice
• Coma or obtunded mental state.

     The enlarged thyroid gland in Graves' is typically diffuse and nontender to palpation. If there is infection or inflammation, the gland will present with diffuse enlargement and pain on palpation.

     Exopthalmos occurs when the tissue behind the eyes becomes edematous and fibrous and the extraocular muscles degenerate. This is thought to result from the autoimmune disorder associated with hyperthyroidism. In some cases, the protrusion is so severe that the optic nerve is stretched and vision is impaired. Severe eyeball protrusion may cause the eyelids to stretch and not close completely when the patient blinks or sleeps. This may lead to drying and irritation of the outer eye tissue, causing corneal ulcerations.

     It is important for EMS providers to recognize not only the patient experiencing a thyroid storm, but also one who is exhibiting an array of signs and symptoms that are characteristic of hyperthyroidism. The hyperthyroid condition may progress rapidly to thyroid storm or congestive heart failure if not treated.

Management
     Thyroid storm is a life-threatening condition that requires immediate emergency care and transport. Severe hyperthyroidism may also require supportive emergency care. Consider the following when managing a patient with an acute and severe hyperthyroid condition:

• Establish and maintain a patent airway. If the patient presents with an altered mental status or is comatose, it may be necessary to establish an airway by a manual maneuver, and potentially with a mechanical device, including endotracheal intubation, in severely altered mental states.
• Establish and maintain an adequate ventilation status. If the patient's respiratory rate or tidal volume is inadequate, it is necessary to provide positive pressure ventilation.
• Establish and maintain adequate oxygenation. Assess the patient for evidence of hypoxia. Apply a pulse oximeter and determine the SpO₂ reading. If there is either clinical evidence of hypoxia or a SpO₂ reading of less than 95% on room air, administer a high concentration of oxygen via a non-rebreather mask. If the patient is exhibiting no signs of hypoxia or the SpO₂ reading is greater than 95%, supplemental oxygen may be applied via a nasal cannula at 2-4 lpm, especially if any dyspnea, chest pain or congestive heart failure is exhibited during the history or physical exam.
• Provide continuous ECG monitoring. Patients experiencing hyperthyroidism or thyroid storm may present with cardiac dysrhythmias. Atrial fibrillation is common, especially in the elderly. Patients may also experience atrial flutter and premature atrial contractions. Traditional management of the ventricular rate control in atrial fibrillation or conversion to a sinus rhythm may not be effective until the thyroid levels have been managed.
• Initiate an intravenous line of normal saline. Patients may lose significant amounts of fluid from excessive sweating and diarrhea. Aggressive fluid resuscitation may be necessary in severe cases.
• Initiate cooling measures if high fever is present. Remove the patient's clothing, mist the body with water and fan aggressively. If antipyretic therapy is considered, avoid the use of aspirin. Aspirin may decrease protein binding of thyroid hormones and increase the levels of unbound T3 and T4, thereby increasing the tissue uptake of thyroid hormone. Acetaminophen would be preferred over aspirin since it does not have this effect.
• Expeditious transport. If the patient is experiencing a thyroid storm or a severe hyperthyroid condition, consider rapid transport to an appropriate medical facility that can initiate definitive therapy to decrease the thyroid hormone levels.
• Consider medications. Blockading the peripheral adrenergic hyperactivity with beta blockers could be a critical factor in managing the thyroid storm patient. Propranolol (Inderal), the current beta blocker agent of choice, can reduce tachydysrhythmias, high body core temperature, tremors, restlessness, anxiety and palpitations. Another major indication for the specific use of propranolol is its ability to inhibit the conversion of T4 to T3 in the peripheral tissue. Keep in mind that T3 is responsible for the majority of thyroid hormone activity in the peripheral tissue. Contraindications to propranolol's use include reactive airway disease, atrioventricular blocks, bradydysrhythmias, cardiogenic shock, hypersensitivity to the drug and congestive heart failure. It is important to note that heart failure in hyperthyroidism and thyroid storm is typically a high-output CHF, or heart failure due to tachydysrhythmias that may respond well to the beta blocker therapy. However, use beta blockers with extreme caution if heart failure is suspected. The dose of propranolol is 1-2 mg intravenously, repeated every 10 to 15 minutes until the symptoms are controlled. Be sure to follow your local protocol in managing the thyroid storm patient. Another medication to consider is dexamethasone (Decadron), which also blocks the conversion of T4 to T3 in the peripheral tissue. Administer 2 mg intravenously. Again, it is important to follow local protocol when managing the patient.

Conclusion
     Even though the chance of responding to a patient experiencing a thyroid storm or thyrotoxic crisis is rare, be prepared to quickly identify the severity of the condition and initiate rapid supportive emergency care and transport. Possessing a fundamental understanding of the disease process will better prepare the EMS provider to rapidly recognize and manage this potentially acute life-threatening condition.

CEU Review Form Endocrine Emergencies Part 1 (PDF)Valid until December 3, 2007

Bibliography
Bledsoe BE, Porter RS, Cherry RA. Paramedic Care: Principles and Practice, Medical Emergencies, 2nd ed. Upper Saddle River, NJ: Prentice Hall Health, 2006.
Guyton AC, Hall JE. Textbook of Medical Physiology, 10th ed. Philadelphia: W.B. Saunders, 2001.
Marieb EN. Anatomy and Physiology, 2nd ed. San Francisco: Pearson Education, 2005.
Martini FH. Anatomy and Physiology. San Francisco: Pearson Education, 2005.
Marx JA, Hockberger RS, Walls RM. Rosen's Emergency Medicine: Concepts and Clinical Practice, 5th ed. St. Louis: Mosby, Inc., 2002.
Schraga ED. Hyperthyroidism, Thyroid Storm, and Graves Disease. www.emedicine.com/emerg/topic269.htm.

Joseph J. Mistovich, Med, NREMT-P, is a professor and chair of the Department of Health Professions at Youngstown (OH) State University, author of several EMS textbooks and a nationally recognized lecturer.

William S. Krost, BSAS, NREMT-P, is an operations manager and flight paramedic with the St. Vincent/Medical University of Ohio/St. Rita's Critical Care Transport Network (Life Flight) in Toledo, OH, and a nationally recognized lecturer.

Daniel D. Limmer, AS, EMT-P, is a paramedic with Kennebunk Fire-Rescue in Kennebunk, ME. He is the author of several EMS textbooks and a nationally recognized lecturer.

     This is the first part of a two-part series addressing endocrine emergencies involving the thyroid gland. Refer to Part Two in the November issue and online at http://www.emsresponder.com/