INTERNAL MEDICINE / HOSPITAL MEDICINE BOARD REVIEW MANUAL STATEMENT OF EDITORIAL PURPOSE Myxedema Coma The Internal Medicine/Hospital Medicine Board and Thyroid Storm: Review Manual is a study guide for trainees and practicing physicians preparing for board examinations in internal medicine and hos- Diagnosis and Management pital medicine. Each manual reviews a topic essential to the current practice of internal Contributors: medicine and hospital medicine. Maybelline V. Lezama, MD Assistant Professor of Medicine, Texas A&M Health Science Center College of Medicine, Temple, TX Nnenna E. Oluigbo, MD PUBLISHING STAFF Saint Mary’s Hospital, New Haven, CT Jason R. Ouellette, MD PRESIDENT, GROUP PUBLISHER Vice Chairman, Residency Program Director, Bruce M. White Department of Medicine, Saint Mary’s Hospital; Assistant Clinical Professor, Yale University School of SENIOR EDITOR Medicine, New Haven, CT Robert Litchkofski EXECUTIVE VICE PRESIDENT Barbara T. White EXECUTIVE DIRECTOR OF OPERATIONS Jean M. Gaul Table of Contents Introduction . 2 Myxedema Coma . 2 Thyroid Storm. .6 NOTE FROM THE PUBLISHER: Summary Points. 11 This publication has been developed with- out involvement of or review by the Amer- References . 11 ican Board of Internal Medicine. www.turner-white.com Internal Medicine / Hospital Medicine Volume 14, Part 2 1 Myxedema Coma and Thyroid Storm InternAl Medicine/HospitAl Medicine BOArd RevieW MANUAL Myxedema Coma and Thyroid Storm: Diagnosis and Management Maybelline V. Lezama, MD, Nnenna E. Oluigbo, MD, and Jason R. Ouellette, MD INTRODUCTION but arousable. Vital signs include: oral temperature, 95°F; heart rate, 52 bpm; blood pressure, 110/50 Thyroid storm and myxedema coma are dis- mm Hg; respiratory rate, 15 breaths/min; and oxy- orders that fall within the spectrum of endocrine gen saturation, 92% on 4 L of oxygen. The physical emergencies. Considered true medical emergen- examination in the emergency department is unre- cies, these entities should be suspected in patients markable. Notable laboratory values include: white with extreme manifestations of hypothyroidism or blood cell count (WBC), 12,000 cells/µL; sodium, 128 hyperthyroidism. Although they have a low inci- mEq/L; potassium, 5 mEq/L; blood urea nitrogen, dence, they must be promptly recognized and ade- 8 mg/dL; and creatinine, 1.5 mg/dL. The arterial quately treated in order to reduce associated mor- blood gas reveals acute respiratory acidosis with pH bidity and mortality. Aggressive treatment should of 7.23; PaCO2 of 63.7 mm Hg; and PaO2 of 71.2 be initiated in the medical intensive care unit and mm Hg on room air. Chest radiograph and head should not be delayed until the results of thyroid computed tomography are unremarkable. Diagno- function tests are available. With prompt recogni- sis of hypercapnic respiratory failure is made, and tion, morbidity and mortality related to myxedema the patient is admitted to the medical intensive care coma and thyroid storm may be diminished. unit. The patient becomes more lethargic and her respiratory acidosis worsens, requiring mechanical ventilation. A more exhaustive examination reveals MYXEDEMA COMA generalized puffiness, periorbital edema, ptosis, and macroglossia, and her extremities are dry and cool with nonpitting edema. Myxedema coma is highly CASE PRESENTATION suspected, and the patient is started on intravenous A 65-year-old woman with no known past medical levothyroxine. Her thyroxine (T4) level is below 0.35 history is brought to the emergency department with ng/dL and her thyroid-stimulating hormone level is altered mental status. On arrival, the patient is drowsy above 200 µIU/mL. 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Turner White Communications accepts no responsibility for statements made by authors and will not be liable for any errors of omission or inaccuracies. Information contained within this publication should not be used as a substitute for clinical judgment. 2 Hospital Physician Board Review Manual www.turner-white.com Myxedema Coma and Thyroid Storm Table 1. Common Precipitating Factors of Myxedema Coma Mortality had once been estimated to range from 3 Stroke 50% to 60%. However, a high level of clinical sus- Congestive heart failure picion with earlier recognition, as well as advances Surgery in intensive care and overall management, have de- Trauma creased mortality to approximately 20% to 25%.4 Gastrointestinal bleeding Infections Drugs ETIOLOGY Anesthetics Myxedema most commonly develops in patients Amiodarone with neglected, inadequately treated, or undiag- Lithium Sedatives nosed hypothyroidism. Multiple factors appear to Metabolic disturbances precipitate myxedema coma, including the follow- Hypoglycemia ing: gastrointestinal bleeding; infection; metabolic Hypoxemia disturbances such as acidosis, hypoxemia, and Acidosis hypercapnia; stroke; and cardiovascular compro- Hypercapnia mise (Table 1).5 Many patients who develop myxedema coma are initially hospitalized with an unrelated medical OVERVIEW condition. During hospitalization, the patient slowly Myxedema coma is an extreme manifestation of develops a change in mental status. The diagno- hypothyroidism. It presents as central nervous sys- sis may not be suspected initially, especially when tem dysfunction, defective thermoregulation, and narcotics or sedatives are being used.3 cardiopulmonary decompensation. While most Drugs such as amiodarone and lithium are believe that patients must be comatose for myx- also reported as precipitants of myxedema coma, edema coma to be considered, deterioration in the especially in patients with a history of lithium- or patient’s mental status in the appropriate clinical amiodarone-induced hypothyroidism. This is due setting is enough to consider this entity.1 in part to the effects of these drugs on thyroid hormone metabolism.6,7 Lithium increases intra- EPIDEMIOLOGY thyroidal iodine content, inhibits the coupling of Myxedema coma was first reported by Ord in iodotyrosine residues to form T4 and triiodothyro- 8 1879 in London. It is a rare disorder, with only ap- nine (T3), and inhibits their secretion. Amiodarone proximately 300 cases described in the literature. has a high iodine content, and hypothyroidism can Patients are typically elderly females and often occur due to the antithyroid effects of iodine. It have longstanding, undiagnosed hypothyroidism.2 also has an effect on thyroid hormone synthesis More than 90% of cases occur during winter and release, especially in patients with underlying months, suggesting that low temperatures are a thyroid disease.6 potential contributing factor. Age-related loss of temperature regulation, in addition to a decrease in CLINICAL PRESENTATIONS heat production secondary to hypothyroidism, may The diagnosis of myxedema coma is a clinical also contribute.1 one, and virtually every organ system can be af- www.turner-white.com Internal Medicine / Hospital Medicine Volume 14, Part 2 3 Myxedema Coma and Thyroid Storm fected. Patients often present with symptoms of Respiratory dysfunction may also lead to obstruc- hypothyroidism, including excessive fatigue, weight tive sleep apnea,17 and this may be associated with gain (despite a decrease in appetite), constipation, weight gain and obesity. and cold intolerance. Atypical presentations can occur in elderly patients, who may simply exhibit Cardiovascular decreased mobility.9 Cardiovascular manifestations include bradycar- dia and low cardiac output due to decreased car- Central Nervous System diac contractility; however, frank congestive heart Altered mental status may range from mild confu- failure is rare.3 Narrow pulse pressure and diastolic sion, apathy, and lethargy to obtundation and coma. hypertension is often seen in the early stages. Hy- While all patients with myxedema coma present with potension may be seen in the later stages, and it is some degree of altered mental status, only a few frequently exacerbated by bradycardia, low cardiac present with true coma.10 Cognitive impairment (eg, output, and decreased blood volume. Increased decreased attention, motor speed, memory, and systemic peripheral resistance occurs and is thought visual/spatial organization) and psychiatric disorders to be due to decreased T3 levels. Pericardial effu- (eg, depression, dementia) are other manifestations. sions may occur as a result of increased capillary The mechanism for this change in mental status is permeability, leading to fluid accumulation. Cardiac largely unknown; however, it has been reported that tamponade, however, is rare.16 there is decreased cerebral blood flow and cerebral glucose