REVIEW ARTICLE Thyroid emergencies Dorina Ylli1, Joanna Klubo ‑Gwiezdzinska2, Leonard Wartofsky3,4 1 Endocrinology Division, University of Medicine, Tirana, Albania 2 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States 3 Endocrinology Division, Department of Medicine, Georgetown University School of Medicine, Washington DC, United States 4 MedStar Health Research Institute, MedStar Washington Hospital Center, Washington DC, United states KEY WORDS ABSTRACT coma, critical care, Myxedema coma and thyroid storm are among the most common endocrine emergencies presenting to hypothermia, general hospitals. Myxedema coma represents the most extreme, life ‑threatening expression of severe hypothyroidism, hypothyroidism, with patients showing deteriorating mental status, hypothermia, and multiple organ thyrotoxicosis system abnormalities. It typically appears in patients with preexisting hypothyroidism via a common pathway of respiratory decompensation with carbon dioxide narcosis leading to coma. Without early and appropriate therapy, the outcome is often fatal. The diagnosis is based on history and physical find‑ ings at presentation and not on any objective thyroid laboratory test. Clinically based scoring systems have been proposed to aid in the diagnosis. While it is a relatively rare syndrome, the typical patient is an elderly woman (thyroid hypofunction being much more common in women) who may or may not have a history of previously diagnosed or treated thyroid dysfunction. Thyrotoxic storm or thyroid crisis is also a rare condition, established on the basis of a clinical diagnosis. The diagnosis is based on the pres‑ ence of severe hyperthyroidism accompanied by elements of systemic decompensation. Considering that mortality is high without aggressive treatment, therapy must be initiated as early as possible in a critical care setting. The diagnosis cannot be established based on laboratory tests alone, but several scoring systems are available. The usual clinical signs and symptoms of hyperthyroidism are present along with more exaggerated clinical manifestations affecting the cardiovascular, gastrointestinal, and central nervous systems. A multipronged approach has been recommended and has been associated with improved outcomes. Introduction The entities myxedema coma and the abnormal thyroid state may continue, wors‑ thyroid storm represent the respective extremes en, or recur at a later time. of thyroid dysfunction. If not promptly and ap‑ propriately diagnosed and treated, both condi‑ Myxedema coma It should be appreciated that tions are associated with a poor outcome and myxedema coma is a clinical diagnosis as there high mortality. In approaching these as well as is no single test or group of laboratory investiga‑ Correspondence to: other endocrine emergencies, it is important to tions that establish the diagnosis in any defini‑ Prof. Leonard Wartofsky, MD, Georgetown University School of have a high index of suspicion for the diagnosis tive way. The most dramatic clinical finding is, of Medicine, Endocrinology Division, and to act counter to usual therapeutic approach‑ course, coma or precoma appearing in the setting Department of Medicine, MedStar es for most disorders by treating the suspected of hypothyroidism. The hypothyroidism may have Health Research Institute, MedStar condition before it is actually confirmed. This ‑ap been long ‑standing or previously undocumented, Washington Hospital Center, 110 Irving Street, N.W., Washington, proach proves valid because in these conditions and with the former, there is often a history of DC, USA 20 010-2975, email: the treatment indicated will rarely be harmful discontinuation of thyroid hormone replacement [email protected] in contrast to the risks inherent in not treating. medications. In the precomatose state, the typical Received: May 24, 2019. Accepted: May 24, 2019. Moreover, because myxedema coma and thyroid clinical findings include hypothermia, decreased Published online: August 29, 2019. storm typically occur in patients with preexistent mentation, generalized edema, and the usual hall‑ Pol Arch Intern Med. 2019; hypo‑ and hyperthyroidism, respectively, and are marks of profound hypothyroidism. A typical pre‑ 129 (7-8): 526-534 precipitated by some superimposed condition or sentation is a woman with the above findings, in doi:10.20452/pamw.14876 Copyright by Medycyna Praktyczna, nonthyroidal illness, it is important to identify the age range of 60 to 85 years, and presenting Kraków 2019 and address the precipitating event. Otherwise, in winter, when the temperatures are low, after 526 POLISH ARCHIVES OF INTERNAL MEDICINE 2019; 129 (7-8) TABLE 1 Factors known to precipitate myxedema coma that forms the basis for respiratory depression. In Hypothermia the presence of pneumonia, the downhill process is accelerated and torpor with slowed respiration Metabolic disruption Hypoglycemia coupled with airway obstruction from perilaryn‑ Hyponatremia geal edema and the large tongue lead to progres‑ Acidosis sive depression of the central nervous system and Hypercalcemia coma. The pathway to respiratory decompensa‑ Infections tion is further exacerbated by depressed function of respiratory musculature due to hypothyroid‑ Cerebrovascular accidents ism and the tendency for reduced lung volume Drugs Anesthetics due to fluid collections in the lung (pleural effu‑ Tranquilizers, sarbiturates, sedatives, Narcotics sion), heart (pericardial effusion), and abdomen Amiodarone, β ‑blockers, lithium (ascites). Ono et al2 analyzed 149 hospitalized pa‑ Discontinuation of thyroxine therapy tients with myxedema coma and noted that two‑ Burns ‑thirds were women and the group had an aver‑ age age of 77 years. Death was seen in 30% and Trauma with higher frequency in winter. Gastrointestinal bleeding Manifestations of myxedema coma like those Respiratory compromise Hypoxemia of thyroid storm reflect multisystem decompensa‑ Hypercapnia tion. Renal function is impaired due to decreased glomerular filtration, leading to symptomatic hy‑ ponatremia as the kidneys lose their ability to ex‑ being found down. Severely cold weather is only crete a free water load because of decreased deliv‑ one of the many possible precipitating factors ery of water to the distal nephron. Decreased car‑ that may convert the clinical status of the patient diac output and hypovolemia sensed by barore‑ from hypothyroidism to myxedema coma. Other ceptors may lead to a stimulation of antidiuretic possible precipitating events include hypoglyce‑ hormone release, further contributing to hypona‑ mia, hyponatremia, hypoxemia, and hypercapnia tremia and impaired free water excretion. The ef‑ (TABLE 1). In the overwhelming majority of patients, fects of such profound hypothyroidism on the gas‑ the basis for the underlying hypothyroidism is trointestinal tract include complaints of anorexia autoimmunity, that is, Hashimoto thyroiditis. and constipation. Reduced motility, gastric atony, The occurrence of secondary or central hypothy‑ paralytic ileus, and megacolon are not unusual. roidism due to thyrotropin deficiency related to It is highly important to consider underly‑ pituitary disease is much more rare. In the latter ing infection, for example, pneumonia, which is patients, it is critical to keep the possibility of as‑ a very common precipitant of myxedema coma. sociated hypoadrenalism in mind, which consti‑ This is because these patients may have the usu‑ tutes a justification for consideration of empiric al signs of infection masked by bradycardia and corticosteroid therapy. Medications that can pre‑ hypothermia, thus not demonstrating the fever cipitate myxedema coma include sedatives, anal‑ or tachycardia typical of infection. In one ret‑ gesics, antidepressants, hypnotics, antipsychot‑ rospective series, sepsis was highly correlated ics, and anesthetic drugs via a shared tendency with mortality, with 12 of the 23 patients (52%) to suppress respiration. Drug‑induced myxedema dying of sepsis.3 Findings in the cardiovascular coma is more common in patients not known to system include pericardial effusion, cardiomeg‑ have hypothyroidism and who are hospitalized aly, bradycardia, as well as reduced ejection frac‑ for other problems.1 tion and cardiac output due to decreased cardiac contractility. Findings on electrocardiography in‑ Clinical presentation If the patient is conscious clude bradycardia, various degrees of heart block, and communicative, his or her slow speech and and low voltage. Although bradycardia is almost hoarse voice may be the clue to hypothyroidism. always present, occasional patients may pres‑ A history of radioiodine therapy for nodular or ent with torsades de pointes ventricular tachy‑ diffuse toxic goiter may be elicited, or of having cardia.4 As implied above, the most dramatic as‑ discontinued taking thyroid hormone medication pect of the presentation is the coma per se, which prescribed previously. Rarely, laconic and clever typically evolves from initial lethargy, then pro‑ or sarcastic responses to questioning have been gressing to increased sleeping throughout the day, noted in the precomatose state and have been la‑ and then inability of family members to awaken belled as “myxedema wit.” On physical examina‑ the patient. Seizure can occur, doubtless facilitat‑ tion, there is dry and scaly skin, nonpitting ede‑ ed by the metabolic abnormalities. ma of the face, hands, and feet, macroglossia, delayed