Epidemiology, Etiology, And Pathophysiology
The occurrence of thyroid storm or myxedema coma is rare. The National Health and Nutrition Survey III reported the incidence of subclinical and clinical hyperthyroidism to be approximately 1%, with a roughly equal distribution between the two. Hypothyroidism is more prevalent, with a reported incidence of approximately 1% to 2% overall.4 Although overt hypothyroidism may be present in less than 0.5% of the population, the incidence of subclinical hypothyroidism is more prevalent and may affect up to 10% of elderly women.4-6 Both hyper- and hypothyroidism are more common in women.
The incidence of thyroid storm and myxedema coma is unknown. However, mortality rates forboth are exceedingly high. Untreated thyroid storm is fatal, and even with treatment, mortality ranges from 20% to 50%.7 Myxedema coma mortality rates as high as 80% have historically been reported, but even with current treatments, mortality rates remain at 30% to 60%.8,9 Eighty percent of myxedema coma patients are women, and most of these women are older than 60 years.10
Definitions And Etiology
Hyperthyroidism and hypothyroidism represent a clinical spectrum of disease. The terms hyperthyroidism and hypothyroidism in the strictest sense refer to hyperfunction and hypofunction of the thyroid gland, respectively. These conditions exist in a full spectrum ranging from clinically controlled disease to grossly decompensated, life-threatening conditions.
Thyrotoxicosis refers to any state characterized by a clinical excess of thyroid hormone. Thyroid storm represents the most extreme presentation of thyrotoxicosis. Both may be life threatening. Clinical judgment on the part of the emergency clinician determines which patients with thyrotoxicosis require intensive intervention and which are less acutely ill.
Myxedema coma is used to describe the severe life-threatening manifestations of hypothyroidism. The term myxedema coma itself is a misnomer, as patients do not usually present with frank coma but more commonly have altered mental status or mental slowing. Myxedema actually refers to the nonpitting puffy appearance of the skin and soft tissues related to hypothyroidism.
Decompensation of chronic thyroid disorders leads to myxedema and thyroid storm. Patients may have had a known history of a thyroid disorder and their conditions may have been well controlled, or patients may have had subclinical cases with no prior diagnosis. Factors precipitating thyroid decompensation include cold weather, infection, medication nonadherence, acute congestive heart failure, myocardial infarction, stroke, new medications, intoxication, and thyroid ablation. Infection is the most common precipitant of thyroid storm.11 Myxedema coma can be triggered by cold weather, with more than 90% of cases occurring during winter months.10
Thyroid hormone production is closely regulated via a negative feedback loop through the hypothalamicpituitary- thyroid axis. Thyroid hormone production begins with the oxidation of trapped serum iodide within the follicular cell membrane. This intermediate compound reacts with specific tyrosine residues to form the compounds monoiodotyrosine and diiodotyrosine. Various combinations of these molecules form triiodothyronine (T3) and thyroxine (T4). Release of the formed T4 and T3 are regulated by thyroid-stimulating hormone (TSH). Roughly 80% of the formed thyroid hormone within the thyroid is T4.12 In the bloodstream, T4 is more than 99% protein bound; that is, 1% is free in the circulation. Free T4 (FT4) is responsible for the negative feedback inhibition affecting TSH release. During thyroid hormone production, only about 20% of T3 is produced within the thyroid follicular cells themselves. The remaining 80% is produced in the peripheral tissues from the deiodination of T4.12
Although the underlying pathoph ysiological mechanisms surrounding the body's shift from a compensated hyper- or hypothyroid state into a thyroid crisis is poorly defined, it seems intuitive. A mismatch between supply and demand of thyroid hormone secondary to some insult pushes the body into a state of severe decompensation, affecting the multiple systems that are regulated by thyroid hormone.
Cardiovascular effects of thyroid hormone include a direct increase in peripheral tissue oxygen consumption and tissue thermogenesis, indirectly increasing cardiac output, and direct chronotropic and inotropic effects on the heart. A resting sinus tachycardia is the most common cardiovascular sign in hyperthyroidism and exhibits a circadian rhythm more pronounced than in euthyroid patients.13,14
Thyroid hormone effectively decreases systemic vascular resistance by dilating the resistance arterioles of the peripheral circulation. The clinical end result is the tachycardia, widened pulse pressure, and increased cardiac output typical of hyperthyroidism. Although this clinical picture may resemble a state of hyperadrenergic activity, serum catecholamine levels are actually low to normal. However, the concept of a hyperadrenergic state is useful for the practicing physician, as adrenergic blockade is one of the main components of management in thyroid storm. Conversely, in myxedema coma, patients exhibit bradycardia, hypotension, and hypothermia due to the lack of cardiovascular support from the thyroid hormone.15 Thyroid hormone also has important effects on pulmonary, neuromuscular, and renal physiology. Hyperthyroidism contributes to respiratory muscle weakness, decreased cardiopulmonary efficiency, and reduced exercise capacity as measured by spirometry and spiroergometry (direct breath-to-breath gas exchange measurements during exercise).16 Hypothyroidism alters ventilation, as manifested by a decreased central response to hypoxia and hypercapnia resulting in a respiratory acidosis. This blunted response results in an attenuated increase in minute ventilation to rising CO2 levels. Conversely, these atients are susceptible to respiratory alkalosis, most commonly seen after overaggressive mechanical ventilation. The pathophysiology behind this particular phenomenon lies in the reduced basal metabolic rate and diminished CO2 production secondary to low levels of circulating thyroid hormone.17 As a result, although intubation and mechanical ventilation may be life saving in the hypoxic, hypercapneic patient, clinicians should be cautious about overly aggressive correction of the hypercapnia, as this may induce respiratory alkalosis.18
In addition to directly affecting ventilatory drive, hypothyroidism affects both respiratory and skeletal muscle function. Investigators report diaphragmatic weakness and fatigue as measured by inspiratory pressures and cycle times compared with maximum transdiaphragmatic pressures and total respiratory cycle times. In concert with delayed phrenic nerve conduction velocities, the end clinical result is diaphragmatic dysfunction c using a restrictive respiratory pattern that contributes to hypoxia and hypercapnia. Significant skeletal muscle atrophy, up to 50% of total muscle mass, is also related to chronic hypothyroidism, secondary to increased skeletal muscle cell permeability and decreased adenosine triphosphate (ATP) production. Thyroid hormone replacement improves all of these conditions, but full recovery may take months.
The renal effects of thyroid hormone are an increase in blood volume and preload, which contributes to further increases in cardiac output. In addition, thyroid hormone can stimulate erythropoietin secretion.