The Art and Science of Infusion Nursing Angela M. Leung , MD, MSc Thyroid Emergencies cal manifestations, diagnostic methods, and treatments of ABSTRACT hypothyroidism and hyperthyroidism, both in the Myxedema coma and thyroid storm are thyroid nonacute and life-threatening forms of these diseases. emergencies associated with increased mortality. Prompt recognition of these states—which repre- sent the severe, life-threatening conditions of THYROID HORMONE PRODUCTION AND METABOLISM extremely reduced or elevated circulating thyroid hormone concentrations, respectively—is neces- sary to initiate treatment. Management of myxe- The normal physiology of the hypothalamic-pituitary- dema coma and thyroid storm requires both med- thyroid axis involves the production of T4 and T3 by the thyroid gland, a process that is regulated by thyroid- ical and supportive therapies and should be treated stimulating hormone (TSH) secreted by the pituitary, in an intensive care unit setting. which is, in turn, regulated by thyrotropin-releasing hor- Key words: hypothyroidism , hyperthyroidism , mone (TRH) secreted by the hypothalamus. Both serum ICU , myxedema coma , thyroid emergencies , T4 and T3 concentrations act as negative feedback regu- thyroid storm lators of TSH and TRH secretion, but can be altered by environmental conditions—including food availability he thyroid is a 15- to 20-gram gland located and temperature—and disease states, such as infection. 1 in the anterior neck. It is responsible for the Thyroid hormone synthesis is achieved first through production of the thyroid hormones T4 (thy- active transport of circulating iodide, which is taken in roxine) and T3 (triiodothyronine). Various from the diet, by the sodium/iodide symporter located at factors can affect thyroid hormone synthesis, the basolateral membrane of the thyroid follicular cell. 2 including acute illness, coexisting morbidities, and certain Iodide then becomes oxidized by thyroid peroxidase T medications. Both the states of low thyroid hormone con- (TPO) and hydrogen peroxide at the apical membrane, centrations (hypothyroidism) and thyroid hormone excess which then attaches to the tyrosyl residues on thyroglob- (thyrotoxicosis) can be transient or permanent. The ulin (Tg) to produce monoiodotyrosine (MIT) and diio- decompensated, severe forms of hypothyroidism and dotyrosine (DIT). MIT and DIT are the precursors to the hyperthyroidism, termed myxedema coma and thyroid thyroid hormones, which are produced by the linkage of storm , are associated with increased morbidity and mor- 2 DIT molecules to form T4 and the linkage of MIT and tality. Prompt recognition of both conditions is necessary DIT to produce T3. Release of T4 and T3 into the circu- to initiate treatment and supportive measures. This lation results from the digestion of Tg in MIT and DIT review will summarize the essential principles of the clini- by endosomal and lysosomal proteases. The metabolic effects of thyroid hormone action result Author Affiliations: Division of Endocrinology, David Geffen from the binding of the thyroid hormone to thyroid hor- School of Medicine at UCLA, and the VA Greater Los Angeles mone transporters located in specific target tissues, which Healthcare System, Los Angeles, California. Angela M. Leung, MD, MSc, is an assistant clinical professor of is mediated by the thyroid hormone nuclear receptor (TR) 3 medicine in the Division of Endocrinology at the David Geffen that is encoded by the genes TR α and TR β . While the School of Medicine at the University of California, Los Angeles, sole source of T4 is the thyroid gland, the majority and the VA Greater Los Angeles Healthcare System, both in Los Angeles, California. (approximately 80%) of T3 is produced from the The author received funding from the National Institutes of Health, extrathyroidal conversion of T4 to T3 by the action of the NIH 7K23HD068552. The author has no other potential conflicts of 5´-deiodinase enzymes—D1 or D2—located in the liver, interest to disclose. brain, brown adipose tissue, and muscles. 4 T4 can also be Corresponding Author: Angela M. Leung, MD, MSc, VA Greater converted to the inactive thyroid hormones, reverse T3 or Los Angeles Healthcare Sysem, Divison of Endocrinology (111D), 11301 Wilshire Blvd, Los Angeles, CA 90073 ( AMLeung@mednet. T2, by the 5´-deiodinase D3. The activity and expression ucla.edu ). of the deiodinases are specific to different tissues and envi- DOI: 10.1097/NAN.0000000000000186 ronmental conditions. VOLUME 39 | NUMBER 5 | SEPTEMBER/OCTOBER 2016 Copyright © 2016 Infusion Nurses Society 281 Copyright © 2016 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited. SERUM THYROID FUNCTION AND ANTIBODIES TABLE 1 Signs and Symptoms Serum TSH is the most sensitive test to suggest thyroid dysfunction, because of the logarithmic-linear relation- of Hypothyroidism ship between serum TSH and thyroid hormone levels. General Overt thyroid dysfunction, whether referring to hypo- thyroidism or hyperthyroidism, is defined by the sole Fatigue abnormality of an elevated serum TSH concentration, Lethargy while subclinical thyroid dysfunction refers to both Weight gain elevated serum TSH and decreased T3 and/or T4 con- Sleepiness centrations. The range of subclinical to overt thyroid dysfunction can be regarded as a continuum of increas- Cold intolerance ingly severe biochemical thyroid disease, which inciden- Skin and hair tally may or may not correlate to the severity of any Dry, thick skin corresponding symptoms, if present. Coarse hair Eyebrow thinning HYPOTHYROIDISM Brittle nails Decreased perspiration Hypothyroidism refers to the state of low circulating Cardiovascular system thyroid hormones. In 2 large US population-based stud- Bradycardia ies of data collected in the 1980s to the 1990s, the preva- lence of overt hypothyroidism ranged from 0.3% to Elevation of blood pressure 0.4%, while that of subclinical hypothyroidism ranged Hyperlipidemia from 4.3% to 8.5%, among the general population.5 , 6 Respiratory system The most common etiology of hypothyroidism in the Shortness of breath United States is Hashimoto’s thyroiditis, an autoimmune Hoarse voice disease that is more prevalent among older women; nutritional iodine deficiency is the most common etiology Sleep apnea worldwide. Additional etiologies of hypothyroidism Gastrointestinal system include a history of thyroidectomy, radioactive iodine Constipation therapy, and, less commonly, decreased TSH production Decreased appetite by the pituitary. Predisposition factors for the develop- ment of hypothyroidism include thyroid autoimmunity Reproductive system (which can be assessed by the determination of serum Menstrual cycle irregularities thyroid autoantibodies, such as TPO and [Tg] antibody Infertility titers), the use of certain medications (ie, lithium, ami- Musculoskeletal system odarone, interferon-alpha), and excess iodine exposure (ie, from iodinated contrast radiographic studies), in Arthralgia which individuals with a history of thyroid disease are at Neurological system higher risk of iodine-induced hypothyroidism. 7 Paresthesia Thyroid hormone is important for the metabolic func- Depression tions of many major organs, including the heart, brain, Mental impairment liver, and muscle. Signs and symptoms of hypothyroidism are widely variable ( Table 1 ), often subtle, and may Slow movements include fatigue, malaise, weight gain, dry and puffy skin, Hyporeflexia constipation, cold intolerance, altered cognition, and hyporeflexia. In children, there may be stunted growth, and in women, menstrual abnormalities may be present. fetus, and young children. As thyroid hormone is cru- cial for the complex processes of neurodevelopment and 8 Hypothyroidism Among Women of growth, which begins in the first trimester of pregnan- Reproductive Age and in Children cy and continues into the first few years of infancy, these groups are especially susceptible to the effects of Normal thyroid function is particularly important even mild thyroid dysfunction. Several studies have among pregnant and lactating women, the developing demonstrated that low thyroid hormone levels among 282 Copyright © 2016 Infusion Nurses Society Journal of Infusion Nursing Copyright © 2016 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited. pregnant women are associated with increased risks of impaired state of the patient. Suggested regimens for the preterm delivery, spontaneous miscarriage, fetal death, initial and maintenance doses of thyroid hormone in a and cognitive deficits, 9 including a decrement in intelli- patient with myxedema coma are provided in Table 2 . gence quotient and memory scores of the offspring, In general, a loading dose of 200 to 400 μ g IV levothy- compared with euthyroid women. 10-13 Neuroimaging roxine (T4) is to be followed by a maintenance dose of studies also show abnormalities of hippocampal and 1.6 μ g/kg/d when given orally or 75% of this when corpus callosum size, and of gray matter, among chil- given intravenously; consideration can also be made for dren with a form of low thyroid hormone levels at birth the coadministration of liothyronine (T3), since T4 to termed congenital hypothyroidism . 14 , 15 T3 conversion may be impaired in patients with myxe- dema coma. 20 It is important to note that IV thyroid hormone replacement should be administered only as a Myxedema Coma push through a syringe, rather than through infusion tubing, in which up to 40% of the starting concentra-