Antithyroid drugs for hyperthyroidism.
Graves' disease, the most common form of hyperthyroidism, is named after Irish physician Robert Graves who described this form of hyperthyroidism over 150 years ago. GD is triggered by an abnormality of the body's immune system. The immune system is designed to protect the body from foreign invaders, such as vimses and bacteria. In GD, lymphocytes make antibodies against the thyroid cells, causing an overproduction in thyroid hormone. Key physical findings in a person with GD may include a bulging of the eyes (Graves' ophthalmopathy) and, in rare instances, a lumpy reddish thickening of the skin in the shin area (pretibial myxedema) (ATA, 2015a).
TMNG is the second leading cause of hyperthyroidism. It involves the occurrence of one or more nodules in the thyroid that may grow and increase in activity, causing hypersecretion of thyroid hormone. Approximately 5% of these nodules are cancerous (ATA, 2015b).
Toxic adenoma is a less common cause of hyperthyroidism. A single nodule grows on the thyroid gland, causing it to enlarge and produce increased amounts of thyroid hormone. If the increased hormone production comes from a single nodule in the gland, the condition is termed toxic adenoma (ATA, 2015b).
Some symptoms experienced by a patient with thyrotoxicosis, regardless of the cause, include nervousness, irritability, increased perspiration, anxiety, racing heart, difficulty sleeping, thinning skin, weight loss, or muscle weakness (ATA, 2014). The condition typically is diagnosed with a complete physical examination and assessment of the body's serum thyroid hormones (TSH, T4). Additional diagnostics for hyperthyroidism may include a thyroid scan and thyroid uptake (ATA, 2014).
Treatment for hyperthyroidism varies, depending on the patient's preference and coexisting medical conditions. Evidence-based guide lines for treating hyperthyroidism were developed by the ATA in conjunction with the American Association of Clinical Endocrinologists. A systematic literature review using PubMed with additional publications was evaluated, resulting in 100 evidence-based recommendations to care for patients with thyrotoxicosis (Bahn et al., 2011). Pharmacologic treatments with strength of recommendation and quality of evidence are described in Table 1.
Information on the pharmacologic treatment for hyperthyroidism will be provided in this article, including use of beta-blockers and radioactive iodine therapy. However, the main focus is to describe the use of antithyroid medications in the treatment of hyperthyroidism and nursing considerations in the care of patients taking these medications.
Beta-Blockers and [sup.131]I in the Treatment of Hyperthyroidism
Beta-blockers often are added as adjunct therapy in the initial phases of antithyroid drug treatment to control cardiac symptoms (e.g., tachycardia) of hyperthyroidism (Bartalena, 2013). According to ATA clinical guidelines, beta-blockers should be prescribed to older adults with symptomatic thyrotoxicosis, as well as other patients with thyrotoxicosis with resting heart rates greater than 90 beats per minute. Coexistent cardiovascular disease in patients with thyrotoxicosis is also an indication for use of beta-blockers as part of hyperthyroidism treatment protocols. Furthermore, clinical guidelines recommend all patients with symptomatic thyrotoxicosis should be considered for administration of beta-blockers to reduce cardiovascular symptoms (Bahn et al., 2011).
Radioactive iodine ([sup.131]I) can be used as first-line treatment for GD with hyperthyroidism. It is also the treatment of choice for relapse cases. [sup.131]I therapy appears to be the treatment of choice in the United States, while antithyroid medications are used more commonly as first-line treatment in Europe and Asia (Franklyn & Boelaert, 2012). However, more prescriptions for antithyroid medications are being written in this country, potentially signaling a shift in the primary treatment of hyperthyroidism (Burch, Burman, & Cooper, 2012).
[sup.131]I is an effective treatment for GD with hyperthyroidism because it causes hypothyroidism through gradual necrosis of the thyroid cells (Bartalena, 2013). When [sup.131]I is administered, the goal is to achieve hypothyroidism instead of euthyroid levels. A low dose of [sup.131]I used to achieve euthyroidism is associated with high rates of recurrence of hyperthyroidism (Bahn et al., 2011). [sup.131]I can be given in fixed doses or calculated doses according to estimated thyroid size and uptake of [sup.131]I 24 hours after administration (Bartalena, 2013). Use of higher doses of [sup.131]I is associated with better treatment success rate and earlier achievement of cure (Sztal-Mazer et al., 2012). Methimazole usually is recommended 5-7 days after [sup.131]I therapy, then will be withdrawn as radioactive therapy becomes effective (Franklyn & Boelaert, 2012). Clinical guidelines on administration should be followed closely to ensure radiation safety for patients and close family members (Bahn et al., 2011).
[sup.131]I treatment is contraindicated in the following situations: pregnancy, lactation, or coexisting or suspected thyroid cancer. To maintain safety, [sup.131]I may not be the best therapy for individuals who have difficulty adhering to radiation safety guidelines. Radioactive iodine therapy should not be given to women planning a pregnancy within 4-6 months (Bahn et al., 2011).
Antithyroid hormones, also known as thionamides, often are prescribed for treatment of hyperthyroidism and its distressing symptoms. Two antithyroid medications are currently available: methimazole (Tapazole[R]) and propylthiouracil (PTU). Both drugs suppress thyroid hormones by blocking oxidation of iodine in the thyroid gland, which subsequently blocks synthesis of T3 and T4 (Kizior, Hodgson, Hodgson, & Witmer, 2016; Smith, 2016). These medications do not affect circulating and stored T3 and T4 (Smith, 2016). They are metabolized by the liver and excreted in urine (Smith, 2016).
Methimazole should be prescribed to every patient who chooses to use antithyroid therapy as treatment for Grave's disease (Bahn et al., 2011) to reduce the effects of hyperthyroidism. It also is given prior to surgery or radiotherapy of the thyroid gland (Wilson, Shannon, & Shields, 2014). Methimazole should not be prescribed in the first trimester of pregnancy, when PTU is a preferred treatment of thyroid storm, and in patients with minor reactions to methimazole who refuse radioactive iodine or surgery as treatment (Bahn et al., 2011). Methimazole is metabolized by the liver more rapidly than PTU (Smith, 2016). It also has a much longer half-life, which means less frequent dosing per day (Adams, Holland, & Urban, 2014).
Usual dosage for methimazole is 15-60 mg/day administered in divided doses every 8 hours (Wilson et al., 2014). Drug-drug interactions for methimazole include increased bone marrow depression when combined with antineoplastics, decreased antithyroid effect in combination with amiodarone (Cordarone[R]), and increased risk for agranulocytosis with phenothiazines. It also may elicit an increased therapeutic effect of warfarin (Coumadin[R]) and digoxin (Lanoxin[R]), potentially placing the patient at risk for bleeding or digoxin toxicity (Vallerand, Sanoski, & Deglin, 2015).
The most common side effects of methimazole are rashes and drowsiness (Edmunds, 2016; Vallerand et al., 2015). Scalp abnormalities also have been reported increasingly with methimazole use (Lilley, Collins, & Snyder, 2012). Potential life-threatening adverse effects of methimazole include leukopenia, thrombocytopenia, and agranulocytosis (Wilson et al., 2014). Because methimazole is metabolized by the liver, a risk for hepatotoxicity exists. Jun and colleagues (2015) found severe hepatotoxicity usually occurs within the first 3 months of initiating antithyroid therapy. They also analyzed 90 cases of antithyroid-induced hepatotoxicity and found no significant difference between incidence between methimazole and PTU groups. Through a population-based cohort study conducted in Taiwan, Wang, Lee, Huang, Chu, and Hsieh (2014) found methimazole was associated with increased risk for development of dose-dependent drug-induced hepatitis compared to PTU. Data also showed methimazole and PTU users had similar risk for developing acute liver failure and cholestasis.
Propylthiouracil is prescribed for patients diagnosed with Graves' disease with hyperthyroidism or toxic multinodular goiter who cannot tolerate methimazole (U.S. Food and Drug Administration [FDA], 2015). PTU also is used as a palliative treatment for patients with hyperthyroidism for whom surgery or radioactive treatment is not an option. For patients undergoing thyroidectomy or radioactive iodine therapy but cannot tolerate methimazole, PTU is given as adjunct therapy to help ameliorate symptoms of hyperthyroidism (Kizior et al., 2016). In addition to its main mechanism of action on thyroid hormone synthesis in the thyroid gland, PTU blocks the conversion of T4 into T3 (more biologically active form) (Smith, 2016).
PTU should not be given to pregnant women due to potential teratogenic effects (Vallerand et al., 2015). In April 2010, the FDA (2015) added a black box warning to PTU due to increased reports of severe liver injury and acute liver failure that could be fatal to adults and children. PTU should be given cautiously to patients who are taking other medications that may cause agranulocytosis (e.g., phenothiazines) (Kizior et al., 2016; Vallerand et al., 2015). Similar to methimazole, PTU may increase the concentration of digoxin because patients become more euthyroid during therapy and experience increased risk for digoxin toxicity. PTU also may increase the effects of oral anticoagulants, which could place the patient at increased risk for bleeding (Kizior et al., 2016).
PTU is administered around the clock (usually every 8 hours). Initial dosage for adults is 300-400 mg per day in divided doses. For older adults, initial dose is lower at 150-300 mg/day in divided doses. Maintenance doses are usually 100-150 mg/day administered in divided doses every 8-12 hours (Kizior et al., 2016).
Side effects frequently reported by patients include urticaria, skin rash, pruritus, abnormal hair loss, headache, and paresthesia (Kizior et al., 2016; Wilson et al., 2014). Life-threatening adverse effects include agranulocytosis and pancytopenia (decreased levels of all blood cells) due to bone marrow suppression (Wilson et al., 2014). If patients experience pancytopenia, they are at risk for anemia, infection, and bleeding (Kizior et al., 2016).
Studies on the Effects of Antithyroid Medications
Sundaresh and colleagues (2013) conducted a meta-analysis to compare the effectiveness of antithyroid medications, [sup.131]I, and thyroidectomy as therapies for GD with hyperthyroidism. Their primary outcome was to determine relapse rates for the three treatment options. Their secondary outcome was to present data regarding adverse effects of antithyroid medications. Researchers found relatively higher risk of relapse with the antithyroid drugs (52.7%, or 352 out of 667). They also found no significant difference in relapse between [sup.131]I and surgery. Common adverse effects found in use of antithyroid medications were dermatologic complications with methimazole and hepatotoxic effects with PTU.
In a study comparing the therapeutic effects of methimazole and PTU, Nakamura and co-authors (2013) found methimazole 30 mg/ day normalized free T4 in more patients compared to PTU 300 mg/day and methimazole 15 mg/day after 12 weeks of treatment. Authors concluded a dosage of 15 mg of methimazole daily may be suitable for patients diagnosed with mild-to-moderate GD with hyperthyroidism. Methimazole 30 mg/day can be given to patients with severe cases. They also recommended PTU not be prescribed as an initial treatment to patients with hyperthyroidism due to its hepatotoxic effects.
In another study, long, continuous methimazole was superior as therapy for diffuse toxic goiter compared to [sup.131]I therapy (Azizi et al., 2012). Results showed more incidents of elevated TSH, triglycerides, and early diastolic annular velocity in [sup.131]I. Patients taking methimazole also showed better scores in neuropsychology tests, specifically mood, direction, logical memory, repeated numbers, and intelligence quotient.
Recently, medical researchers compared the effectiveness of methimazole 30 mg/day with methimazole 15 mg/day dosage plus inorganic iodine (potassium iodide) 38 mg/day for treatment of GD with moderate-to-severe hyperthyroidism (Shotaro et al., 2015). Results suggested methimazole 15 mg/day plus iodine provides superior treatment to methimazole 30 mg/day. The authors recommended further research into the methimazole-iodine combination.
Treating Thyrotoxic Crisis
Patients with untreated or inadequately treated hyperthyroidism are at risk for thyrotoxic crisis (also known as thyroid storm). High levels of stress are the most common precipitating factor of thyroid storm, usually caused by underlying illness, surgery, general anesthesia, or infection. The underlying pathophysiologic process of thyrotoxic crisis is relatively unknown. Signs and symptoms include high levels of circulating thyroid hormones, enhanced cellular response to thyroid hormones, and hyperactivity of the sympathetic nervous system (Sole, Klein, & Moseley, 2013).
Patients experiencing thyrotoxic crisis require immediate treatment. Bahn and colleagues (2011) recommended a multimodal approach to treat patients with signs and symptoms of this condition. Pharmacotherapies include beta-blockers, antithyroid medications, inorganic iodide, corticosteroids, and acetaminophen. Symptomatic interventions include cooling blankets, volume resuscitation, respiratory support, and monitoring in the intensive care unit.
Nursing Considerations for Antithyroid Medications
Methimazole and PTU should not be given to pregnant women as these drugs may cause congenital abnormalities in the fetus (Wilson et al., 2014). In a meta-analysis of cohort studies, Li and colleagues (2015) recommended minimal to no use of antithyroid medications for pregnant women with hyperthyroidism.
Prior to medication administration, baseline assessment of hyperthyroid signs and symptoms should be completed. Data to document include weight, heart rate, and serum T3, T4, and TSH. Other laboratory results that need to be monitored include liver function tests (including bilirubin and transaminases), complete blood count with differential, and platelet count (Bahn et al., 2011; Lilley et al., 2016; Wilson et al., 2014). Health care providers should be aware 10% of patients with hyperthyroidism may have leukopenia less than 4,000 cells/mm3 and relative granulocytopenia (Wilson et al., 2014). As therapy progresses, providers will monitor signs of therapeutic effects, such as weight gain and lowered heart rate. Weight should be monitored at least twice weekly (Vallerand et al., 2015).
Patients with greatly enlarged thyroids should be informed that achieving satisfactory euthyroid state through antithyroid drug therapy may be delayed. Patients who undergo thyroidectomy also should be advised if euthyroid levels have not been achieved by surgery alone, antithyroid drug treatment will be reinstituted (Wilson et al., 2014).
Liver function tests should be assessed in patients taking PTU who experience the following adverse effects: pruritic rash, jaundice, light-colored stool or dark urine, joint pain, abdominal pain or bloating, anorexia, nausea, or fatigue. Routine monitoring of white blood cell count is not recommended. A differential white blood cell count only should be obtained during febrile illness and at the onset of sore throat in all patients taking antithyroid medication (Bahn et al., 2011). Sore throat is usually the first sign of drug-induced agranulocytosis. Agranulocytosis may occur as long as 4 months after initiation of antithyroid therapy (Kizior et al., 2016). Patients also should report signs of low prothrombin promptly to providers (e.g., large bruises, petechiae, purpura, unexplained bleeding) (Wilson et al., 2014).
Patients should be taught to take heart rates accurately and reminded to check their heart rates daily (Kizior et al., 2016; Wilson et al., 2014). Medications should be taken around the clock, and time between doses should be spaced evenly (Kizior et al., 2016). Patients should be informed to avoid over-thecounter medications for asthma or cough treatment without checking with the provider. These medications may contain iodide, which would decrease the effects of antithyroid medication. Signs of inadequate therapy or thyrotoxicosis include diarrhea, fever, irritability, listlessness, vomiting, and weakness. Patients should report these signs to the provider immediately for adequate adjustment of treatment (Wilson et al., 2014). Patients also should check with their providers to determine if iodized salt and seafood (e.g., shellfish) could be included in their dietary choices (Vallerand et al., 2015; Wilson et al., 2014). Methimazole and PTU may cause drowsiness. Patients should be reminded not to drive or handle dangerous equipment until effects of the medication are known (Vallerand et al., 2015).
Hyperthyroidism is a treatable endocrine disorder. Treatments vary based on country and are individualized to the person. Having a working knowledge of the current evidence-based guidelines for treating hyperthyroidism aids in improved patient care. While the choices for pharmacologic treatment are limited, they are an effective component in treating hyperthyroidism. Nurses should be aware of the varying symptoms of hyperthyroidism. They also should have a working knowledge of the three main causes of hyperthyroidism, especially GD. They will be prepared to address potential complications as they care for medical-surgical patients.
Adams, M., Holland, N., & Urban, C. (2014). Pharmacology for nurses: A pathophysiologic approach. Upper Saddle River, NJ: Pearson Education.
American Thyroid Association (ATA). (2015a). Graves' disease. Retrieved from http://www.thyroid.org/graves-disease/
American Thyroid Association (ATA). (2015b). Thyroid nodules. Retrieved from http://www.thyroid.org/thyroid-nodules/
American Thyroid Association (ATA). (2014). Hyperthyroidism. Retrieved from http://www.thyroid.org/hyperthyroidism/
Azizi, F., Yousefi, V., Bahrainian, A., Sheikholeslami, F., Tohidi, M., & Merabi, Y. (2012). Long-term continuous methimazole or radioiodine treatment for hyperthyroidism. Archives of Iranian Medicine, 15(8), 477-484.
Bahn, R.S., Burch, H.B., Cooper, D.S., Garber, J.R., Greenlee, C., Klein, I., ... Stan, M.N. (2011). Hyperthyroidism and other causes of thyrotoxicosis: Management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocrine Practice, 17(3), e1-e65.
Bartalena, L. (2013). Diagnosis and management of Graves' disease: A global overview. Nature Reviews Endocrinology, 9, 724-734.
Burch, H.B., Burman, K.D., & Cooper, D.S. (2012). A 2011 survey of clinical practice patterns in the management of Graves' disease. The Journal of Clinical Endocrinology & Metabolism, 97(12), 4549-4558.
Edmunds, M.W. (2016). Introduction to clinical pharmacology (8th ed.). St. Louis, MO: Elsevier.
Franklyn, J.A., & Boelaert, K. (2012). Thyrotoxicosis. Lancet, 379 1155-1166.
Jun, Y., Lin-fa, L., Qin, X., Jun, Z., Wan-wen, W., Yang-jun, Z., & Meng-jie, D. (2015). Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicty over 13 years in China. Thyroid, 25(3), 278-283.
Kizior, R., Hodgson, B.B., Hodgson, K.J., & Witmer, J.B. (2016). Saunders nursing drug handbook 2016. St. Louis, MO: Elsevier.
Li, H., Zheng, J., Luo, J., Zeng, R., Feng, N., Zhu, N., & Feng, Q. (2015). Congenital abnormalities in children exposed to antithyroid drugs in-utero: A meta-analysis of cohort studies. PLOS One, 10(5), e0126610. doi:10.1371/journal.pone. 0126610
Lilley, L.L., Collins, S.R., & Snyder, J.S. (2012). Pharmacology and the nursing process (7th ed.). St. Louis, MO: Elsevier.
Nakamura, H., Noh, J.Y., Itoh, K., Fukata, S., Miyauchi, A., & Hamada, N. (2013). Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease. The Journal of Clinical Endocrinology & Metabolism, 92(6), 2157-2162. doi:10. 1210/jc.2006-2135
Sargis, R. (2015). Thyroid gland overview: A major player in regulating your metabolism. Retrieved from http://www.endo crineweb.com/endocrinology/overviewthyroid
Shotaro, S., Yoshimura, N.J., Shiori, S., Miho, S., Shigemitsu, Y., Masako, M., ... Matsuo, T. (2015). Comparison of efficacy and adverse effects between methimazole 15 mg + inorganic iodine and methimazole 30 mg/day as initial therapy for Graves' disease patients with moderate to severe hyperthyroidism. Thyroid, 25(1), 43-50.
Smith, B.T. (2016). Pharmacology for nurses. Burlington, MA: Jones & Bartlett Learning.
Sole, M L., Klein, D.G., & Moseley, M.J. (2013). Introduction to critical care nursing (6th ed). St. Louis, MO: Elsevier.
Sundaresh, V., Brito, J.P., Wang, Z., Prokop, L.J., Stan, M.N., Murad, M.H., & Bahn, R.S. (2013). Comparative effectiveness of therapies for Graves' hyperthyroidism: A systematic review and network metaanalysis. The Journal of Clinical Endocrinology & Metabolism, 98(9), 3671-3677.
Sztal-Mazer, S., Nakatani, V.Y., Bortolini, L.G., Boguszewski, C.L., Graf, H., & de Carvalho, G.A. (2012). Evidence for higher success rates and successful treatment earlier in Graves' disease with higher radioactive iodine doses. Thyroid, 22(10), 991-995.
U.S. Food and Drug Administration (FDA). (2015). Propylthiouracil information. Retrieved from http://www.fda.gov/ drugs/drugsafety/postmarketdrugsafety informationforpatientsandproviders/ucm209038.htm
Vallerand, A.H., Sanoski, C.A., & Deglin, J.H. (2015). Davis's drug guide for nurses (14th ed.). Philadelphia, PA: F.A. Davis.
Wang, M.T., Lee, W.J., Huang, T.Y., Chu, C.L., & Hsieh, C.H. (2014). Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: A population-based cohort study. British Journal of Clinical Pharmacology, 78(3), 619-629.
Wilson, B.A., Shannon, M.T., & Shields, K.M. (2014). Pearson nurse's drug guide 2014. Upper Saddle River, NJ: Pearson Education.
Rhea Faye D. Felicilda-Reynaldo, EdD, RN, is Associate Professor, Department of Nursing, Missouri State University, Springfield, MO; and MEDSURG Nursing Editorial Board Member. For comments and to suggest topics for the "Nursing Pharmacology" column, contact email@example.com.
Maria Kenneally, DNP, FNP-BC, is Family Nurse Practitioner, Gilbert Center for Family Medicine, Gilbert, AZ.
Instructions For Continuing Nursing Education Contact Hours
Antithyroid Drugs for Hyperthyroidism
Deadline for Submission: February 28, 2018
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TABLE 1. Pharmacologic Treatments with Strength of Recommendation and Quality of Evidence Strength of Quality of Medication Recommendation Evidence Beta-adrenergic blocker 1 * ++ ** Radioactive iodine treatment 1 * ++ ** Antithyroid medication (methimazole, 1 * ++ ** propylthiouracil) * 1 = Strong recommendation (for or against). Applies to most patients in most circumstances. Benefits clearly outweigh the risk (or vice versa) ** ++ = Moderate quality; studies with methodological flaws, showing inconsistent or indirect evidence Source: Bahn et al., 2011.
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|Title Annotation:||CNE SERIES: Nursing Pharmacology|
|Author:||Felicilda-Reynaldo, Rhea Faye D.; Kenneally, Maria|
|Date:||Jan 1, 2016|
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