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Home , Diiodotyrosine, Hypothyroidism, Liothyronine, Liotrix, Perchlorate, Pertechnetate

: Overview and Treatment Options

Authors: Laura P. Stegall, Pharm.D. , Harrison School of Pharmacy, Auburn University;

Mary Cathryn Holladay, Pharm.D., Harrison School of Pharmacy, Auburn University;

Amr M. Abdelrehiem, Pharm.D., Harrison School of Pharmacy, Auburn University;

Bernie R. Olin, Pharm.D., Associate Clinical Professor and Director Drug Information Center, Harrison School of Pharmacy, Auburn University

Universal Activity #: 0178-0000-14-105-H01-P | 1.25 contact hours (.125 CEUs)

Initial Release Date: November 25, 2014 | Expires May. 1, 2016

Alabama Pharmacy Association | 334.271.4222 | www.aparx.org | [email protected]

Winter 2014: Continuing EDUCATION | www.APARX.org 1 Educational Objectives After the completion of this activity pharmacists will be able to: • List risk factors for the development of hypothyroidism. • Describe the pathophysiology of hypothyroidism. • Discuss treatment options for hypothyroidism.

Introduction hypothyroidism; however, in a , age of the pregnant Hypothyroidism is defined as an endocrinologic disorder woman did not increase risk.5 resulting from decreased production and affects A patient is considered at high risk for the development of an estimated 1.5% to 2% of women and 0.2% of men worldwide.1 hypothyroidism if he/she is a postpartum woman; has a family It is categorized into either overt hypothyroidism or subclinical history of autoimmune disorders; has an autoimmune endocrine hypothyroidism based on the level of dysfunction. In the Third condition such as mellitus type I, , National Health and Nutrition Examination Survey, 16,533 people Addison’s disease, or ovarian failure; has had previous head, neck, representing the geographic and ethnic distribution of the United or thyroid irradiation or surgery; has a non-endocrine autoimmune States population with no prior history of thyroid disorder had disorder such as celiac disease, , pernicious their levels of serum thyroid-stimulating hormone (TSH) and , Sjögren’s syndrome, or multiple sclerosis; has primary 1,4 total thyroxine (T4) measured. As a result of this survey, 0.3% pulmonary ; or has Down or . of the study population was found to have overt hypothyroidism Although diabetes mellitus type II is not currently a risk factor for and 4.3% of the study population was found to have subclinical hypothyroidism, some studies have concluded that in some ethnic hypothyroidism.2 Hypothyroidism incidence increases with age groups, such as Saudi Arabians, type II diabetes does increase the risk and is three to four times more prevalent in females than males; for hypothyroidism.6 Caucasian and Mexican-Americans are also more likely to have Certain genetic factors, specifically polymorphisms with the hypothyroidism than African-Americans.1,2 HLA-DR can increase the risk for Hashimoto’s .7 Hypothyroidism is classified into either primary or secondary Other risk factors for overt hypothyroidism include deficiency hypothyroidism. Causes of primary hypothyroidism include often associated with endemic goiter and cretinism, the presence of Hashimoto’s thyroiditis, iatrogenic hypothyroidism, iodine subclinical hypothyroidism, and the presence of infiltrative disorders deficiency, defects, thyroid hypoplasia, and , such as hemochromatosis, sarcoidosis, , scleroderma, while causes of secondary hypothyroidism include pituitary and cystinosis, and Riedel’s thyroiditis. hypothalamic disease.1 Hypothyroidism can also be congenital, with the incidence of congenital hypothyroidism increasing by Pathophysiology 3% per year in the United States.3 The most common cause of In order to understand the pathophysiology of hypothyroidism, hypothyroidism worldwide is ; however in iodine one must first understand normal thyroid hormone physiology, sufficient countries, such as the United States, the most common including normal thyroid hormone synthesis. cause of hypothyroidism is Hashimoto’s thyroiditis, a chronic , a large glycoprotein synthesized within the , accounting for 60% of all hypothyroidism thyroid cells, provides for iodination to form active thyroid cases.1,2,4 Untreated hypothyroidism can lead to detrimental . This process begins when ingested iodine converts to consequences, but often can go untreated for many years due to non- iodide and is actively transported into a via a specific symptoms.1 sodium/iodide symporter. Iodination of tyrosine on thyroglobulin by creates monoiodotyrosine (MIT) and Risk Factors (DIT). Sequentially, thyroid peroxidase combines

Women are more likely to be diagnosed with hypothyroidism either two molecules of DIT to form thyroxine (T4) or one molecule than men; specifically autoimmune thyroid diseases are of MIT with one molecule of DIT to form (T3). approximately five to ten times more common in females than In the case of iodine deficiency, an increased ratio of MIT to DIT 4 males. Although being a woman is a risk factor for hypothyroidism, occurs to increase production of T3 since it is four times more risk increases in both men and women with advancing age. potent than T4. However, T4 is solely formed within the thyroid

Being a pregnant woman is also a risk factor for development of gland whereas only 20% of T3 is formed there. The majority of T3

Table 1. T3 Production 5’-monodeiodinase Tissue location Preferred substrate Role

Type I Thyroid, liver, kidney rT3>T4>T3 Extracellular T3 production for peripheral tissues

Type II Pituitary, thyroid, central nervous T4>T3 Intracellular T3 production system (CNS), brown adipose tissue

Type III Placenta, developing brain, skin T3>T4 Inactivation of both

Adapted from DiPiro JT, et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 20111

2 Alabama pharmacy ASSOCIATION | WINTER 2014: Continuing EDUCATION is created by breakdown of T4 in peripheral tissue. Breakdown of the thyroid gland; thyroid hypoplasia; uncommon infection from

T4 is catalyzed by three types of 5’-monodeiodinases listed in Table Pneumocystitis jiroveci; and maternal ingestion of goitrogens, such 1,9,10 1 and can breakdown T4 to T3 or to reverse T3 (rT3) which has no as rutabagas, turnips, and cabbage, during fetal development. significant biologic activity.1,8 Goitrogens interfere with iodine uptake and may therefore suppress Once in the bloodstream, over 99% of thyroid hormones are the function of the thyroid gland.1 Secondary hypothyroidism can transported by thyroxine-binding globulin (TBG), be due to pituitary or hypothalamic inflammatory or infiltrative (TTR), and albumin. Thyroid hormones are highly protein bound diseases, tumors, surgical or radiation therapy, postpartum to assure minimal urinary loss of iodide, provide uniform tissue hemorrhagic necrosis known as Sheehan’s syndrome, trauma, distribution, and transport hormones into the central nervous histiocytosis, , and autoimmune mechanisms.1,4 Other system (CNS). The unbound T4 (0.03%) and T3 (0.3%) are able than primary and secondary hypothyroidism, there is also transient to diffuse into a cell and elicit a biological effect as as elicit a hypothyroidism. Transient hypothyroidism can occur in severely response from the to release thyroid-stimulating ill patients or after excess exposure to iodine, referred to as the hormone (TSH, also known as thyrotropin).1,8,9 The Wolff-Chaikoff effect. Adaptation to the Wolff-Chaikoff effect releases TSH releasing hormone (TRH) stimulating release of typically occurs two days after iodine exposure.10 Although rare, TSH from the gland when free thyroid hormone consumptive hypothyroidism is due to excessive type III deiodinase 8,9 10 levels are low. Therefore, the production of thyroid hormones are resulting in rT3 and T3. Drugs can also cause hypothyroidism in based on a negative feedback mechanism as well as extrathyroidal persons with pre-existing thyroid abnormalities (see Table 3).1,4,9,10 deiodination of T4 and T3 dependent on nutrition, other hormones, drugs, and illness.1 When there is a dysfunction in thyroid Diagnosis production, hypothyroidism can occur. Normal levels for TSH, free Hypothyroidism has a wide range of but T , total T , and total T are listed in Table 2. 4 4 3 it is straightforward to diagnose with the proper thyroid function Hypothyroidism is more commonly due to thyroid gland tests. While signs and symptoms are no longer used exclusively failure (primary hypothyroidism) versus pituitary or hypothalamus for diagnosis, it is important to recognize these symptoms in failure (secondary hypothyroidism). Primary hypothyroidism is most commonly caused by iodine deficiency on a worldwide basis. However in areas where iodine sufficiency exists, Table 2. Normal Thyroid Hormone Levels chronic is the most common cause of TSH 0.5-4.7 mIU/L hypothyroidism.4 Chronic autoimmune thyroiditis, also known as Hashimoto’s disease, results from dysfunctional T-lymphocytes Free T4 0.8-2.7 ng/dL and excessive production of thyroid antibodies by differentiated Total T 4.5-10.9 mcg/dL B-lymphocytes that destroy thyroid cells and produce an underlying 4 defect of organobinding iodide to tyrosine. This results in Total T3 60-181 ng/dL 4 insufficient amount of active thyroid hormones. Other causes of Adapted from DiPiro JT, et al, eds. Pharmacotherapy: primary hypothyroidism include iatrogenic due to prior exposure of A Pathophysiologic Approach, 20111 radiation, , or 131I therapy; enzymatic defects within

Table 3. Drug Effects on the Thyroid4,9,11 Drug Effect , , Competitive inhibitors of iodine transport Bromine, fluorine, Block iodide transport into the thyroid Iodine, , lithium, thionamides, , cytokines Affect synthesis and secretion (poorly understood) Glucocorticoids, dopamine Interrupt hypothalamic-pituitary axis

Estrogens, heroin, methadone, mitotane, 5-fluorouracil, selective Increase T4 binding to TBG modulators, perphenazine

Androgens, anabolic steroids, glucocorticoids, nicotinic acid, Decrease binding of T4 to TBG L-asparaginase

Salicylates, furosemide, phenytoin, carbamazepine, NSAIDs (transient), Inhibit binding of T4 to TBG heparin

Barbiturates Increase thyroid hormone clearance Rifampicin, tyrosine kinase inhibitors, growth hormone, anti-thyroid Alter thyroid hormone agents ( and methimazole), beta-blockers, agents, clomipramine, phenytoin, carbamazepine

Abbreviations: T4, thyroxine, NSAID, non-steroidal anti-inflammatory drug; TBG, thyroxine binding globulin

Winter 2014: Continuing EDUCATION | www.APARX.org 3 the general hypothyroid patient. These signs and symptoms healthy patients but believe older patients, especially include: dry/cold skin, coarse hair, , cold intolerance, women, should be screened. The American Academy of Family , weakness, , , lethargy, muscle Physicians advises that patients greater than 60 years of age should stiffness, slow Achilles reflex time, , goiter, and possible be screened while the American College of Physicians believes .1 women greater than 50 years of age should be screened only if

In hypothyroidism, TSH levels and free T4 levels are used an incidental finding suggests thyroid dysfunction. The U.S. for diagnosis in most patients. The biggest exception to this is in Preventative Services Task Force and Royal College of Physicians pregnant patients, in which total serum T4 levels are recommended of London agree that screening is unjustified in healthy adults. instead of free T4 levels due to the alteration in serum proteins Because there is a lack of consensus, screening of thyroid function 1,4 during which can yield much lower values of free T4. can vary but is recommended in certain populations as seen in In order to be considered primary hypothyroidism TSH levels Table 5.4 should be higher than normal. A high TSH can be considered anything >4.5 mIU/L, however this range may differ based on Goals of Therapy institution. If a patient has a high TSH level and normal T4 Once a diagnosis of hypothyroidism has been established, level for at least four weeks, intact hypothalamic-pituitary gland, the main goals of therapy are to restore normal thyroid hormone and absence of concurrent illness, they are considered to have concentrations in the body as well as to provide symptomatic subclinical hypothyroidism.10 Overt primary hypothyroidism relief, prevent neurologic defects due to thyroid deficiency occurs when TSH is >10 mIU/L in combination with subnormal in children and newborns, and to reverse the biochemical 4 1,4,9 free T4 levels. If primary hypothyroidism is discovered, testing abnormalities associated with hypothyroidism. Once euthyroid for thyroid peroxidase antibodies (TPA) and antithyroglobulin levels are maintained in the body, symptoms such as fatigue, antibodies (TgAb) should be done to test for autoimmunity. weakness, depression, and constipation will begin to subside in Although either autoimmunity test is appropriate, TPA is more weeks; however, other clinical symptoms of hypothyroidism such specific than TgAb in assessing disease activity.9 Secondary as changes in hair and skin may take up to 6 months to resolve.9,12 hypothyroidism differs in that TSH will be normal or low in It is generally agreed that patients with TSH levels >10 mIU/L 4 combination with low free T4 levels. Patients who develop should be treated with thyroid replacement therapy; however, the secondary hypothyroidism will also show signs of pituitary benefit of treating patients with TSH levels of 4.5-10 mIU/L is insufficiency such as abnormal menses, decreased , or less certain.4 In a recent clinical trial however, even patients with evidence of a .1 Although testing and diagnosing moderate subclinical hypothyroidism (TSH 6.1-10 mIU/L) had an hypothyroidism can be simple, it can be difficult to know when to increased risk of coronary heart disease and all-cause mortality and test. may therefore benefit from thyroid supplementation.13 As of now six organizations recommend different screenings for adults for thyroid dysfunction. The American Treatment Thyroid Association recommends women and men >35 years The mainstay of treatment of hypothyroidism is thyroid old be screened every five years. The American Association of replacement therapy. This is accomplished by any of the Clinical Endocrinologist do not recommend an age to start commercially available thyroid preparations, either synthetic or natural in origin; however, is considered the drug of Table 4. Hypothyroidism Diagnosis4,9 choice in hypothyroidism, and all other formulations of thyroid hormone are not preferred.1,4,9,12 Synthetic thyroid hormone Subclinical Hypothyroidism ↑ TSH with normal T 4 preparations include levothyroxine, , and while

Overt Hypothyroidism ↑ TSH with ↓ T4 natural thyroid hormone preparations include desiccated thyroid. Alternative treatment options include the use of certain dietary Secondary Hypothyroidism Normal or ↓ TSH with ↓ T 4 supplements and nutraceuticals; however, current clinical evidence Abbreviations: ↑, increase; ↓, decrease; does not support their use.4 TSH, thyroid stimulating hormone; T4, thyroxine

Table 5. Recommended Thyroid Screening4,9 Populations to Support Thyroid Level Testing • Adrenal insufficiency • • Unspecified myopathy • Alopecia • Type I diabetes mellitus • Prolonged QT interval • Anemia • Dysmenorrhea • Vitiligo • Cardiac dysrhythmia • • Weight gain • Changes in skin texture • Hypertension • Goiter • Congestive • Mixed • Slowed ankle-reflex relaxation time • Constipation • Malaise/fatigue

4 Alabama pharmacy ASSOCIATION | WINTER 2014: Continuing EDUCATION Levothyroxine (Levothroid®, Levoxyl®, Synthroid®) is the drug Food, as well as certain , reduces the absorption of of choice for thyroid replacement because it is free of antigenicity, levothyroxine (see Table 6). Levothyroxine should be administered relatively inexpensive, chemically stable, and has uniform potency. in the morning, at least 30 minutes before food in order to

It is a synthetic form of the T4 hormone, and although T3 is the minimize the chance of any interference with absorption. biologically more active form of thyroid hormone, levothyroxine is Liothyronine (Cytomel®) is a chemically pure synthetic form 1,4,9 consistently and readily converted to T3 in the body. Dosing for of T3. It is an option for thyroid replacement in hypothyroidism; levothyroxine for full thyroid replacement is approximately 1.6 to however, it is not first line therapy. While T3 is four times more

1.7 mcg/kg daily in otherwise healthy adults; however, in patients potent than T4 due to increased receptor affinity, there is no clear with subclinical hypothyroidism, doses of only 25-75 mcg/day advantage for using liothyronine over levothyroxine because T4 is 1,9 may be necessary to achieve euthyroid levels. Age and comorbid rapidly and readily converted to T3 in the body. Disadvantages conditions also affect levothyroxine dosing. For example, of liothyronine use include a higher incidence of cardiac adverse patients >50 years old with cardiac disease should be started at effects, higher cost, and difficulty in monitoring with conventional 1,12,14-16 lower doses (12.5-50 mcg/day) compared to otherwise healthy laboratory tests such as free T4. Liothyronine also has a adults (approximately 125 mcg/day). Repeat TSH tests should relatively short half-life (1.5 days) and is rapidly absorbed, resulting guide therapy adjustments for all patients; levothyroxine should in wide fluctuations in serum T3 levels. The use of liothyronine as be adjusted by approximately 12-25 mcg every 4-8 weeks until monotherapy is reserved for use as a second-line drug with specific euthyroid levels are achieved.1,4,9,14-16 Due to potential variations in indications such as coma.1,9,12 If liothyronine is used the various tablet formulations and due to concerns of uncertainty to treat general hypothyroidism, doses typically are initiated at 25 about the Food and Drug Administration’s method for determining mcg/day and increased by 12.5-25 mcg/day every 1-2 weeks to a bioequivalence of thyroxine preparations, it is recommended maximum of 100 mcg/day. A usual maintenance dose is between as best practice that once a patient is started on one brand of 25-75 mcg/day.14-16 levothyroxine , he/she should remain on that same Liotrix (Thyrolar®) is a synthetic combination of T4 and T3 product in order to minimize variability from refill to refill.4,17 in a 4:1 ratio that attempts to mimic natural hormone secretion. Levothyroxine is generally well tolerated if dosing is While it does have a predictable potency, the major limitations of appropriate to achieve and maintain euthyroid levels. Adverse liotrix include high cost, increased incidence of cardiotoxicity, and 1,4 reactions are primarily signs of due to therapeutic lack of therapeutic rationale since most T3 is converted from T4. overdosing of levothyroxine. These adverse effects include Many clinical trials comparing T4 with combinations of T4 and palpitations, tachycardia, arrhythmias, hyperactivity/insomnia, T3 have shown, in general, combination therapy is no better than , irritability, alopecia, decreased bone mineral density, levothyroxine alone. Some patients, however, prefer combination excessive sweating, diarrhea, and elevations in . therapy over levothyroxine monotherapy. This preference may Weight loss is also a common side effect; however, levothyroxine, come from patients with different genetic subtypes of type II as well as all thyroid hormone products, contains a black box deiodinase. In a large-scale study comparing levothyroxine warning that these products should not be used alone or with other monotherapy versus combination levothyroxine and liothyronine therapeutic agents for the treatment of or weight loss due therapy, a more favorable response was seen on the General Health to potential life-threatening toxicities (heart failure, myocardial Questionnaire in patients on combination therapy who had this infarction) associated with the larger than normal doses needed for altered type II deiodinase subtype; however no difference in serum weight loss.14-16 Allergic or idiosyncratic reactions are extremely rare thyroid hormone levels was found.18 While these results require with levothyroxine due to its synthetic origin; however, Synthroid® replication, it may suggest a future role in genotyping to determine 50 mcg tablets are considered to be the least allergenic of all the appropriate type of hypothyroidism replacement therapy.4,10 If levothyroxine preparations due to a lack of dye and few excipients liotrix is to be used for treatment of hypothyroidism, initial dosing and should be tried when an allergy is suspected.1 is 25 mcg/6.25 mcg of levothyroxine and liothyronine, respectively, once daily. Doses may be increased by 12.5 mcg/3.1 mcg every 2-3 weeks. The usual maintenance dose is 50-100 mcg/12.5-25 Table 6. Food and Medications that Reduce mcg daily.14-16 Levothyroxine Absorption1,4,9 Natural thyroid hormone products, or desiccated thyroid Food Medication (Armour Thyroid®, Nature-Thyroid®), are derived from hog, • Grapefruit juice • Bile acid sequestrants beef, or sheep thyroid gland. Although desiccated thyroid is • Coffee • Sucralfate inexpensive, as an animal protein-derived product it may be • Foods high in fiber • Ferrous Sulfate antigenic in allergic or sensitive patients, leading to hypersensitivity • Soy • Phosphate binders reactions.1,4 There is no clinical advantage or evidence to support • Calcium using desiccated thyroid over levothyroxine monotherapy and • Ciprofloxacin therefore, desiccated thyroid hormone should not be used in the • Bisphosphonates treatment of hypothyroidism.4 • Histamine blockers • Proton pump inhibitors

Winter 2014: Continuing EDUCATION | www.APARX.org 5 Table 5. Summary of Available Thyroid Preparations1,4,9 Drug Name Form Cost Adverse Effects Other Comments

st Levothyroxine Synthetic T4 Inexpensive s/s of hyperthyroidism 1 line therapy

Liothyronine Synthetic T3 Expensive s/s of hyperthyroidism; Difficult to monitor with Increased CV adverse effects standard testing Liotrix Synthetic Combination Expensive s/s of hyperthyroidism; Possibly preferred in patients

T4:T3 (4:1) Increased CV adverse effects with altered subtypes of type II deiodinase

Desiccated thyroid Natural T4:T3 (4.2:1) Inexpensive s/s of hyperthyroidism; Antigenic; should not be used Hypersensitivity reactions

Abbreviations: T4, thyroxine; T3, triiodothyronine; s/s, signs and symptoms; CV, cardiovascular Alternative Therapies not recommended by guidelines; however, it is important that Alternative therapies that have been suggested to play a role in healthcare professionals are aware that these supplements may the treatment of hypothyroidism include dietary supplements and contain significant amounts of thyroid hormone.4 nutraceuticals; however, the majority of these supplements fail to has been investigated as a modulator of autoimmune meet a level of scientific substantiation deemed necessary for the due to the fact that various selenoenzymes are treatment of disease.4 The dietary supplements and nutraceuticals found in many antioxidant, oxidation-reduction, and thyroid that have been hypothesized to have a role in treating hormone deiodination pathways.4 In various clinical trials, hypothyroidism include 3,5,3’-triiodothyroacetic acid (TRIAC, results over the benefit of selenium have been conflicting. More ), thyroid-enhancing preparations, and selenium. Other recently, a systematic review and meta-analysis of prospective supplements with thyromimetic properties include Asian ginseng, studies involving patients with Hashimoto’s disease receiving bladderwrack, capsaicin, echinacea, and forskolin; however, while levothyroxine therapy, supplementation with selenium resulted these supplements have been studied, they are of unproven clinical in a decrease in thyroid peroxidase (TPOab) titers benefit.4 as well as an improved mood and general well-being; however,

TRIAC is an active metabolite of T3 which has been sold there were no changes in ultrasonographic thyroid morphology over-the-counter for weight loss. It appears to have enhanced or levothyroxine doses. The authors concluded that before hepatic and skeletal thyromimetic effects as compared to selenium supplementation should be routinely recommended in levothyroxine; however, the FDA has issued a warning against its the treatment of autoimmune thyroiditis, improvement in thyroid use due to lack of proven benefit as well as serious side effects and function and morphology should be demonstrated.21 Current health consequences, including heart attack and stroke.4,19 It is guidelines state that selenium should not be used to prevent or no longer available in the United States or Canada due to these treat hypothyroidism, and while there is a theoretical potential potential risks. for selenium to have beneficial effects on hypothyroidism, at the Various preparations marketed as “thyroid-enhancing” or present time there is not enough outcome data to support its use.4 “thyroid support” are available over-the-counter. L-tyrosine, B vitamins, garlic, ginger, ginkgo, licorice, magnesium, manganese, Prognosis meadowsweet, oats, pineapple, potassium, saw palmetto, and Treated properly, patients with hypothyroidism can live valerian are all ingredients that are commonly included in these productive, generally symptom-free lives; however, hypothyroidism products. L-tyrosine has been speculated to have a role in the is a chronic condition and therapy with thyroid supplementation treatment of hypothyroidism due to its role in thyroid hormone is generally life-long.22 Uncorrected hypothyroidism can synthesis; however, there are no preclinical or clinical studies cause several complications such as psychiatric impairment, demonstrating any thyromimetic properties for L-tyrosine or cardiovascular abnormalities, , hypercholesterolemia, any of the other ingredients included in these various thyroid and increased risk of . In a recent study of adult preparations.4 In a recent study, 9 out of 10 over-the-counter Taiwanese patients, subclinical hypothyroidism was found to thyroid support supplements contained a clinically significant be independently associated with an increased risk of all-cause 23 amount of T3 (>10 mcg/day) and T4 (>90 mcg/day). The authors mortality as well as cardiovascular disease mortality. Untreated concluded that the majority of dietary thyroid supplements studied overt hypothyroidism may cause other devastating comorbid do indeed contain significant amounts of thyroid hormone, conditions such as , heart failure, and , potentially exposing patients to an increased risk of altering his/ which has a mortality rate of up to 70%.1,3,9 her thyroid levels even to the point of developing iatrogenic Treatment of hypothyroidism, even subclinical, is thyrotoxicosis.20 The use of thyroid-enhancing supplements is particularly important during pregnancy due to an increased

6 Alabama pharmacy ASSOCIATION | WINTER 2014: Continuing EDUCATION risk of , preterm delivery, preeclampsia, and maternal Conclusion hypertension if the mother is not treated.24 These risks from Hypothyroidism is a life-long condition due to the failure maternal hypothyroidism have been shown to be associated of the thyroid gland to produce sufficient thyroid hormone with an increased admission to the neonatal to maintain normal body function, often caused by chronic (NICU).25 Thyroid hormone is necessary for fetal growth and must autoimmune disorders such as Hashimoto’s thyroiditis.1,4,9 be supplied by the mother for the first two months of gestation.1,9 Thyroid function is needed for normal growth and development Congenital hypothyroidism may lead to irreversible mental and in children and for metabolic stability in organ functions for physical impairment, retarded myelination of nerve fibers, and adults. Fortunately, it is very treatable and when treated properly, reduced vascularity; therefore, treatment should begin as soon primarily with levothyroxine, hypothyroidism has a good as possible in the infant, but at least within 45 days to minimize prognosis. Left untreated, it can lead to many complications these risks.1,26 including neurologic complications, cardiac abnormalities, hypercholesterolemia, coma, and even death.1,3,9 Routine follow-up Risk Reduction of symptoms and laboratory values is necessary to ensure patients’ While the development of hypothyroidism may be due to clinical stability as well as to decrease future complications. varying etiologies, there are some specific steps that a patient can take to help reduce his/her risk of developing hypothyroidism or causing additional destruction to the thyroid. Smoking cessation may play a role in reducing the risk for thyroid disorders. Thiocyanate, a major component of tobacco, can have an impact on thyroid function. Thiocyanate inhibits thyroid hormone synthesis and iodine uptake in the body. In addition, the thyroid can be affected through smoking-induced sympathetic stimulation; however, smoking effect on the thyroid, specifically, remains inconclusive and contradictory.27 Another method of risk reduction is the use of a thyroid collar during routine x-rays. This additional protection helps to shield the thyroid from unwanted radiation.28

REFERENCES 1. 1. Jonklaas J, Talbert RL. Thyroid disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, BG, Posey LM, editors. Pharmaco- therapy: A pathophysiologic approach. 8th ed. New York: McGraw-Hill Medical; c2011. p. 1303-1326. 2. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002 Feb;87(2):489-499. 3. Hinton CF, Harris KB, Borgfeld L, Drummond-Borg M, Eaton R, Lorey F, Therrell BL, Wallace J, Pass KA. Trends in incidence rates of congenital hypothyroidism related to select demographic factors: data from the United States, California, , New York, and . Pediatrics. 2010;125(2):37-47. 4. Garber JR, Cobin RH, Gharib H, et al; American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):989-1028. 5. Potlukova E, Potluka O, Jiskra J, Limanova Z, Telicka Z, Bartakova J, Springer D. Is age a risk factor for hypothyroidism in pregnancy: an analysis of 5223 pregnant women. J Clin Endocrinol Metab [Internet]. 2012 Jun 1 [cited 2014 Jan 27];97(6):1945-1952. Available from: http://press.endocrine.org/doi/pdf/10.1210/jc.2011-3275. 6. Al-Geffari M, Ahmad NA, Al-Sharqawi AH, Youssef AM, AkNaqeb D, Al-Rubeaan K. Risk factors for thyroid dysfunction among type 2 diabetic patients in a highly diabetes mellitus prevalent society. Int J Endocrinol [Internet]. 2013 Dec 1 [cited 2014 Jan 27]; 2013:1-6. Available from: http://www.hindawi.com/journals/ije/2013/417920/. 7. Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Increased pregnancy loss rate in thyroid antibody nega- tive women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab. 2010;95:E44-48. 8. How your thyroid works: a delicate feedback mechanism [Internet]. Montclair (NJ): Vertical Health LLC; [updated 2012 Jan 30; cited 2014 Jan 28]. Available from: http://www.endocrineweb.com/conditions/thyroid/how-your-thyroid-works. 9. Dong BJ, Schneider EF. Thyroid disorder. In: Alldredge BK, Corelli RL, Ernst ME, Guglielmo BJ, Jacobson PA, Kradjan WA, Williams BR, editors. Koda-Kimble & Young’s applied therapeutics. 10th ed. Philadelphia: Wolters Kluwer Health; c2013. p. 1187-1222.

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