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Clinical Review Hypothyroidism and Subclinical Hypothyroidism in the Older Patient Samuel L. Gurevitz, Jennifer A. Snyder, Katie L. Peterson, Kristin L. Kelly Objective: To review the etiology, precipitating factors, clinical findings, screening recommendations, and treatment for primary hypothyroidism and subclinical hypothyroidism in the older patient. Data Sources: A PubMed search of English language articles using a combination of words: elderly, thyroid, hypothyroid,* subclinical hypothyroid,* etiology, screening, diagnosis, and treatment to identify original studies, guidelines, and reviews on primary hypothyroidism and subclinical hypothyroidism published between 1979 and present. Study Selection and Data Extraction: Overall, 51 clinical reviews, original studies, references, and guidelines were obtained and evaluated on their clinical relevance to the older patient population. Data Synthesis: The literature included guidelines and considerations for the diagnosis, screening, and management of subclinical and overt primary hypothyroidism in the older patient. Conclusion: Females and individuals 60 years of age or older have a higher prevalence of primary hypothyroidism and subclinical hypothyroidism. While screening recommendations exist, the need or suggested age to initiate screening varies among organizations. TSH and free T4 values are used for diagnosing and monitoring. Levothyroxine remains the drug of choice for replacing endogenous thyroid hormone. Despite evidence to suggest its need, the treatment of subclinical hypothyroidism remains controversial. Key Words: Elderly, Geriatrics, Hypothyroidism, Screening, Subclinical hypothyroidism, Treatment. Abbreviations: AACE = American Association of Clinical Endocrinologists, ATA = American Thyroid Association, NTI = Narrow therapeutic index, T3 = Triiodothyronine, T4 = Thyroxine, TBG = Thyroxine-binding globulin, TPO = Thyroid peroxidase, TRH = Thyrotropin-releasing hormone, TSH = Thyroid-stimulating hormone. Consult Pharm 2011;26:000-00. Introduction Primary hypothyroidism, or insufficiency of the thyroid leading to a reduction in thyroid hormones thyroxine (T4) and triiodothyronine (T3), is a common disorder affecting 1% to 10% of the U. S. population.1-4 It is more often found in females and has a higher prevalence in those 60 years of age or older. Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level associated with normal total or free T4 and T3 levels.5 Subclinical hypothyroidism is also more common in white females and is on the rise in the United States with a variable reported prevalence rate of 4% to 20%.1,2,4-6 According to the American Association of Clinical Endocrinologists’ (AACE) guidelines regarding thyroid dysfunction, subclinical hypothyroidism affects up to 20% of persons older than 60 years of age.7 In long-term care facilities, undiagnosed hypothyroidism can be found as frequently as one in every four residents.8,9 As a large portion of the U. S. population continues to age, clinicians are likely to see an increased incidence of hypothyroid and subclinical hypothyroid disorders. This review will summarize the etiology, precipitating factors, clinical findings, screening recommendations, and treatment for hypothyroidism and subclinical hypothyroidism in the older patient. Etiology The thyroid gland is located immediately below the larynx and anterior to the trachea and is responsible for secreting the thyroid hormones T4 and T3. The secretion of thyroid hormones is initiated by thyrotropin-releasing hormone (TRH), released from the hypothalamus.10 TRH stimulates the anterior pituitary to secrete TSH.11 Available data conclude no change occurs in the TSH response to TRH with aging.12 TSH then causes thyroperoxidase to liberate iodine and allow the coupling of iodine and tyrosine in specific regions of thyroglobulin molecules.13,14 This leads to the synthesis of T4 and T3. These hormones are then secreted from the thyroid. In elderly patients, thyroid secretion and degradation is reduced, leading to unchanged serum T4.15 The secretion of TRH and TSH is regulated by feedback inhibition of T4 and T3.11 The most biologically active thyroid The Consultant Pharmacist SEPTEMBER 2011 Vol. 26, No. 9 657 Clinical Review Table 1. Daily Recommended Iodine Levels mcg/day Table 2. Medications That May Induce Hypothyroidism or Alter the Effects of Levothyroxine Infant (under 1 year) 50 Children, 2-6 years of age 90 Induce hypothyroidism by inhibiting thyroid hormone Children, 7-12 years of age 120 production and/or release Beyond 12 years of age–adults, 150 Aminogluthimide including elderly Pregnant and lactating women Amiodarone 200 Source: Reference 24. Interferon-α Iodine Lithium hormone is T3; however, it is secreted by the thyroid in a lesser amount than T4. The majority of T3 is produced by peripheral conversion of T4 by the enzymes T4-5’deiodinases, which selectively remove iodine from T4.16,17 Hypothyroidism can be divided into three major categories: primary, secondary, and tertiary.18 Primary hypothyroidism is an insufficiency of thyroid hormone specifically as a result of dysfunction of the thyroid. Secondary and tertiary hypothyroidism are caused by pathologies associated with pituitary gland and hypothalamus dysfunction, respectively. This review will focus specifically on primary hypothyroidism. The causes of both overt and subclinical primary hypothyroidism include processes such as autoimmune destruction, substrate deficiency or excess, enzymatic dysfunction, and iatrogenic etiologies. According to AACE, the most common cause of primary hypothyroidism in the United States, including the elderly population, is Hashimoto’s thyroiditis.7 It is a chronic autoimmune destruction of the thyroid gland resulting in the inhibition of the action of TSH through thyroperoxidase and thyrogobulin antibodies or TSH receptor antibodies.7,19 This blockade results in damage and eventually atrophy of the thyroid gland.20 Hashimoto’s thyroiditis expresses a genetic component, showing familial clustering and a higher incidence in monozygotic twins than in dizygotic twins, as well as in some cases expressing the human leukocyte antigen types.21 The disease also has a predilection for Caucasians with a lower incidence in Japanese- and African-Americans.19 658 Perchlorate Thionamides Interfere with levothyroxine absorption Antacids containing aluminum hydroxide Calcium carbonate Cholestyramine Colesevalam Ferrous sulfate Lanthanum Proton pump inhibitors Raloxifene Sevelamer Sucralfate Alter levothyroxine metabolism leading to increasing dosage requirements Amiodarone Carbamazepine Estrogen Phenytoin Rifampin Source: References 19, 25, 26, 41, 48. The Consultant Pharmacist SEPTEMBER 2011 Vol. 26, No. 9 Clinical Review Table 3. Symptoms and Signs of Hypothyroidism Arthralgias and/or myalgias Ataxia Bradycardia Coarseness or loss of hair Cold intolerance Constipation requirements for iodine, and the level is age dependent (Table 1).24 Additional causes of hypothyroidism include thyroid atrophy and fibrosis associated with the normal aging process, thyroid surgery that is often associated with thyroid cancer or Graves’ disease, and high doses of radioiodine therapy that result in thyroid gland destruction.25 Several medications are known to cause drug-induced hypothyroidism (Table 2); therefore, with their use, periodic monitoring of TSH is suggested.25,26 Decreased concentration Delayed deep tendon reflexes Depression Dry and/or yellow skin Dyspnea Fatigue Goiter Hoarseness Hyperlipidemia Hypothermia Infertility Irregular or heavy menses Memory and mental impairment Myxedema fluid infiltration of tissues Weakness Weight gain Source: References 6,9,16. Other etiologies of hypothyroidism include both excessive iodine intake and severe iodine deficiency.14 Excessive amounts of iodine, from 500 to 1,000 µ/ day, cause suppression of thyroid function. This results in decreased thyroid hormone production. Severe iodine deficiency directly suppresses the production of T4 hormone by limiting the “building blocks” for T4 production.19 Furthermore, a drastic fluctuation in the amount of iodine consumed can greatly impact the formation of thyroid hormones.22,23 The World Health Organization establishes the recommended daily Clinical Findings While subclinical hypothyroidism may be asymptomatic, there are a range of symptoms and signs associated with both overt and subclinical hypothyroidism (Table 3).6,15,19 Signs and symptoms of hypothyroidism and subclinical hypothyroidism may go unrecognized in the elderly population as a result of subtle clinical manifestations that may be misinterpreted as normal characteristics of aging (e.g., cognitive impairment, constipation).27 Additionally, chronic disease states and other comorbid conditions may mask findings of hypothyroidism and make the diagnosis difficult.15,25 Hypothyroidism, if left untreated, may increase the risk of hyperlipidemia, cardiac dysfunction, or cognitive impairment. Hypothyroidism is a risk factor for statininduced myopathy.28 Subclinical hypothyroidism may progress to overt hypothyroidism.6,7 New evidence suggests that subclinical hypothyroidism leads to increased levels of homocysteine, which is an independent risk factor for atherosclerotic heart disease.29 A recent cohort study of elderly adults determined that men with subclinical hypothyroidism have an increased risk of developing a hip fracture.30 Screening and Diagnosis Given the many comorbidities and complications associated with overt and subclinical hypothyroidism, screening the elderly population for thyroid disease may be worthwhile in decreasing morbidity and mortality; however, large-scale studies are needed.31 While the U. S. Preventive Services Task Force concludes there is insufficient evidence to screen the general patient population The Consultant Pharmacist SEPTEMBER 2011 Vol. 26, No. 9 659 Clinical Review Table 4. Screening Guidelines for Thyroid Disease Table 5. Normal Adult Thyroid Function Panel Values American Thyroid Adults should be screened Association beginning at age 35 years and at intervals every 5 years thereafter. LabNormal Range Thyroid-stimulating hormone 0.4-4.2 mIU/L Total T4 5.4-11.5 mcg/dL United States Preventive There is insufficient evidence Free T4 0.7-2.0 ng/dL Services Task Force to screen the general patient Thyroperoxidase antibodies Negative population for thyroid Source: Reference 36. disease. American College of Screening women older than Physicians 50 years may be indicated. American Academy of Recommends against routine Family Physicians screening for thyroid disease in patients younger than 60. Source: References 32-35. for thyroid disease, there are other national organizations that do recommend screening (Table 4).32-35 If a patient has nonspecific symptoms or signs that can be attributable to thyroid dysfunction, thyroid function tests should be ordered. The single most useful test to screen for thyroid dysfunction is the sensitive TSH assay.7 An elevated TSH assay helps to establish the diagnosis of hypothyroidism in primary thyroid disease (Table 5).36 If TSH is elevated, a total T4 should be ordered to determine the functioning status of the thyroid. In primary hypothyroidism, T4 levels are decreased. T4 levels are highly bound to proteins (thyroxine-binding globulin [TBG], albumin, and transthyretin) and may be abnormal as a result of medication usage.19 The most common cause of hypothyroidism in a euthyroid elderly subject is lithium, estrogen, cytokine, or amiodarone therapy, whereas low T4 is seen during therapy with carbamazepine and similar drugs.19 Total T4 may be adjusted to obtain a ‘free T4 estimate’ using the T3 test or by measuring TBG and adjusting for TBG abnormalities. Hypothalamic and pituitary dysfunction can lead to normal TSH levels and yet abnormal 660 thyroid hormone levels; therefore, a T4 level should be included if overt hypothyroidism symptoms and signs are present.19 TSH levels have a narrow normal range. According to a 20-year longitudinal study performed by Vanderpump utilizing the Whickham Survey, 1,700 subjects demonstrated a higher prevalence of progression to overt thyroid disease when their TSH level was greater than 2 mIU/L.37 The risk was much higher in individuals also positive for antithyroid antibodies at baseline testing. If patients have an upper level normal reference range TSH, they should be retested in 3 to 6 months to determine if there is a change in their status, especially if they have positive antithyroid peroxidase antibodies.38 Serum T3 is not a sensitive marker of thyroid hypofunction. Serum T3 tends to remain normal until severe hypothyroidism develops. This is probably caused by a combination of enhanced T3 synthesis in the stimulated thyroid and enhanced T4 deiodination to T3 catalyzed by deiodinase type 2.19 On the other hand, severe disease, starvation, and many drugs lead to a low serum T3 not caused by hypothyroidism. In a study by Iglesias et al., the reduction of free T3 values, found in about two thirds of the patients, was a powerful predictor for mortality during hospitalization in elderly patients.2 The most common supplementary test to evaluate involvement of autoimmunity is thyroid peroxidase (TPO) antibodies in serum. In patients with subclinical hypothyroidism, the presence of TPO The Consultant Pharmacist SEPTEMBER 2011 Vol. 26, No. 9 Clinical Review antibodies indicates enhanced risk of progression of thyroid insufficiency. Treatment The treatment goals for hypothyroidism are to replace the missing hormones, relieve symptoms, and reverse the biochemical abnormalities of hypothyroidism as evidenced by normal blood levels of TSH and free T4. Thyroid hormone is administered to supplement or replace endogenous production. According to the AACE, treatment is indicated in patients with TSH levels > 10 μIU/mL or in patients with TSH levels between 4.5 and 10 μIU/mL in conjunction with goiter or positive antithyroid peroxidase antibodies (or both).5 In the United States, there are several thyroid hormone preparations currently available. They include levothyroxine sodium (thyroxine), liothyronine (triiodothyronine), and desiccated thyroid (contains thyroxine and liothyronine), as well as a synthetic combination of levothyroxine sodium and liothyronine (liotrix). Desiccated thyroid extract is derived from the porcine thyroid gland, which contains both thyroxine and liothyronine in a ratio of 1:4.22. Liotrix is a synthetic combination with a fixed dose of thyroxine and liothyronine (1:4 ratio). Liothyronine (T3) is a synthetic version of the thyroid hormone. It has a shorter half-life (1.5 days) compared with T4 (7 days). Liothyronine has no role in the treatment of primary hypothyroidism.39 The approximate equivalent doses for different thyroid supplements are: thyroid (porcine) 1 grain (60 mg) = 1 tablet of liotrix = 25 mcg of liothyronine = 100 mcg of levothyroxine.40 According to the AACE and the American Thyroid Association (ATA), levothyroxine is the treatment of choice for hypothyroidism.7,41 Once absorbed, levothyroxine is converted to T3.There is insufficient evidence regarding the treatment with a combination of thyroxine and liothyronine. A meta-analysis comparing thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for treatment of hypothyroidism found no difference in the effectiveness of the combination versus the monotherapy.42 Hypothyroidism develops over a prolonged period of time, and correction should be made slowly. Although the appropriate dosage may vary among patients, the average levothyroxine replacement dose to normalize TSH in most patients is 1.6 to 1.7 mcg/kg/day.19,43 In older patients the requirement falls to 1 mcg/kg/day or less.41,43 Alternatively, elderly patients and those with known cardiovascular disease, should have levothyroxine initiated at 12.5 mcg to 25 mcg per day. This should be titrated upward in increments of 25 mcg until TSH is normalized based on subsequent measurements obtained every 4 to 6 weeks.25,44,45 The goal TSH is between 0.3 and 3 µIU/mL.7 Once the TSH is stable on a maintenance dose, follow-up monitoring in older adults should be every 6 to 12 months.19,25 Levothyroxine is recognized as a drug with a narrow therapeutic index (NTI), and its dose is adjusted to keep TSH within the desired range. It is important to recognize factors that may interfere with the ability to maintain a desired TSH concentration. Food can diminish the absorption by 40% to 64%.46 It is recommended that levothyroxine be administered while fasting, usually one hour before meals. Recently a randomized, doubleblind, crossover trial concluded levothyroxine taken at bedtime significantly improved thyroid hormone levels.47 In addition, many older adults have multiple comorbidities and are more likely to be affected by the risks of polypharmacy. Polypharmacy increases the risk of interactive effects of medications. There are several medications that interfere with the absorption of levothyroxine (Table 2).19,25,26,41,48 To alleviate this potential, levothyroxine administration should be spaced at least 4 hours apart from these medications.41 Other drugs can accelerate the metabolism of levothyroxine that may lead to an increase in levothyroxine dosage (Table 2).19,26 Additional factors that may alter levothyroxine requirements are malabsorptive diseases, like celiac disease.48 Because levothyroxine has an NTI, the potential for insufficient treatment or overtreatment (iatrogenic hyperthyroidism) must be recognized. Adverse effects related to overtreatment include nervousness, difficulty concentrating, palpitations, tremor, or chest pain. The patient should be evaluated, and if excess T4 is confirmed, the current dose should be withheld for a week and then restarted at The Consultant Pharmacist SEPTEMBER 2011 Vol. 26, No. 9 661 Clinical Review a lower dose. Some patients remain asymptomatic even though T4 is elevated. A reduced bone mineral content has been associated with over-replacement of levothyroxine. It is recommended that these patients have their dose reduced.19,41 Bioequivalence of levothyroxine preparations is a significant issue. Because differences may exist among the preparations, The Endocrine Society is concerned with interchangeability of levothyroxine preparations. Changing a patient to a new levothyroxine preparation could lead to over- or undertreatment with possible adverse effects.49,50 In a study conducted by The Endocrine Society, AACE, and the ATA, switching patients to other levothyroxine products without the knowledge of the physician resulted in 160 adverse events.50 If the brand of levothyroxine is switched, the patient and physician should be informed, and the patient’s TSH should be retested in six weeks. Open communication with the prescribing health care practitioner is highly recommended. The pharmacist should educate the patient that switching formulations, particularly multiple times, may lead to increased medical costs in terms of follow-up care and unwanted adverse effects. Significant controversy persists regarding the treatment of patients with subclinical hypothyroidism. Most professional organizations and evidence-based guidelines advocate starting replacement therapy in elderly patients who have TSH concentrations greater than 10 mIU/L and in those with antithyroid antibodies, and in symptomatic elderly patients with TSH levels between 4.5 and 10 mIU/L.38,43 When the decision is made to start treatment, the initial dose should not exceed 25 mcg per day and the dose should be increased slowly to avoid precipitating coronary symptoms. Follow-up of TSH measurement should be repeated in 6 to 8 weeks.51 The target TSH in the elderly is also controversial. The current available data suggest that, in individuals older than 70 years of age, it is reasonable to initiate levothyroxine with the goal of a TSH level between 4 and 6 mlU/L. Treatment of subclinical hypothyroidism should probably be avoided in patients older than 85 years of age with a TSH level between 4.5 and 10 mIU/L.38,51 Prospective therapeutic trials are necessary to clarify the 662 necessity of replacement therapy in the elderly. Role of the Pharmacist How can pharmacists incorporate the guidelines for hypothyroidism into their daily practice? • Review the patient’s medications that may cause hypothyroidism or for drug interactions. • Monitor for signs and symptoms for hypothyroidism. • Confirm and make recommendations to ensure thyroid hormones are administered correctly in regard to meals and other medications. • Monitor for adverse reactions and therapeutic response (signs and symptoms and TSH goal). • Recommend patients older than 60 years of age be screened for hypothyroidism. • Assess older patients for hypothyroidism and, if necessary, treat to attain a euthyroid state before starting statin therapy. • Initiate low-dose levothyroxine (12.5-25 mcg per day) in those older than 60 years of age and patients with ischemic heart disease. This should be titrated upward in increments of 25 mcg until TSH is normalized based on subsequent measurements obtained every 4 to 6 weeks. • Retest TSH levels in six weeks if the brand of levothyroxine is switched. Conclusion Primary hypothyroidism is defined as an elevated TSH and a decrease in thyroid hormones; whereas, subclinical hypothyroidism is an elevated TSH associated with normal thyroid hormones. Patient presentation and physical exam findings range from asymptomatic to severe. Screening recommendations are divisive and vary among organizations. Levothyroxine remains the treatment of choice. Treatment is indicated in patients with TSH levels > 10 μIU/mL or in patients with TSH levels between 4.5 and 10 μIU/mL in conjunction with goiter or positive anti-TPO antibodies (or both). Despite evidence to suggest its need, the treatment of subclinical hypothyroidism remains controversial. TSH levels should be monitored regularly to ensure adequate supplementation. The Consultant Pharmacist SEPTEMBER 2011 Vol. 26, No. 9 Clinical Review Samuel L. Gurevitz, PharmD, CGP, is assistant professor, Physician Assistant Program, College of Pharmacy and Health Sciences, Butler University, Indianapolis, Indiana. Jennifer A. Snyder, MPAS, PA-C, DFAAPA, is associate professor, Physician Assistant Program, College of Pharmacy and Health Sciences, Butler University, Indianapolis. Katie L. Peterson, ATC, PA-S, is physician assistant student, Physician Assistant Program, College of Pharmacy and Health Sciences, Butler University, Indianapolis. Kristin L. Kelly, PA-S, is physician assistant student, Physician Assistant Program, College of Pharmacy and Health Sciences, Butler University, Indianapolis. For correspondence: Samuel L. Gurevitz, PharmD, CGP, Physician Assistant Program, College of Pharmacy and Health Sciences, Butler University, 4600 Sunset Avenue, Indianapolis, IN 46208. Tel: (317) 940-6542; Fax: (317) 940-6172; E-mail: sgurevit@butler. edu. Disclosures: No funding was received for this study or the development of the manuscript. The authors report no potential conflicts of interest. © 2011 American Society of Consultant Pharmacists, Inc. All rights reserved. Doi:10.4140/TCP.n.2011.000. References 1. Hollowell JG, Staehling NW, Flanders WD et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489-99. 2. Iglesias P, Munoz A, Prado F et al. Alterations in thyroid function tests in aged hospitalized patients: prevalence, aetiology, and clinical outcome. Clin Endocrinol 2009;70:961-7. 3. Cooper DS. Clinical practice. Subclinical hypothyroidism. N Engl J Med 2001;345:260-5. 4. Aoki Y, Belin RM, Clickner R et al. Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002). Thyroid 2007;17:1211-23. 5. Gharib H, Tuttle RM, Baskin HJ et al. Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. J Clin Endocrinol Metab 2005;90:581-5. 6. Jones DD, May KE, Geraci SA. Subclinical thyroid disease. Am J Med 2010;123:502-4. 7. Baskin HJ, Cobin RH, Duick DS et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002;8:457-69. 8. Thong H, Rahimi AR. Prevalence of hypothyroidism in a southeastern nursing home. J Am Med Dir Assoc 2000;1:25-8. 9. Drinka PJ, Nolten WE, Voeks SK et al. Follow-up of mild hypothyroidism in a nursing home. J Am Geriatr Soc 1991;39:264-6. 10. Monga V, Meena CL, Kaur N et al. Chemistry and biology of thyrotropin-releasing hormone (TRH) and its analogs. Curr Med Chem 2008;15:2718-33. 11. Nillni EA. Regulation of the hypothalamic thyrotropin releasing hormone (TRH) neuron by neuronal and peripheral inputs. Front Neuroendocrinol 2010;31:134-56. 12. Felicetta JV. Thyroid changes with aging: significance and management. Geriatrics 1987;42:86-8, 91-2. 13. Ruf J, Carayon P. Structural and functional aspects of thyroid peroxidase. Arch Biochem Biophys 2006;445:269-77. 14. Triggiani V, Tafaro E, Giagulli VA et al. Role of iodine, selenium, and other micronutrients in thyroid function and disorders. Endocr Metab Immune Disord Drug Targets 2009;9:277-94. 15. Mariotti S, Franceschi C, Cossarizza A et al. The aging thyroid. Endocr Rev 1995;16:686-715. 16. Gereben B, Zavacki AM, Ribich S et al. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev 2008;29:898-938. 17. Hall JA, Bianco AC. Triumphs of the thyroid despite lesser conversion. Endocrinology 2009;150:2502-4. 18. Roberts CG, Ladenson PW. Hypothyroidism. Lancet 2004; 363:793-803. 19. Laurberg P, Andersen S, Bulow Pedersen I et al. Hypothyroidism in the elderly: pathophysiology, diagnosis and treatment. Drug Aging 2005;22:23-38. The Consultant Pharmacist SEPTEMBER 2011 Vol. 26, No. 9 663 Clinical Review 20. Umar H, Muallima N, Adam JM et al. Hashimoto’s thyroiditis following Graves’ disease. Acta Med Indones 2010;42:31-5. 21. Hadj-Kacem H, Rebuffat S, Mnif-Feki M et al. Autoimmune thyroid diseases: genetic susceptibility of thyroid-specific genes and thyroid autoantigens contributions. Int J Immunogenet 2009;36:85-96. 22. Laurberg P, Cerqueira C, Ovesen L et al. Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res Clin Endocrinol Metab 2010;24:13-27. 23. Bulow Pedersen I, Knudsen N, Jorgensen T et al. Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey. J Clin Endocrinol Metab 2002;87:4462-9. 24. WHO/ICCIDD/UNICEF. Recommended iodine levels in salt and guidelines for monitoring their adequacy and effectiveness 1996. Document WHO/NUT/96.13. Available at http://whqlibdoc. who.int/hq/1996/WHO_NUT_96.13.pdf. Accessed January 14, 2011. 25. Rehman SU, Cope DW, Senseney AD et al. Thyroid disorders in elderly patients. South Med J 2005;98:543-9. 26. Barbesino G. Drugs affecting thyroid function. Thyroid 2010;20:763-70. 27. Dominguez LJ, Bevilacqua M, Dibella G et al. Diagnosing and managing thyroid disease in the nursing home. J Am Med Dir Assoc 2008;9:9-17. 28. Venero CV, Thompson PD. Managing statin myopathy. Endocrinol Metab Clin North Am 2009;38:121-36. 29. Sengul E, Cetinarslan B, Tarkun I et al. Homocysteine concentrations in subclinical hypothyroidism. Endocr Res 2004;30:351-9. 30. Lee JS, Buzkova P, Fink HA et al. Subclinical thyroid dysfunction and incident hip fracture in older adults. Arch Intern Med 2010;170:1876-83. 31. Bona M, Santini F, Rivolta G et al. Cost effectiveness of screening for subclinical hypothyroidism in the elderly. A decisionanalytical model. Pharmacoeconomics 1998;14:209-16. 32. United States Preventive Services Task Force Screening for Thyroid Disease. Available at http://www.uspreventiveservicestaskforce.org/uspstf/uspsthyr.htm. Accessed January 14, 2011. 33. Ladenson PW, Singer PA, Ain KB et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med 2000;160:1573-5. 34. Helfand M, Redfern CC. Clinical guideline, part 2. Screening for thyroid disease: an update. American College of Physicians. Ann Intern Med 1998;129:144-58. 35. American Academy of Family Physicians. Summary of policy recommendations for periodic health examinations June 2010. Available at http://www.aafp.org/exam.xml. Accessed February 4, 2011. 36. Fischbach F. Thyroid function tests. In Fischbach F, Dunning MB, eds. A Manual of Laboratory and Diagnostic Tests, 7th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2004:437-54. 37. Vanderpump MP, Tunbridge WM, French JM et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol 1995;43:55-68. 664 38. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008;29:76-131. 39. Todd CH. Management of thyroid disorders in primary care: challenges and controversies. Postgrad Med J 2009;85:655-9. 40. RLC Labs, Inc. Westhroid Conversion Guide. Available at http://wes-throid.com/conversionChart.asp. Accessed April 14, 2011. 41. Singer PA, Cooper DS, Levy EG et al. Treatment guidelines for patients with hyperthyroidism and hypothyroidism. Standards of Care Committee, American Thyroid Association. JAMA 1995;273:808-12. 42. Grozinsky-Glasberg S, Fraser A, Nahshoni E et al. Thyroxinetriiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 2006;91: 2592-9. 43. Roos A, Linn-Rasker SP, van Domburg RT et al. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial. Arch Intern Med 2005;165:1714-20. 44. Hueston WJ. Treatment of hypothyroidism. Am Fam Physician 2001;64:1717-24. 45. Clarke N, Kabadi UM. Optimizing treatment of hypothyroidism. Treat Endocrinol 2004;3:217-21. 46. Bach-Huynh TG, Nayak B, Loh J et al. Timing of levothyroxine administration affects serum thyrotropin concentration. J Clin Endocrinol Metab 2009;94:3905-12. 47. Bolk N, Visser TJ, Nijman J et al. Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med 2010;170:1996-2003. 48. Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab 2009;23:781-92. 49. Green WL. New questions regarding bioequivalence of levothyroxine preparations: a clinician’s response. AAPS J 2005;30:54-8. 50. The Endocrine Society. Position Statement: Bioequivalence of sodium levothyroxine 2008. Available at http://www.endo-society. org/advocacy/policy/upload/L-T4-Position-Statement-withmember-comments-header.pdf. Accessed January 14, 2011. 51. Mooradian AD. Subclinical hypothyroidism in the elderly: to treat or not to treat? Am J Ther 2010 Jul 10 [Epub Ahead of print]. Doi: 10.1097/MJT.0b013e3181e0ca9c. The Consultant Pharmacist SEPTEMBER 2011 Vol. 26, No. 9