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COVER ARTICLE                                                                                             PRACTICAL THERAP...
TABLE 1                                                  TABLE 2                       Causes of Hypothyroidism           ...
HypothyroidismDiagnosis                                                    In primary hypothyroidism, the thyroid-stimulat...
In most healthy young adults, replacement is  Because levothyroxine can cause increases in the resting heart          init...
Hypothyroidismated no earlier than four weeks after anadjustment in the levothyroxine dosage. The        SUBCLINICAL HYPOT...
(6 to 10 mU per L) are not at risk for subse-              subclinical hypothyroidism. More research is                   ...
Hypothyroidisma physician visit may restore their free T4 lev-    vated, and the patients continue to haveels to normal bu...
Hypothyroidism                       10. Grebe SK, Cooke RR, Ford HC, Fagerstrom JN,                    clinical hypothyro...
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Treatment hypothyroid


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Treatment hypothyroid

  1. 1. COVER ARTICLE PRACTICAL THERAPEUTICSTreatment of HypothyroidismWILLIAM J. HUESTON, M.D., Medical University of South Carolina, Charleston, South CarolinaThyroid disease affects up to 0.5 percent of the population of the United States. Itsprevalence is higher in women and the elderly. The management of hypothy-roidism focuses on ensuring that patients receive appropriate thyroid hormonereplacement therapy and monitoring their response. Hormone replacement shouldbe initiated in a low dosage, especially in the elderly and in patients prone to car-diac problems. The dosage should be increased gradually, and laboratory valuesshould be monitored six to eight weeks after any dosage change. Once a stabledosage is achieved, annual monitoring of the thyroid-stimulating hormone (TSH)level is probably unnecessary, except in older patients. After full replacement ofthyroxine (T4) using levothyroxine, the addition of triiodothyronine (T3) in a lowdosage may be beneficial in some patients who continue to have mood or memoryproblems. The management of patients with subclinical hypothyroidism (a highTSH in the presence of normal free T4 and T3 levels) remains controversial. In thesepatients, physicians should weigh the benefits of replacement (e.g., improved car-diac function) against problems that can accompany the excessive use of levothy-roxine (e.g., osteoporosis). (Am Fam Physician 2001;64:1717-24.) H ypothyroidism is second ation of the thyroid subsequent to only to diabetes mellitus Graves’ disease and surgical removal of as the most common the thyroid gland. endocrine disorder in Long-term thyroid dysfunction after the United States, and its subacute granulomatous thyroiditis prevalence may be as high as 18 cases per (de Quervain’s thyroiditis) or subacute 1,000 persons in the general population.1 lymphocytic thyroiditis (silent or pain- The disorder becomes increasingly com- less thyroiditis) is fairly rare. Full thyroid mon with advancing age, affecting about function is regained in 90 percent of 2 to 3 percent of older women.2 Because patients with these conditions.6 hypothyroidism is so common, family Hypothyroidism can also develop sec- physicians need to know how to diag- ondary to hypothalamic and pituitary nose the disorder and select appropriate disorders. These endocrine conditions thyroid hormone replacement therapy. occur primarily in patients who have undergone intracranial irradiation or Etiology surgical removal of a pituitary adenoma. A number of conditions can lead to hypothyroidism (Table 1).3 Of noniatro- Signs and SymptomsMembers of various fam- genic causes, Hashimoto’s thyroiditis, or The signs and symptoms of hypothy-ily practice departments chronic lymphocytic thyroiditis, is the roidism are nonspecific and may be con-develop articles for“Practical Therapeutics.” most common inflammatory thyroid fused with those of other clinical condi-This article is one in a disorder and the most frequent cause of tions, especially in postpartum womenseries coordinated by the goiter in the United States.4 For an and the elderly. Because of the variety ofDepartment of Family unknown reason, the prevalence of possible manifestations, family physi-Medicine at the Medical Hashimoto’s thyroiditis has been in- cians must maintain a high index of sus-University of South Car-olina, Charleston. Guest creasing dramatically in this country picion for the disorder, especially ineditor of the series is over the past 50 years.5 Other common high-risk groups.William J. Hueston, M.D. causes of hypothyroidism include irradi- Patients with severe hypothyroidismNOVEMBER 15, 2001 / VOLUME 64, NUMBER 10 AMERICAN FAMILY PHYSICIAN 1717
  2. 2. TABLE 1 TABLE 2 Causes of Hypothyroidism Common Signs and Symptoms of Hypothyroidism* Primary hypothyroidism (95% of cases) Idiopathic hypothyroidism* Sign or symptom Affected patients (%) Hashimoto’s thyroiditis Weakness 99 Irradiation of the thyroid subsequent to Graves’ disease Skin changes 97 (dry or coarse skin) Surgical removal of the thyroid Late-stage invasive fibrous thyroiditis Lethargy 91 Iodine deficiency Slow speech 91 Drug therapy (e.g., lithium, interferon) Eyelid edema 90 Infiltrative diseases (e.g., sarcoidosis, amyloidosis, Cold sensation 89 scleroderma, hemochromatosis) Decreased sweating 89 Secondary hypothyroidism (5% of cases) Cold skin 83 Pituitary or hypothalamic neoplasms Thick tongue 82 Congenital hypopituitarism Facial edema 79 Pituitary necrosis (Sheehan’s syndrome) Coarse hair 76 *—Probably old Hashimoto’s thyroiditis (i.e., a Skin pallor 67 “burned out” thyroid from Hashimoto’s thyroiditis). Forgetfulness 66 Adapted with permission from Hueston WJ. Thyroid Constipation 61 disease. In: Rosenfeld JA, Alley N, Acheson LS, Admire JB, eds. Women’s health in primary care. Bal- *—Only signs and symptoms that occur in 60 per- timore: Williams & Wilkins, 1997:617-31. cent or more of patients with hypothyroidism are listed in this table. Adapted with permission from Larsen PR, Davies TF, Hay ID. The thyroid gland. In: Wilson JD, Foster DW, generally present with a constellation of signs Kronenberg HM, Larsen PR, eds. Williams Textbook of endocrinology. 9th ed. Philadelphia: Saunders, and symptoms that may include lethargy, 1998:461. weight gain, hair loss, dry skin, forgetfulness, constipation and depression. Not all of these signs and symptoms occur in every patient, and many may be blunted in patients with tum thyroiditis, which has many of the same mild hypothyroidism. The most common symptoms as postpartum depression. manifestations of hypothyroidism are listed Physical findings in patients with hypothy- in Table 2.7 roidism are also nonspecific. These findings In older patients, hypothyroidism can be can include lowered blood pressure with confused with Alzheimer’s disease and other bradycardia, nonpitting edema, generalized conditions that cause cognitive impairment. hair loss (especially along the outer third of Because depression can be a manifestation the eyebrows), dry skin and a diminished of hypothyroidism, patients with this endo- relaxation phase of reflexes. crine condition may be treated as depressed, A primary challenge is to differentiate the and other signs and symptoms of the disor- generalized symptoms of early hypothy- der may be overlooked. This is particularly roidism from the similar symptoms of true with hypothyroidism that develops or fatigue and depression that occur in many worsens during pregnancy, or with postpar- other conditions.1718 AMERICAN FAMILY PHYSICIAN VOLUME 64, NUMBER 10 / NOVEMBER 15, 2001
  3. 3. HypothyroidismDiagnosis In primary hypothyroidism, the thyroid-stimulating hormone The evaluation of patients with new-onset (TSH) level is elevated, and free thyroid hormone levels arehypothyroidism is quite limited. In patients depressed. In secondary hypothyroidism, the TSH level is lowwith primary hypothyroidism, the thyroid- or undetectable. A follow-up assessment of the free thyrox-stimulating hormone (TSH) level is elevated,indicating that thyroid hormone production ine level can help distinguish between primary and secondaryis insufficient to meet metabolic demands, hypothyroidism.and free thyroid hormone levels are depressed.In contrast, patients with secondary hypothy-roidism have a low or undetectable TSH level. with secondary hypothyroidism, further TSH results have to be interpreted in light investigation with provocative testing of theof the patient’s clinical condition. A low TSH pituitary gland can be performed to deter-level should not be misinterpreted as hyper- mine if the underlying cause is a hypothala-thyroidism in the patient with clinical mani- mic or pituitary disorder. In patients withfestations of hypothyroidism. When symp- pituitary dysfunction, imaging is indicated totoms are nonspecific, a follow-up assessment detect microadenomas, and levels of otherof the free thyroxine (T4) level can help distin- hormones that depend on pituitary stimula-guish between primary and secondary hypo- tion should also be measured. In general, evi-thyroidism. A guide to the laboratory diagno- dence of decreased production of more thansis of hypothyroidism and the interpretation one pituitary hormone is indicative of panhy-of TSH, T4 and triiodothyronine (T3) levels is popituitary problems.provided in Table 3. Once the diagnosis of primary hypothy- Thyroid Hormone Replacementroidism is made, additional imaging or sero- SELECTING THE APPROPRIATE AGENTlogic testing is unnecessary if the thyroid Thyroid medications were once preparedgland is normal on examination. In patients from desiccated samples of ground thyroidTABLE 3Laboratory Values in HypothyroidismTSH level Free T4 level Free T3 level Likely diagnosisHigh Low Low Primary hypothyroidismHigh (> 10 µU per mL Normal Normal Subclinical hypothyroidism with high risk for future [10 mU per L]) development of overt hypothyroidismHigh (6 to 10 µU per mL Normal Normal Subclinical hypothyroidism with low risk for future [6 to 10 mU per L]) development of overt hypothyroidismHigh High Low Congenital absence of T4-T3–converting enzyme; amiodarone (Cordarone) effect on T4-T3 conversionHigh High High Peripheral thyroid hormone resistanceLow Low Low Pituitary thyroid deficiency or recent withdrawal of thyroxine after excessive replacement therapyTSH = thyroid-stimulating hormone; T4 = thyroxine; T3 = triiodothyronine.NOVEMBER 15, 2001 / VOLUME 64, NUMBER 10 AMERICAN FAMILY PHYSICIAN 1719
  4. 4. In most healthy young adults, replacement is Because levothyroxine can cause increases in the resting heart initiated using levothyroxine in a dosage of rate and blood pressure, replacement should begin at a low 0.075 mg per day, with the dosage increased slowly as indicated by continued elevation of dosage in older patients and patients at risk for cardiovascular the TSH level. compromise. Levothyroxine should be initiated in a low dosage in older patients and those at risk for the cardiovascular compromise that could glands from cows, and standardization was occur with a rapid increase in resting heart based on the iodine content of the extract rate and blood pressure.9 In these patients, rather than its T3 or T4 content. The actual the usual starting dosage is 0.025 mg per day. thyroid hormone content of the products This dosage can be increased in increments of varied considerably from manufacturer to 0.025 to 0.050 mg every four to six weeks manufacturer, and even within products from until the TSH level returns to normal. the same manufacturer, depending on the Thyroid hormone is usually given once thyroid status of the cows. Fortunately, this daily, but some evidence suggests that weekly method of preparing thyroid hormone has dosing may also be effective. In a small study10 been abandoned, and replacement is now of 12 patients with hypothyroidism, a bolus accomplished primarily with synthetic thy- dose of thyroid hormone equal to seven times roid hormones. the usual daily dose was well tolerated. Before A recent analysis8 of four levothyroxine weekly replacement can be recommended, preparations, including two brand-name however, more investigation is required, products (Synthroid and Levoxyl) and two including definitions of the populations in generic preparations, demonstrated relative which this approach is indicated. bioequivalence. Patients switched from any In a study11 of 33 middle-aged patients one of the four preparations to another (mostly women) with stable hypothyroidism showed insignificant variations in their thy- who were already receiving levothyroxine, roid function tests. Among the four products, small improvements in mood, memory and the only difference noted was that Synthroid cold tolerance occurred after triiodothyro- produced a more rapid and higher rise in the nine was added, in a dosage of 0.0125 mg per T3 level after administration. However, the day, with a concomitant 0.05-mg decrease in difference was not statistically significant and the usual levothyroxine dosage. Although this is of questionable clinical importance. study was small, it suggests that some patients who are chemically euthyroid but have linger- INITIATING TREATMENT ing neuropsychiatric problems might benefit Most otherwise healthy adult patients with from triiodothyronine. Further investigation hypothyroidism require thyroid hormone is required to determine the role of tri- replacement in a dosage of 1.7 µg per kg per iodothyronine in these patients, as well as the day, with requirements falling to 1 µg per kg long-term consequences of its use. per day in the elderly. Thus, levothyroxine in a dosage of 0.10 to 0.15 mg per day is needed MONITORING THYROID FUNCTION to achieve euthyroid status. For full replace- In patients with an intact hypothalamic- ment, children may require up to 4 µg per kg pituitary axis, the adequacy of thyroid hor- per day.9 mone replacement can be followed with ser- In young patients without risk factors for ial TSH assessments. However, changes in the cardiovascular disease, thyroid hormone TSH level lag behind serum thyroid hormone replacement can start close to the target goal. levels. Thus, the TSH level should be evalu-1720 AMERICAN FAMILY PHYSICIAN VOLUME 64, NUMBER 10 / NOVEMBER 15, 2001
  5. 5. Hypothyroidismated no earlier than four weeks after anadjustment in the levothyroxine dosage. The SUBCLINICAL HYPOTHYROIDISMfull effects of thyroid hormone replacement The TSH level can be mildly elevated whenon the TSH level may not become apparent the free T4 and T3 levels are normal, a situationuntil after eight weeks of therapy.12 that occurs most often in women and becomes In patients with pituitary insufficiency, increasingly common with advancing age.measurements of free T4 and T3 levels can be This condition has been termed “subclinicalperformed to determine whether patients hypothyroidism,” based on the suppositionremain euthyroid. In these patients, the goal is that it reflects early failure of the thyroid hor-to maintain free thyroid hormone levels in mone and eventual development of hypothy-the middle to upper ranges of normal to roidism.17 However, it appears that patientsensure adequate replacement. with a TSH level between 6 and 10 µU per mL TSH or free T4 levels are monitored annu-ally in most patients with hypothyroidism, al-though no data support this practice. Gener- Treatment of Hypothyroidismally, once a stable maintenance dosage oflevothyroxine is achieved, that dosage will re- Is there a documented need formain adequate until patients are 60 to 70 years thyroid hormone replacement?of age. With age, thyroid binding maydecrease, and the serum albumin level maydecline. In this setting, the levothyroxine Is the patient > 50 years of age and/or at risk for cardiac disease?dosage may need to be reduced by up to20 percent.13,14 Although less frequent thanannual monitoring could be justified in Yes Noyounger adult patients whose weight is stable,annual monitoring in older patients is neces- Start levothyroxine, Start levothyroxine,sary to avoid overreplacement.15 0.025 to 0.05 mg per day. 0.075 mg per day. A guideline for initiating and monitoringthyroid hormone replacement therapy is pro-vided in Figure 1. Monitor TSH level (if primary hypothyroidism)INTRAVENOUS REPLACEMENT or free T4 level (if secondary hypothyroidism) every 6 to 8 weeks; adjust levothyroxine Because thyroid hormone has a large vol- dosage until laboratory tests are normal.ume of distribution and long half-life, par-enteral replacement is unnecessary inpatients who are unable to take medication Does the patient still have lethargy or memory problems?orally for a few days to a week. However,some patients may be unable to take oralmedications for much longer periods. Intra-venous administration is advised in these Yes Nopatients and in those who need to begin thy- Consider adding triiodothyronine, Continue to monitor TSHroid hormone replacement but cannot take 0.0125 mg per day (although or T4 levels annually.oral medications. Only about 70 to 80 per- long-term effects are not known).cent of an oral dose of replacement medica-tion is absorbed. Therefore, parenteralreplacement should be initiated at 70 to 80 FIGURE 1. Initiation and monitoring of treatment for hypothyroidism.percent of the usual oral dose.16 (TSH = thyroid-stimulating hormone; T4 = thyroxine)NOVEMBER 15, 2001 / VOLUME 64, NUMBER 10 AMERICAN FAMILY PHYSICIAN 1721
  6. 6. (6 to 10 mU per L) are not at risk for subse- subclinical hypothyroidism. More research is quent hypothyroidism.1 In contrast, patients needed to sort out the most appropriate with a higher TSH level (above 10 µU per mL) management. progress to overt hypothyroidism at a rate of 1 to 20 percent per year.1 Conditions Affecting Thyroid Hormone Thyroid hormone replacement may have Replacement Requirements some benefits in patients with subclinical Because thyroid hormone is highly protein hypothyroidism, but there is also a potential bound, medical conditions that alter the for adverse effects, particularly in older amount of binding hormones and drugs that patients. Some studies have shown that sup- compete for binding may change the amount plementation of thyroid hormone accelerates of available free thyroid hormone. The thy- bone mineral loss in older women with sub- roid replacement dosage must be changed in clinical hypothyroidism, and that estrogen response to alterations in binding status. replacement therapy does not counteract this With conditions that cause an increase in effect.17 Bone-wasting effects have not been serum binding proteins, such as high estro- observed in patients who are clinically hypo- gen states (e.g., pregnancy), oral contracep- thyroid and receive adequate thyroid hor- tive use or postmenopausal estrogen replace- mone replacement therapy.18 ment, the dosage of levothyroxine must be Thyroid hormone replacement has also increased. In contrast, androgens decrease been reported to decrease serum homocys- levels of thyroid binding proteins, necessitat- teine levels.19 Along with changes in lipids, ing a reduction in the dosage. Older patients hyperhomocysteinemia may be one of the also have lower serum protein levels and may mechanisms through which hypothyroidism require reductions in their maintenance is associated with an increased risk for cardio- dosage over time. Nephrosis, protein-losing vascular disease.20 enteropathies and cirrhosis are other condi- At this time, the approach to patients with tions that require a reduced thyroid hor- subclinical hypothyroidism must be individ- mone dosage. ualized. In patients at higher risk for osteo- A number of medications reduce the porosis or fractures, the deleterious effects of absorption of thyroid hormone from the excessive thyroid hormone can be avoided by intestines, necessitating an increase in the withholding replacement until the free T4 replacement dosage (Table 4).21 Other drugs and T3 levels drop below normal. In patients accelerate the metabolism of thyroid hor- with hyperhomocysteinemia, existing car- mone, and an increase in the replacement diac disease or risk factors for heart disease, dosage is then required. When these medica- early thyroid hormone replacement may tions are started or adjusted, the TSH value offer more advantages. Right now, consensus should be monitored to determine whether is lacking on how to manage patients with additional thyroid hormone replacement is indicated. Persistently Elevated TSH DespiteThe Author Thyroid Hormone ReplacementWILLIAM J. HUESTON, M.D., is professor and chair of the Department of Family Medi- Poor compliance is the most common rea-cine at the Medical University of South Carolina, Charleston. He received his medical son for continued elevation of the TSH leveldegree from Case Western Reserve University School of Medicine, Cleveland, and com-pleted a family practice residency at Riverside Methodist Hospital, Columbus, Ohio. in patients receiving presumably adequate thyroid hormone replacement. Patients whoAddress correspondence to William J. Hueston, M.D., Department of Family Medicine,Medical University of South Carolina, P.O. Box 250192, Charleston, SC 29425 (e-mail: do not regularly take their replacement Reprints are not available from the author. ication and then try to “catch up” just before1722 AMERICAN FAMILY PHYSICIAN VOLUME 64, NUMBER 10 / NOVEMBER 15, 2001
  7. 7. Hypothyroidisma physician visit may restore their free T4 lev- vated, and the patients continue to haveels to normal but continue to have an elevated symptoms of hypothyroidism. These patientsTSH level. should be referred to an endocrinologist for Very rarely, patients have tissue-level unre- further evaluation and management.sponsiveness to thyroid hormone. This con-dition reflects a mutation in the gene that Screening for Hypothyroidismcontrols a receptor for T3, rendering it unable The U.S. Preventive Services Task Force23to bind with the hormone. The genetic muta- does not recommend routine screening fortion has been identified in only 300 families.22 hypothyroidism in asymptomatic persons.In these patients, adequate amounts of thy- Recently, some expert panels24 noted thatroid hormone are produced but are ineffec- screening may be beneficial in high-risk pop-tive. Consequently, the TSH level remains ele- ulations such as elderly women. However, widespread screening is not likely to be cost- effective. Because of the nonspecific symp-TABLE 4 toms of hypothyroidism, many patientsDrugs Potentially Altering Thyroid would be tested because of their symptoms.Hormone Replacement Requirements This practice should not be confused with asymptomatic screening.Increase replacement requirements The author indicates that he does not have any con-Drugs that reduce thyroid hormone production flicts of interest. Sources of funding: none reported. Lithium Iodine-containing medications REFERENCES Amiodarone (Cordarone) 1. Helfand M, Crapo LM. Screening for thyroid dis-Drugs that reduce thyroid hormone absorption ease. Ann Intern Med 1990;112:840-9. Sucralfate (Carafate) 2. Sawin CT, Chopra D, Azizi F, Mannix JE, Bacharach Ferrous sulfate (Slow Fe) P. The aging thyroid. Increased prevalence of ele- Cholestyramine (Questran) vated serum thyrotropin levels in the elderly. JAMA 1979;242:247-50. Colestipol (Colestid) 3. Hueston WJ. Thyroid disease. In: Rosenfeld JA, Aluminum-containing antacids Alley N, Acheson LS, Admire JB, eds. Women’s Calcium products health in primary care. Baltimore: Williams & Wilkins, 1997:617-31.Drugs that increase metabolism of thyroxine 4. Farwell AP, Braverman LE. Inflammatory thyroid Rifampin (Rifadin) disorders. Otolaryngol Clin North Am 1997;29: Phenobarbital 541-56. Carbamazepine (Tegretol) 5. Hay ID. Thyroiditis: a clinical update. Mayo Clin Warfarin (Coumadin) Proc 1985;60:836-43. 6. Schubert MF, Kountz DS. Thyroiditis. A disease Oral hypoglycemic agents with many faces. Postgrad Med 1995;98(2):101-Increase thyroxine availability and may decrease 3,107-8,112. replacement requirements 7. Larsen PR, Davies TF, Hay ID. The thyroid gland. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR,Drugs that displace thyroid hormone from protein eds. Williams Textbook of endocrinology. 9th ed. binding Philadelphia: Saunders, 1998:461. Furosemide (Lasix) 8. Dong BJ, Hauck WW, Gambertoglio JG, Gee L, Mefenamic acid (Ponstel) White JR, Bubp JL, et al. Bioequivalence of generic and brand-name levothyroxine products in the Salicylates treatment of hypothyroidism. JAMA 1997;277: 1205-13.Adapted with permission from Surks MI, Sievert R. 9. Singer PA, Cooper DS, Levy EG, Ladenson PW,Drugs and thyroid function. N Engl J Med 1995; Braverman LE, Daniels G, et al. Treatment guidelines for patients with hyperthyroidism and hypothy-333:1688-94. roidism. Standards of Care Committee, American Thyroid Association. JAMA 1995;273:808-12.NOVEMBER 15, 2001 / VOLUME 64, NUMBER 10 AMERICAN FAMILY PHYSICIAN 1723
  8. 8. Hypothyroidism 10. Grebe SK, Cooke RR, Ford HC, Fagerstrom JN, clinical hypothyroidism. Gynecol Endocrinol 1999; Cordwell DP, Lever NA, et al. Treatment of hypo- 13:196-201. thyroidism with once weekly thyroxine. J Clin 18. Hanna FW, Pettit RJ, Ammari F, Evans WD, Sande- Endocrinol Metab 1997;82:870-5. man D, Lazarus JH. Effect of replacement doses of 11. Bunevicius R, Kazanavicius G, Zalinkevicius R, thyroxine on bone mineral density. Clin Endocrinol Prange AJ Jr. Effects of thyroxine as compared with [Oxf] 1998;48:229-34. thyroxine plus triiodothyronine in patients with 19. Hussein WI, Green R, Jacobsen DW, Fairman C. hypothyroidism. N Engl J Med 1999;340:424-9. Normalization of hyperhomocysteinemia with 12. Carr D, McLeod DT, Parry G, Thornes HM. Fine L-Thyroxine in hypothyroidism. Ann Intern Med adjustment of thyroxine replacement dosage: com- 1999;131:348-51. parison of the thyrotrophin releasing hormone test 20. Green R, Chong YY, Jacobsen DW, Robinson K, using a sensitive thyrotrophin assay with measure- Gupta M. Serum homocysteine is high in hypothy- ment of free thyroid hormones and clinical assess- roidism: a possible link with coronary artery dis- ment. Clin Endocrinol [Oxf] 1988;28:325-33. ease. Presented at the International Conference on 13. Rosenbaum RL, Barzel US. Levothyroxine replace- Homocysteine Metabolism, from Basic Science to ment dose for primary hypothyroidism decreases Clinical Medicine. Ireland, July 2-5, 1995. Ir J Med with age. Ann Intern Med 1982;96:53-5. Sci 1995;164(suppl 15):27-8. 14. Sawin CT, Geller A, Hershman JM, Castelli W, 21. Surks MI, Sievert R. Drugs and thyroid function. Bacharach P. The aging thyroid. The use of thyroid N Engl J Med 1995;333:1688-94. hormone in older persons. JAMA 1989;261:2653-5. 22. Refetoff S, Weiss RE, Usala SJ. The syndromes of 15. Hays MT, Nielsen KR. Human thyroxine absorption: resistance to thyroid hormone. Endocr Rev 1993; age effects and methodological analyses. Thyroid 14:348-99. 1994;4:55-64. 23. Guide to clinical and preventive services: report of 16. Wallace K, Hoffman MT. Thyroid dysfunction: how the U.S. Preventive Services Task Force. 2d ed. Bal- to manage overt and subclinical disease in older timore: Williams & Wilkins, 1996:209-18. patients. Geriatrics 1998;53:32-8,41. 24. Helfand M, Redfern CC. Clinical guideline, part 2. 17. Pines A, Dotan I, Tabori U, Villa Y, Mijatovic V, Leno Screening for thyroid disease: an update. American Y, et al. L-Thyroxine prevents the bone-conserving College of Physicians. Ann Intern Med 1998;129: effect of HRT in postmenopausal women with sub- 144-58.1724 AMERICAN FAMILY PHYSICIAN VOLUME 64, NUMBER 10 / NOVEMBER 15, 2001