In the Clinic Hyperthyroidism In theClinic...In the Clinic Hyperthyroidism Screening page ITC1-2...

In the Clinic

HyperthyroidismScreening page ITC1-2

Diagnosis page ITC1-3

Treatment page ITC1-7

Practice Improvement page ITC1-13

Tool Kit page ITC1-14

Patient Information page ITC1-15

CME Questions page ITC1-16

Physician WriterMichael T. McDermott, MD

Section EditorsDeborah Cotton, MD, MPHDarren Taichman, MD, PhDSankey Williams, MD

The content of In the Clinic is drawn from the clinical information and educationresources of the American College of Physicians (ACP), including PIER (Physicians’Information and Education Resource) and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinicfrom these primary sources in collaboration with the ACP’s Medical Education andPublishing divisions and with the assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of thecontent. Readers who are interested in these primary resources for more detail canconsult http://pier.acponline.org, http://www.acponline.org/products_services/mksap/15/?pr31, and other resources referenced in each issue of In the Clinic.

CME Objective: To review current evidence for the prevention, diagnosis, andtreatment of hyperthyroidism.

The information contained herein should never be used as a substitute for clinicaljudgment.

© 2012 American College of Physicians Inthe

Clinic

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Who has an elevated risk forhyperthyroidism?People at increased risk for hyper-thyroidism include those with diffuse or nodular goiters, type 1diabetes mellitus, other endocrineand nonendocrine autoimmune dis-eases, and family histories of hyper-thyroidism or hypothyroidism.Medications that increase the riskfor hyperthyroidism include amio-darone (4, 5), alpha-interferon (6),interleukin-2 (7), lithium (8), andiodide (9). The iodinated contrastagents administered for imagingstudies also increase risk for hyper-thyroidism in individuals who havepreexisting autoimmune or nodularthyroid disease.

Should clinicians screen forhyperthyroidism?Screening for hyperthyroidism inthe general population is not cost-effective because of the low preva-lence of the disorder. It is prudent,however, to screen people who areat high risk when they have thecomorbid conditions, family history, or medication use described in theprevious section. Screening shouldalso be considered in patients who

have other medical conditions thatmay be caused or aggravated byhyperthyroidism, such as osteo-porosis, supraventricular tachycar-dia, or atrial fibrillation. Screeningmay also be more cost-effective in women older than 50 years ofage (10), because 1 out of every 71 women in this age group hasunsuspected but symptomatic hyperthyroidism or hypothy-roidism that responds well totreatment. As a result, screeningwomen over age 50 is recom-mended, especially because theTSH test that screens for hyper-thyroidism also screens for hy-pothyroidism, a disorder that ismore common in this population.

If clinicians screen forhyperthyroidism, which test should they use?Measuring serum TSH levels is thebest way to screen for hyperthy-roidism. Serum TSH becomes lowin both overt and subclinical hyper-thyroidism because of negativefeedback by elevated thyroid hor-mone levels on the pituitary gland,and TSH assays are standardized,accurate, and widely available.

© 2012 American College of Physicians ITC1-2 In the Clinic Annals of Internal Medicine 3 July 2012

1. Singer PA, Cooper DS,Levy EG, et al. Treat-ment guidelines for patients with hy-perthyroidism andhypothyroidism.Standards of CareCommittee, Ameri-can Thyroid Associa-tion. JAMA.1995;273:808-12.[PMID: 7532241]

2. Hollowell JG,Staehling NW, Flan-ders WD, et al. SerumTSH, T(4), and thyroidantibodies in theUnited States popula-tion (1988 to 1994):National Health andNutrition Examina-tion Survey (NHANESIII). J Clin EndocrinolMetab. 2002;87:489-99. [PMID: 11836274]

3. Bahn RS, Burch HB,Cooper DS, et al. Hy-perthyroidism andother causes of thyro-toxicosis: manage-ment guidelines ofthe American ThyroidAssociation andAmerican Associationof Clinical Endocri-nologists. Thyroid2011; 21:593-646).[PMID: 21700562]

4. Newman CM, Price A,Davies DW, Gray TA,Weetman AP. Amio-darone and the thy-roid: a practical guideto the managementof thyroid dysfunc-tion induced byamiodarone therapy.Heart. 1998;79:121-7.[PMID: 9538302]

5. Piga M, Serra A, Boi F,Tanda ML, Martino E,Mariotti S. Amiodarone-induced thyrotoxico-sis. A review. MinervaEndocrinol.2008;33:213-28.[PMID: 18846027]

Hyperthyroidism is a clinical state characterized by excessive serumconcentrations of thyroxine (T4 ), triiodothyronine (T3 ), or bothwith suppression of serum thyroid-stimulating hormone (TSH)

levels. Some observers prefer the term thyrotoxicosis for this condition and restrict the term hyperthyroidism to the types of thyrotoxicosis that are caused when the thyroid gland synthesizes and secretes too much thyroid hormone. To avoid confusion, however, we will consider hyperthyroidism and thyrotoxicosis to be the same and will use only theterm hyperthyroidism.

Hyperthyroidism is considered to be “overt” when a low serum TSH levelis associated with elevated serum levels of free or total T4 and/or free or total T3. Hyperthyroidism is considered to be “subclinical” when a lowserum TSH level is associated with serum T4 and T3 levels that are withinthe population reference range. Therefore, the terms overt and subclinical aredefined biochemically without reference to clinical features. Althoughsymptoms and signs are usually prominent in overt hyperthyroidism, theymay or may not be present in subclinical hyperthyroidism. The prevalenceof hyperthyroidism in the United States is estimated to be about0.4%–1.2%, with approximately 40% of cases being overt and 60% beingsubclinical (1–3).

Screening


© 2012 American College of PhysiciansITC1-3In the ClinicAnnals of Internal Medicine3 July 2012

6. Dumoulin FL, LeifeldL, Sauerbruch T,Spengler U. Autoim-munity induced byinterferon-alpha ther-apy for chronic viralhepatitis. BiomedPharmacother.1999;53:242-54.[PMID: 10424246]

7. Vialettes B, GuillerandMA, Viens P, et al. Inci-dence rate and riskfactors for thyroiddysfunction duringrecombinant interleukin-2 therapyin advanced malig-nancies. Acta En-docrinol (Copenh).1993;129:31-8. [PMID: 8351956]

8. Miller KK, Daniels GH.Association betweenlithium use and thy-rotoxicosis caused bysilent thyroiditis. ClinEndocrinol (Oxf ).2001;55:501-8.[PMID: 11678833]

9. Stanbury JB, ErmansAE, Bourdoux P, et al.Iodine-induced hyperthyroidism: oc-currence and epi-demiology. Thyroid.1998;8:83-100.[PMID: 9492158]

10. U.S. Preventive Serv-ices Task Force.Screening for thyroiddisease: recommen-dation statement.Ann Intern Med.2004;140:125-7.[PMID: 14734336]

11. Trivalle C, Doucet J, Chassagne P, et al.Differences in thesigns and symptomsof hyperthyroidismin older andyounger patients. J Am Geriatr Soc.1996;44:50-3.[PMID: 8537590]

12. Martin FI, Deam DR.Hyperthyroidism inelderly hospitalisedpatients. Clinical fea-tures and treatmentoutcomes. Med JAust. 1996;164:200-3.[PMID: 8604186]

What physical examinationfindings indicate possiblehyperthyroidism?The physical signs often identifiedin hyperthyroid patients includetachycardia; goiter; skin changes;tremor; thyroid bruit; and eye signs,such as stare and lid lag. Some fea-tures of the physical examinationmay also be useful in determiningthe cause of hyperthyroidism. Thediagnosis of Graves disease is sug-gested by a diffuse goiter; a thyroidbruit; eye signs, such as proptosis,chemosis, periorbital edema, ex-traocular muscle dysfunction, oroptic neuropathy (inflammatory orbitopathy); pretibial myxedemaor other, less common, dermato -pathies; soft tissue enlargement and clubbing of the fingers (thyroidacropachy); vitiligo; or prematurehair graying. The diagnosis of atoxic multinodular goiter or a toxicadenoma is supported by the find-ing of multiple thyroid nodules or asingle thyroid nodule on thyroidpalpation. Fever and marked thy-roid tenderness are findings thatpoint to subacute thyroiditis. Table 1 lists the frequencies ofmany physical examination findingsin hyperthyroid patients.

What laboratory tests shouldclinicians use to diagnosehyperthyroidism?Serum TSH measurement is the best test to diagnose hyper-thyroidism. Levels will be low inboth overt and subclinical hyper-thyroidism. If the TSH level islow, the clinician should order a

What symptoms should promptclinicians to considerhyperthyroidism?Symptoms that suggest hyper-thyroidism include nervousness,increased sweating, heat intoler-ance, palpitations, fatigue, weightloss, tachycardia, dyspnea, weak-ness, leg edema, eye symptoms,emotional lability, and frequentdefecation without an increase instool weight (hyperdefecation).Elderly hyperthyroid patients often have milder, more subtle,and less typical symptoms thatare often dominated by fatigue,depression, weight loss, and atrial fibrillation (11, 12). The term apathetic hyperthy-roidism describes this clinicalpresentation.

Some elements of the history may also suggest a specific causeof the hyperthyroidism. Eye pain or swelling, double vision, or a skin disorder on the shinssuggests Graves disease. Recentpregnancy raises the possibility of postpartum thyroiditis. Ante-rior neck pain, malaise, fever, andsore throat are characteristic ofsubacute thyroiditis. Amiodarone,lithium, alpha-interferon, interleukin-2, or potassium iodide use before or recent exposure toiodinated radiocontrast agents increases the likelihood of drug-induced or iodine-induced hyper-thyroidism. Table 1 lists the frequency of several hyperthyroidsymptoms.

Screening... Screening for hyperthyroidism in the general population is not cost-effective, but experts recommend screening with a test for serum TSH in personswith diffuse or nodular goiters, type 1 diabetes mellitus, other endocrine andnonendocrine autoimmune diseases, osteoporosis, supraventricular tachycardia, oratrial fibrillation; in those with family histories of hyperthyroidism or hypothy-roidism; in those taking amiodarone, alpha-interferon, interleukin-2, lithium, oriodide; and in women older than 50 years of age.

CLINICAL BOTTOM LINE

Diagnosis



Table 1. Frequency of Elements from the History and Physical Examination in Hyperthyroidism*Variable Category Element Frequency, %

Clinical hyperthyroidism History Nervousness 99Increased sweating 91Heat intolerance 89Palpitations 89Fatigue 88Weight loss 85Tachycardia 82Dyspnea 75Weakness 70Leg swelling 65Eye signs 54Hyperdefecation 33Weight gain 5–10Menstrual irregularity 22Emotional lability 30–60

Physical examination Tachycardia 100Goiter 100Skin changes 97Tremor 97Bruit 77Eye signs 30–45Atrial fibrillation 10Splenomegaly 10Gynecomastia 10

Subclinical thyroiditis History Neck pain 91Radiation to ears 64Sore throat 36Malaise 84Recent upper respiratory illness 18Anorexia 18Myalgia 12Nervousness 46Perspiration 46

Physical examination Thyroid firm in consistency 100Bilateral thyroid enlargement 45Appearing acutely ill 50Fever 57Eye signs (lid lag, stare) 11

Notes

Findings specific to Physical examination Ophthalmopathy Refers to soft tissue inflammation, proptosis, Graves disease extraocular muscle dysfunction, and rarely optic

neuropathy; stare and lid lag are nonspecific findings in thyrotoxicosis

Diffuse thyroid enlargement Rare nodular forms of Graves disease (Marine–Lenhart variety) exist

Thyroid bruit The author is aware of 1 case in which a large autonomous nodule was associated with a bruit, presumably resulting from compression of the ipsilateral carotid artery

Graves dermopathy Localized myxedema may occur anywhere in the body but is most frequently seen in the pretibial region and the hands

Thyroid acropachy Soft tissue enlargement of the fingers with clubbingVitiligo and premature Suggestive of organ-specific autoimmunityhair graying

* Adapted and updated from Williams RH. Thiouracil treatment of thyrotoxicosis. J Clin Endocrinol 1946;6:1-22.


13. Dydek GJ, Blue PW.Human breast milk excretion of iodine-131 followingdiagnostic and ther-apeutic administra-tion to a lactatingpatient with Graves’disease. J Nucl Med.1988;29:407-10.[PMID: 3346746]

14. Morita S, Umezaki N,Ishibashi M, Kawa-mura S, Inada C,Hayabuchi N. Deter-mining the breast-feeding interruptionschedule after ad-ministration of 123I-iodide. AnnNucl Med. 1998;12:303-6. [PMID: 9839494]

15. Gorman CA. Ra-dioiodine and preg-nancy. Thyroid.1999;9:721-6.[PMID: 10447020]

16. Abalovich M, AminoN, Barbour LA, et al.Management of thy-roid dysfunctionduring pregnancyand postpartum: anEndocrine Societyclinical practiceguideline. J Clin En-docrinol Metab.2007;92:s1-7.


free T4 or a free T4 index (FT4 I).If the free T4 or FT4 I is not ele-vated, the clinician should order a total T3 or free T3 because somepatients have normal T4 levelswith elevated T3 levels (i.e., T3 toxicosis).

Once the diagnosis of hyperthy-roidism is confirmed, further test-ing may be necessary to determinethe cause. When the symptomsand physical signs strongly pointto Graves disease, it is reasonableto forgo further diagnostic testing.If the cause is not clear, the clini-cian should order additional testsbecause treatment differs consid-erably for different causes. The radioiodine uptake (RAIU) is themost useful additional diagnostictest and should be ordered whenever the presentation is notdiagnostic of Graves disease. Hyperthyroidism associated withhigh RAIU usually results from 1 of 3 disorders: Graves disease,toxic multinodular goiter, or a toxic adenoma. The Box (Differ-ential Diagnosis of the Cause ofHyperthyroidism Through Use of Radioiodine Uptake) shows the various causes of hyperthy-roidism and how they can be

categorized according to theRAIU.

A thyroid scan, which can be done at the same time as theRAIU, helps to distinguish among these 3 high RAIU disor-ders and should be done, espe-cially in the presence of thyroidnodularity (3). Graves diseaseshows diffuse isotope uptake, toxicmultinodular goiter shows patchyuptake, and a toxic adenomashows uptake only in a singlenodule. Other tests may be considered when radioisotopestudies are contraindicated—forexample, because of pregnancy or breast-feeding (13–16) or pa-tient preference—and includetests of serum for TSH-receptorantibodies (TRAb), thyroid-stimulating immunoglobulins(TSI), thyroid-peroxidase anti-bodies (TPO), thyroglobulin, andhuman chorionic gonadotropin;erythrocyte sedimentation rate;imaging the thyroid with colorDoppler ultrasonography; and awhole-body radioiodine scan.Table 2 lists tests that are usefulin the diagnosis and differentialdiagnosis of hyperthyroidism.

What alternative explanationsshould clinicians consider inpatients with possiblehyperthyroidism?Conditions with clinical featuresthat can resemble those of hyper-thyroidism include infection, sepsis,anxiety, depression, the chronic fa-tigue syndrome, atrial fibrillation ofother causes, and pheochromocy-toma. Thyroid hormone testing willusually distinguish most of thesedisorders from hyperthyroidism.However, other conditions can be a greater challenge because serumTSH levels are often low in theseconditions, which include preg-nancy; hyperemesis gravidarum;the euthyroid sick syndrome (thenonthyroidal illness syndrome);central hypothyroidism; and the use of some medications, most

Differential Diagnosis of the Causeof Hyperthyroidism Through Use ofRadioiodine Uptake

High or NormalGraves diseaseToxic multinodular goiterToxic adenomaHuman chorionic gonadotropin–induced

hyperthyroidismThyroid stimulating hormone–producing

pituitary tumor

LowSilent thyroiditisPostpartum thyroiditisSubacute (granulomatous) thyroiditisIodine-induced hyperthyroidismAmiodarone-induced hyperthyroidismIatrogenic hyperthyroidismMetastatic follicular thyroid cancerStruma ovarii


17. Spencer C, Eigen A,Shen D, Duda M,Qualls S, Weiss S, etal. Specificity of sen-sitive assays of thy-rotropin (TSH) usedto screen for thyroiddisease in hospital-ized patients. ClinChem. 1987;33:1391-6. [PMID: 3301067]

18. Manji N, Carr-SmithJD, Boelaert K, et al.Influences of age,gender, smoking,and family historyon autoimmune thy-roid disease pheno-type. J Clin Endocrinol Metab.2006;91:4873-80.[PMID: 16968788]


notably glucocorticoids, dopamine,and heparin (17).

When should clinicians consult an endocrinologist for diagnosing possiblehyperthyroidism?The clinician should consider con-sulting an endocrinologist when thepresence of hyperthyroidism is un-certain, such as when the serumTSH level is low but the T4 and T3are within the population referencerange, or when the TSH level is

normal but the T4 or T3 is abovethe reference range. Consultationmay also be helpful when thecause is unclear; this is most often true when RAIU is low orundetectable, whereas the diagno-sis is usually relatively straight-forward when RAIU is elevated.Consultation should also bestrongly considered when theprovider is uncertain or suspiciousabout the risk for or the presenceof thyroid storm or Graves orbitopathy.

Diagnosis... The clinician should make the diagnosis of hyperthyroidism fromthe history, physical examination, and characteristic laboratory findings of a lowserum TSH level associated with elevated serum levels for free T4 , FT4 I, total T3 ,or free T3 . The clinician should identify the cause of hyperthyroidism from clini-cal features along with the RAIU and thyroid scan. In selected situations, theadditional tests described in Table 2 (TRAb, TSI, TPO antibodies, thyroglobulin,erythrocyte sedimentation rate, human chorionic gonadotropin, color Dopplerultrasonography, and whole-body scanning) may facilitate determining thecause.


Table 2. Laboratory and Other Studies for HyperthyroidismTest Indication

TSH Suspected hyperthyroidism

FT4

Suppressed TSH

FT3

Suppressed TSH, normal FT4

Thyroglobulin Suspected thyroiditis

ESR Suspected subacute thyroiditis

TSH-receptor antibodies Euthyroid Graves ophthalmopathy; assessing remission during antithyroid drug therapy in Graves disease; assessing neonatal risk in pregnant patients with Graves disease

Thyroid peroxidase antibodies Confirming Hashimoto thyroiditis and autoimmune thyroid disease in general (including Graves disease); assessing risk for drug-induced thyroid dysfunction and postpartum thyroiditis

RAIU Confirmed biochemical thyrotoxicosis, if cause unclear

Thyroid scan Confirmed biochemical thyrotoxicosis, if cause unclear

Whole body scan Suspected struma ovarii

Color Doppler ultrasonography Differentiating type I and type II amiodarone-induced thyrotoxicosis

HCG Choriocarcinoma

ESR = erythrocyte sedimentation rate; FT3 = free triiodothyronine; FT4 = free thyroxine ; HCG = human chorionic gonadotropin; RAIU = radioactive iodine uptake; TSH = thyroid-stimulating hormone.


19. Eckstein A, Quad-beck B, Mueller G, etal. Impact of smok-ing on the responseto treatment of thy-roid associated oph-thalmopathy. Br JOphthalmol.2003;87:773-6.[PMID: 12770979]

20. Cooper DS. Antithy-roid drugs. N Engl JMed. 2005;352:905-17. [PMID: 15745981]


TreatmentHow should clinicians choose andprescribe drug therapy?Table 3 describes the medicationsavailable for the treatment of hy-perthyroidism. Beta-adrenergicblockade is appropriate for sympto-matic patients with hyperthy-roidism of any cause (3). Clinicianshave successfully used many differ-ent beta-adrenergic blockers totreat this condition.

Methimazole and propylthiouracil(PTU) are the 2 antithyroid med-ications that are available in theUnites States (20). These agents

What nondrug therapies shouldclinicians recommend?Until thyroid disease is adequatelycontrolled, patients with hyperthy-roidism should avoid heavy physicalexertion; reduce or eliminate caffeineintake (to avoid aggravating thesymptoms); avoid over-the-counterdecongestants and cold remedies; dis-continue smoking (smoking promotesophthalmopathy and disease recur-rence) (18, 19); and avoid exogenoussources of iodine, such as kelp, iodinesupplements, inorganic iodide, andiodinated contrast agents (may ex-acerbate the hyperthyroidism).

Table 3. Medications for Outpatient Treatment of HyperthyroidismFirst-Line Therapy Dose Side Effects

Beta-adrenergic blockade

Propranolol 10–40 mg QID CHF, asthma exacerbation

Atenolol 25–100 mg QD–BID CHF, asthma exacerbation

Metoprolol 25–100 mg BID–QID CHF, asthma exacerbation

Nadolol 40–160 mg QD CHF, asthma exacerbation

Antithyroid medications

Methimazole 5–120 mg QD Cutaneous reactions; increased ALP; agranulocytosis 0.2%–0.4% (dose-related)

Propylthiouracil 50–300 mg TID–QID Cutaneous reactions; increased AST/ALT; liver failure; agranulo-cytosis 0.2%–0.4% (not dose-related); ANCA-positive vasculitis

Radioactive iodine 10–30 mCi Causes hypothyroidism in 3–6 months; may acutely exacerbate hyperthyroidism; contraindicated with severe ophthalmopathy; contraindicatedin pregnancy and nursing

Ancillary Therapy Dose Notes

Potassium iodine (SSKI) 5 drops QID Acutely reduces thyroid hormone release; use before thyroidectomy for Graves disease; do not use before radioactive iodine therapy

Lithium 300 mg QID Reduces thyroid hormone release

Cholestyramine 1–2 g BID Binds thyroid hormone in the intestines

Nonsteroidal anti-inflammatory Variable doseing according Use to treat subacute thyroiditisdrugs to specific agent chosen

Glucocorticoids Prednnisone 20–40 mg daily Use to treat severe subacute for 2–4 wk thyroiditis

ALP = alkaline phosphatase; ALT = alanine transaminase; ANCA = antineutrophil cytoplasmic antibody; AST = aspartate transaminase; BID = twice daily; CHF = congestive heart failure; QD = once daily; QID = 4 times daily; SSKI = super-saturated potassium iodide; TID = 3 times daily.


21. Nakamura H, Noh JY,Itoh K, et al. Compar-ison of methimazoleand propylthiouracilin patients with hy-perthyroidismcaused by Graves’disease. J Clin En-docrinol Metab.2007;92:2157-62.[PMID: 17389704]

22. Abraham P, AvenellA, Watson WA, ParkCM, Bevan JS. An-tithyroid drug regi-men for treatingGraves’ hyperthy-roidism. CochraneDatabase Syst Rev.2005:CD003420.[PMID: 15846664]

23. Benker G, ReinweinD, Kahaly G, et al. Isthere a methimazoledose effect on re-mission rate inGraves’ disease? Re-sults from a long-term prospectivestudy. The EuropeanMulticentre TrialGroup of the Treat-ment of Hyperthy-roidism with Antithyroid Drugs.Clin Endocrinol(Oxf ). 1998;49:451-7.[PMID: 9876342]

24. Rittmaster RS, Ab-bott EC, Douglas R,et al. Effect of methi-mazole, with orwithout L-thyroxine,on remission rates inGraves’ disease. JClin EndocrinolMetab.1998;83:814-8.[PMID: 9506733]

25. Maugendre D, GatelA, Campion L, et al.Antithyroid drugsand Graves’ dis-ease–prospectiverandomized assess-ment of long-termtreatment. Clin En-docrinol (Oxf ].1999;50:127-32.[PMID: 10341866]

26. McDermott MT, Kidd GS, Dodson LEJr, Hofeldt FD. Radioiodine-inducedthyroid storm. Casereport and literaturereview. Am J Med.1983;75:353-9.[PMID: 6349350]

27. Cooper DS. Antithy-roid drugs in themanagement of patients with Graves’ disease: an evidence-based approach to thera-peutic controversies. J Clin EndocrinolMetab. 2003;88:3474-81. [PMID: 12915620]

28. Burch HB, Wartofsky L. Life-threatening thy-rotoxicosis. Thyroidstorm. EndocrinolMetab Clin NorthAm. 1993;22:263-77.[PMID: 8325286]


inhibit thyroid hormone synthesisand lower thyroid hormone levelsin patients with Graves disease,toxic multinodular goiter, and toxicadenoma (20). Both agents aregenerally quite effective (21), butmethimazole should be used be-cause of the potential for hepaticfailure with PTU (3). The optimalduration of methimazole therapy isusually 12–18 months, after whichit is tapered or discontinued if thepatient is asymptomatic and theTSH level is normal (3, 22). WhenGraves disease recurs after discon-tinuation of antithyroid medica-tion, which it does in about 50% of cases (20, 23–25), clinicians usu-ally recommend treatment with adrenergic blockers, radioactive iodine (I-131), or surgery. How-ever, methimazole can be restartedand maintained at low doses formore prolonged periods in patientswho prefer this choice (3).

Antithyroid medications also effec-tively lower thyroid hormone levelsin patients with toxic multinodulargoiter or a toxic adenoma, butmedical therapy does not result inpermanent remission. Therefore,treatment with I-131 or thyroidec-tomy is the preferred primary treat-ment choice for these disorders.Nonetheless, long-term, low-dosemethimazole therapy is reasonablefor patients who choose this optionand agree to frequent monitoring(3). When patients are treated withI-131 or thyroidectomy, antithyroidmedications are often prescribed tocontrol the hyperthyroidism beforetreatment and to reduce the risk forthyroid storm after treatment (3,26–29). Drugs used for this pur-pose should be discontinued 7 daysbefore I-131 treatment to preventthem from reducing the effective-ness of the treatment.

Antithyroid medications should notbe used in patients with low RAIUhyperthyroidism because it tends tobe self-limited and often respondsto nonsteroidal anti-inflammatory

medications, beta-adrenergic blockers, or glucocorticoid therapy(30). One exception is amiodarone-induced hyperthyroidism, whichmay respond to antithyroid medications (4, 5).

Minor drug side effects with methi-mazole and PTU include rash andabnormal results on liver tests,cholestatic changes with methima-zole (alkaline phosphatase), and he-patocellular enzyme elevations withPTU (aspartate transaminase, ala-nine transaminase). Because PTUcan cause severe hepatocellular dam-age with liver failure (31, 32), in2009 the U.S. Food and Drug Ad-ministration issued an alert advisingclinicians to use methimazole in-stead of PTU, except in thyroidstorm, cases of methimazole allergy,and in pregnant women in the firsttrimester (3, 32). When given towomen in early pregnancy, methi-mazole has been reported to be asso-ciated with absence of a portion ofscalp skin at birth (aplasia cutis) anda congenital blockage at the back ofthe nasal passage by abnormal boneor soft tissue (choanal atresia).Agranulocytosis is a potentially life-threatening disorder that occurs withboth drugs in about 0.2%–0.4% ofpatients (33, 34), most often withinthe first few months of treatment; itoccurs more commonly in patientsreceiving high doses (>40 mg/d) of methimazole (35, 33, 36) but isnot dose-related in patients takingPTU (35). PTU also causes moreantineutrophil cytoplasmic antibody–positive vasculitis (37, 38).

When should clinicians consider I-131 as primary therapy forhyperthyroidism?Because of its effectiveness andoverall safety, I-131 is 1 of the 3 pri-mary treatment options for Gravesdisease (3, 39). It is also a goodchoice for this disorder in patientswho do not have remission with an-tithyroid medications (3). It achievesremission in approximately 90% ofpatients with Graves disease.


29. Langley RW, BurchHB. Perioperativemanagement of thethyrotoxic patient.Endocrinol MetabClin North Am.2003;32:519-34.[PMID: 12800544]

30. Fatourechi V,Aniszewski JP, Fa-tourechi GZ, Atkin-son EJ, Jacobsen SJ.Clinical features andoutcome of suba-cute thyroiditis in anincidence cohort:Olmsted County,Minnesota, study. J Clin EndocrinolMetab. 2003;88:2100-5. [PMID: 12727961]

31. Williams KV, Nayak S,Becker D, Reyes J,Burmeister LA. Fiftyyears of experiencewith propylthiouracil-associated hepato-toxicity: what havewe learned? J Clin EndocrinolMetab. 1997;82:1727-33. [PMID: 9177371]

32. Cooper DS, RivkeesSA. Putting propylth-iouracil in perspec-tive. J Clin Endocrinol Metab.2009;94:1881-2.[PMID: 19401361]

33. Meyer-Gessner M,Benker G, Lederbo-gen S, Olbricht T,Reinwein D. Antithy-roid drug-inducedagranulocytosis: clin-ical experience withten patients treatedat one institutionand review of the lit-erature. J EndocrinolInvest. 1994;17:29-36. [PMID: 7516356]

34. Sheng WH, HungCC, Chen YC, et al.Antithyroid-drug-induced agranulocy-tosis complicated bylife-threatening in-fections. QJM.1999;92:455-61.[PMID: 10627862]

35. Cooper DS, Gold-minz D, Levin AA, etal. Agranulocytosisassociated with an-tithyroid drugs. Ef-fects of patient ageand drug dose. AnnIntern Med.1983;98:26-9.[PMID: 6687345]

36. Takata K, Kubota S,Fukata S, et al. Methimazole-induced agranulocy-tosis in patients withGraves’ disease ismore frequent withan initial dose of 30 mg daily thanwith 15 mg daily.Thyroid. 2009;19:559-63. [PMID: 19445623]


Hypothyroidism is the main side effect and occurs in virtuallyall patients for whom treatment iseffective. Most patients becomehypothyroid within 3–6 monthsof I-131 therapy. Sialadenitis isan occasional side effect from uptake by the salivary glands.Worsening of preexisting Gravesorbitopathy is now a well-recognized potential complicationof I-131 treatment (19, 40–43).Patients with mild orbitopathycan receive I-131 but may benefitfrom pretreatment with glucocor-ticoids. Patients with moderate to severe orbitopathy shouldchoose another option (3). Treat-ment does not seem to increasecancer mortality. Although therewas a small increase in thyroidcancer in I-131-treated patients,this may be related to intrinsicthyroid disease (44). Becausemost patients with Graves disease become hypothyroid within 3–6 months of I-131 therapy, this outcome should be anticipated so it can bepromptly recognized and treatedbefore the onset of severe hypothyroidism.

For toxic multinodular goiters andtoxic adenomas, I-131 is consid-ered 1 of 2 preferred options forprimary therapy (3). Hypothy-roidism is the main side effect of I-131 therapy in these 2 condi-tions but still is only present in50%–75% of patients, in contrastto nearly 100% of patients withGraves disease.

Thyroid hormone levels often increase transiently in the first1–2 weeks after I-131 administra-tion, regardless of diagnosis. Thisincrease can cause worseningsymptoms and has even been re-ported to precipitate thyroidstorm in severely hyperthyroid individuals (26, 27). Experts rec-ommend that clinicians pretreatvery symptomatic patients orthose who have free T4 or FT4I

levels that exceed the upper limit of the reference range morethan 2-fold with beta-adrenergicblockade (3), methimazole (3), or both for up to a month beforeI-131 therapy. However, methi-mazole should be discontinued 7 days before I-131 treatment because otherwise it can reduce the effectiveness of this therapy.

Pregnancy is an absolute contra-indication to I-131 treatment (15,16), and women of childbearingpotential should have a negativepregnancy test before receiving thistreatment. This therapy is not effec-tive in low RAIU hyperthyroidismand should not be used (47).

When should clinicians considerthyroidectomy as primary therapy?Thyroidectomy can be considered asprimary therapy for patients withhigh RAIU hyperthyroidism and in refractory cases of amiodarone-induced hyperthyroidism. Thyroidec-tomy is most often recommendedfor hyperthyroid patients who havethyroid nodules and are suspectedto have cancer and in patients whocannot tolerate or who refuse alter-native forms of therapy. Because I-131 is contraindicated duringpregnancy, surgery may also beconsidered in pregnant women inthe second trimester whose hyper-thyroidism is not controlled withantithypertensive medications. Sur-gery may also be appropriate forpatients who do not achieve remis-sion with antithyroid medications,particularly those with moderateto severe Graves orbitopathy (3).

Clinicians should use methimazoleto induce euthyroidism before sur-gery (3). Patients with Graves disease, but not those with toxicmultinodular goiters or toxic ade-nomas, should also receive oralpotassium iodide during the weekbefore surgery (3) to further reducethyroid hormone levels and to re-duce the vascularity of the thyroid


37. Noh JY, Asari T,Hamada N, Makino F,Ishikawa N, Abe Y, etal. Frequency of ap-pearance ofmyeloperoxidase-antineutrophil cyto-plasmic antibody(MPO-ANCA) inGraves’ disease pa-tients treated withpropylthiouracil andthe relationship be-tween MPO-ANCAand clinical manifes-tations. Clin En-docrinol (Oxf ).2001;54:651-4.[PMID: 11380496]

38. Chen YX, Yu HJ, Ni LY, et al. Propylthiouracil-associated antineu-trophil cytoplasmicautoantibody-positive vasculitis:retrospective studyof 19 cases. JRheumatol. 2007;34:2451-6. [PMID: 17985400]

39. Abraham-Nordling M, Wallin G, Lundell G,Torring O. Thyroidhormone state andquality of life atlong-term follow-upafter randomizedtreatment of Graves’disease. Eur J En-docrinol. 2007;156:173-9. [PMID: 17287406]

40. Bartalena L, Mar-cocci C, Bogazzi F,et al. Relation be-tween therapy forhyperthyroidism andthe course of Graves’ophthalmopathy. N Engl J Med.1998;338:73-8.[PMID: 9420337]

41. Tallstedt L, Lundell G, Tørring O, et al. Oc-currence of ophthal-mopathy after treat-ment for Graves’hyperthyroidism.The Thyroid StudyGroup. N Engl J Med.1992;326:1733-8.[PMID: 1489388]

42. Träisk F, Tallstedt L,Abraham-Nordling M, et al; Thyroid StudyGroup of TT 96. Thy-roid-associated ophthalmopathy af-ter treatment forGraves’ hyperthy-roidism with antithy-roid drugs or iodine-131. J Clin En-docrinol Metab.2009;94:3700-7.[PMID: 19723755]

43. Acharya SH, Avenell A, Philip S, Burr J, BevanJS, Abraham P. Ra-dioiodine therapy(RAI) for Graves’ dis-ease (GD) and theeffect on ophthal-mopathy: a system-atic review. Clin En-docrinol (Oxf ).2008;69:943-50.[PMID: 18429949]


gland. Outcomes are best when ahigh-volume thyroid surgeon does the procedure (3, 48). Mostpatients will be rendered hypothy-roid by this treatment, dependingon the extent of surgery, and shouldbe started on replacement doses oflevothyroxine (1.7 µg/kg per d) be-fore discharge from the hospital(3). Thyroidectomy is not indicatedfor low RAIU hyperthyroidism(47) other than for occasional pa-tients with refractory amiodarone-induced hyperthyroidism.

How should clinicians monitorpatients who are being treated forhyperthyroidism?Clinicians should do a baselinecomplete blood count (CBC) witha differential white blood cell (WBC) count and a liver panel, regardless ofwhich treatment is chosen but par-ticularly before initiating antithyroidmedications (3). Baseline studies areimportant because hyperthyroidismitself and the various treatments canall cause abnormalities. The moni-toring strategy after treatmentshould differ depending on whichtreatment is chosen. After successfultreatment of any type, however, oncepatients are euthyroid (with orwithout levothyroxine-replacementtherapy) they should be assessedclinically and have serum TSHmeasured (with or without measure-ment of free T4 ) every 6–12 monthsfor the remainder of their lives.

When antithyroid medications arethe treatment choice, patients should be advised to discontinue the med-ications and notify their provider ifthey develop signs or symptoms ofagranulocytosis (fever, sore throat),liver injury (jaundice, dark urine,acolic stools, pruritus, abdominalpain, nausea, vomiting), or vasculitis(fatigue, arthralgias) (3). The clini-cian should order a repeated CBCwith a differential WBC if patientsreport fever or pharyngitis and aliver profile if they report symptomsof liver injury (3). Once symptomsof hyperthyroidism have resolved

and test results are within the refer-ence range, the clinician should discontinue the beta-adrenergicblocker, reduce the dose of antithy-roid medication, and continue clini-cal and laboratory assessments every3–6 months. If the serum TSH isnormal after 12–18 months on re-duced doses of antithyroid medica-tion, the clinician can taper or stopthe medication to determinewhether the patient has achievedremission (3, 22). Some experts rec-ommend measuring TRAb at thistime, because a normal level indi-cates a greater likelihood of remis-sion and predicts which patients canbe successfully weaned from the an-tithyroid medication (3, 46). If re-mission has not occurred, the clini-cian should consider treatment withI-131 or surgery, but a more pro-longed course of low-dose methi-mazole is reasonable if the patientprefers this approach (3).

Patients who receive radioactive iodine should have a repeated clin-ical assessment and laboratory testing 1–2 months after I-131 administration (3). Because serum TSH levels may remain suppressed for as long as 6 weeksafter chronically elevated T4 and T3levels decrease to or below the nor-mal range (47), it is important tomeasure both TSH and free T4levels in the first 1–3 months aftertherapy; during this time, hypothy-roidism can be characterized by either elevated TSH or low free T4levels. Accordingly, thyroid hor-mone–replacement therapy shouldbe started when either the free T4level becomes low or the serum TSH level becomes elevated. SerumTSH testing is recommended 6–8 weeks after thyroidhormone–replacement therapy isstarted, with dose adjustment at 6- to 8-week intervals until theTSH level is in the desired range.

After thyroidectomy for hyperthy-roidism, clinicians should start fullreplacement doses of levothyroxine


44. Ron E, Doody MM,Becker DV, Brill AB, etal. Cancer mortalityfollowing treatmentfor adult hyperthy-roidism. CooperativeThyrotoxicosis Therapy Follow-upStudy Group. JAMA.1998;280:347-55.[PMID: 9686552]

45. Sosa JA, BowmanHM, Tielsch JM,Powe NR, GordonTA, Udelsman R. Theimportance of sur-geon experience forclinical and econom-ic outcomes fromthyroidectomy. AnnSurg. 1998;228:320-30. [PMID: 9742915]

46. Feldt-Rasmussen U,Schleusener H,Carayon P. Meta-analysis evaluationof the impact of thy-rotropin receptor an-tibodies on longterm remission aftermedical therapy ofGraves’ disease. J Clin EndocrinolMetab. 1994;78:98-102. [PMID: 8288723]

47. Uy HL, Reasner CA,Samuels MH. Patternof recovery of thehypothalamic-pituitary-thyroid axisfollowing radioactiveiodine therapy in pa-tients with Graves’disease. Am J Med.1995;99:173-9.[PMID: 7625422]

48. Surks MI, Ortiz E,Daniels GH, et al.Subclinical thyroiddisease: scientific re-view and guidelinesfor diagnosis andmanagement. JAMA.2004;291:228-38.[PMID: 14722150]

49. Gharib H, Tuttle RM,Baskin HJ, Fish LH,Singer PA, McDer-mott MT. Subclinicalthyroid dysfunction:a joint statement onmanagement fromthe American Asso-ciation of Clinical En-docrinologists, theAmerican ThyroidAssociation, and theEndocrine Society. J Clin EndocrinolMetab. 2005;90:581-5; discussion 586-7.[PMID: 15643019]

50. Sawin CT, Geller A,Wolf PA, et al. Lowserum thyrotropinconcentrations as arisk factor for atrialfibrillation in olderpersons. N Engl JMed. 1994;331:1249-52. [PMID: 7935681


(1.7 µg/kg daily) (3) at or beforehospital discharge. Serum TSHshould be tested 6–8 weeks later,with the dose adjusted at 6- to 8-week intervals until the level is inthe desired range.

What is subclinical hyper -thyroidism, and what are theindications for treatment?Subclinical hyperthyroidism is lowserum TSH levels combined withT4 and T3 levels within the serumreference ranges (48, 49). Many pa-tients are asymptomatic, or hyper-thyroidism symptoms, if present,are usually mild. The RAIU is typi-cally within the reference range,and thyroid scan findings are con-sistent with the underlying cause(diffuse uptake for Graves disease,patchy uptake for toxic multinodu-lar goiter, and isolated uptake fortoxic adenoma).

Although there is agreement aboutthe definition of subclinical hyper-thyroidism, there is substantiallyless agreement about how and evenwhether to treat it (48, 49). Expertsdisagree because most patients haveonly a few mild symptoms, andTSH levels often return to normalwithout treatment. They agree thatpatients with TSH levels <0.1 mU/L or those who are convincinglysymptomatic should be treated (48, 49). Debate on management of patients with levels ≥0.1 mU/Lbut that are still lower than the reference range continues (48, 49),although recent studies have raisedconcern about potential negativeeffects of hyperthyroidism on theheart (50, 51), bones (52, 53), andcentral nervous system. For exam-ple, data now indicate an increasedrisk for atrial fibrillation when theTSH level is < 0.3 mU/L (50).When patients with subclinical hy-perthyroidism have symptoms thatmay be caused by hyperthyroidismbut are too vague for the clinicianto be confident about their cause,some experts recommend startingan antithyroid medication and

then deciding whether to continuebased on whether symptoms im-prove as the TSH level becomesnormal.

How does a clinician recognizeand treat thyroid storm?Thyroid storm, which some peoplecall “thyroid crisis,” is a life-threatening condition characterized by exagger-ated manifestations of thyrotoxico-sis. It usually occurs in patientswho have unrecognized or inade-quately treated thyrotoxicosis combined with a precipitatingevent, such as thyroid or other surgery, infection, or trauma. Also,radioiodine therapy for severe hyperthyroidism may occasionallyprecipitate thyroid storm. Fever>102° F is the cardinal manifesta-tion of this condition. Tachycardiais usually present, and tachypnea iscommon. Cardiac arrhythmias,congestive heart failure, and is-chemic heart symptoms developfrequently. Nausea, vomiting, diar-rhea, and abdominal pain are alsocommon features. Central nervoussystem manifestations include hy-perkinesis, psychosis, and coma (28).

Serum total and free T4 and totaland free T3 levels are usually elevated, and the serum TSH level is unde-tectable. Other common laboratoryabnormalities include anemia,leukocytosis, hyperglycemia, azote -mia, hypercalcemia, and elevatedliver enzymes.

Under most circumstances, theclinician must diagnose thyroidstorm on the basis of suspiciousbut nonspecific clinical findings.Serum thyroid hormone levels are elevated in this disorder, butwaiting for test results will delaytherapy that could be lifesaving if thyroid storm is present. Furthermore, thyroid hormonelevels do not reliably distinguishpatients with thyroid storm fromthose with uncomplicated thyro-toxicosis. Therefore, clinical fea-tures are the key to this diagnosis,


51. Gammage MD, ParleJV, Holder RL,Roberts LM, HobbsFD, Wilson S, et al.Association betweenserum free thyroxineconcentration andatrial fibrillation.Arch Intern Med.2007;167:928-34.[PMID: 17502534]

52. Foldes J, Tarjan G,Szathmari M, Varga F,Krasznai I, Horvath C.Bone mineral densi-ty in patients withendogenous sub-clinical hyperthy-roidism: is this thyroid status a riskfactor for osteoporo-sis? Clin Endocrinol(Oxf ). 1993;39:521-7.[PMID: 8252739]

53. Bauer DC, Ettinger B,Nevitt MC, Stone KL;Study of Osteo-porotic Fractures Re-search Group. Riskfor fracture inwomen with lowserum levels of thyroid-stimulatinghormone. Ann In-tern Med. 2001;134:561-8. [PMID: 12803168]


and a scoring system is availableto help clinicians determine when to make the diagnosis (28)(Table 4).

The immediate goals of therapy areto decrease thyroid hormone syn-thesis with methimazole or PTU;inhibit thyroid hormone releasewith sodium or potassium iodide;reduce the heart rate with a beta-blocker, such as esmolol, metopro-lol, or propranolol or a calciumchannel blocker, such as diltiazem;support the circulation with gluco-corticoids, IV fluids, oxygen, andcooling; and treat the precipitating

condition (28). The Box (Treat-ment of Thyroid Storm) providesmore detailed information abouttherapy.

When should patients behospitalized?Hyperthyroid patients should behospitalized when thyroid storm ispresent, impending, or suspected.When thyroid storm was first de-scribed, the acute mortality ratewas nearly 100%. Although theprognosis today is much betterwith aggressive therapy, mortalityremains around 20%.

Table 4. Thyroid Storm Scoring System*Feature Score

Fever, ° F

99–99.9 5100–100.9 10101-101.9 15102-102.9 20103-103.9 25>104 30

Central nervous system agitationAbsent 0Mild 10Moderate 20Severe 30

Cardiac–pulse, bpm99–109 5110–119 10120–129 15130–139 20≥140 25Atrial fibrillation 10

Cardiac–CHFAbsent 0Mild (edema) 5Moderate (rales) 10Severe (pulmonary edema) 15

Gastrointestinal signsAbsent 0N, V, D, Pain 10Jaundice 20

Precipitant historyAbsent 0Present 10

*Thyroid storm score <25 = unlikely; 25–44 = suggestive; >45 = likely.



Treatment of Thyroid Storm1. Decrease thyroid hormone synthesis

• Propylthiouracil (oral, rectal, nasogastric [NG] tube): 600–1200 mg daily, divided doses• Methimazole (oral, rectal, NG tube, intravenous [IV]): 60–120 mg daily, divided doses

2. Inhibit thyroid hormone release• Sodium iodide (IV): 1 g over 24 h• Potassium iodide (oral), 5 drops 4 times/d (super-saturated potassium iodide)

3. Reduce heart rate• Esmolol (IV): 500 mg over 1 min, then 50–100 mg/kg/min• Metoprolol (IV): 5–10 mg every 2–4 h• Propranolol (oral): 60-80 mg every 4 h• Diltiazem (IV): 0.25 mg/kg over 2 min, then infusion of 10 mg/min (oral): 60–90 mg

every 6–8 h4. Support circulation

• Glucocorticoids in stress doses• Fluids, oxygen, cooling

5. Treat precipitating cause

present, impending, or suspected.Some published guidelines suggestco-management with an endocri-nologist in all cases of hyperthy-roidism (1). Clinicians should consider consulting an ophthalmol-ogist when the patient has doublevision; impaired visual acuity, visual fields, or color vision; signifi-cant eye discomfort; proptosis >22 mm; or extraocular muscle dysfunction.

When should clinicians considerconsulting an endocrinologist orophthalmologist?Clinicians should consider consult-ing an endocrinologist after diagnosis for help developing anoptimal management plan; whenunexpected events occur; whenthere are treatment complications;when significant Graves eye diseaseis present; if the patient is preg-nant; and when thyroid storm is

beneficiaries. CMS named thisprogram the Physician Quality Re-porting Initiative (PQRI). Eligibleprofessionals who meet the criteriafor satisfactory submission of datafor services can earn incentive payments. The 2012 PQRI consistsof 318 quality measures; however,none specifically apply to personswith hyperthyroidism.

What measures do stakeholdersuse to evaluate the quality of care for patients withhyperthyroidism?Federal legislation passed in 2006required the Centers for Medicare& Medicaid Services (CMS) tocreate a physician reporting systemfor quality measures regarding cov-ered services furnished to Medicare

PracticeImprovement

Treatment... Hyperthyroidism associated with high or normal RAIU usually re-quires treatment. Clinicians should inform patients about the benefits and risksof each possible therapy, and patients and clinicians should jointly decide onthe preferred treatment. Graves disease can be treated with antithyroid med-ications, I-131, or thyroidectomy. Toxic multinodular goiter and toxic adenomaare usually treated with I-131 or thyroidectomy, but antithyroid medicationsare used to improve thyroid hormone levels before definitive treatment. Hyper-thyroidism associated with low RAIU is usually treated with measures directedat the underlying cause or simply monitored, because these conditions are of-ten transient.



Inthe

C linic

Tool KitIn the Clinic

Hyperthyroidism

PIER Modulehttp://pier.acponline.org/physicians/diseases/d175/d175.htmlPIER module on hyperthyroidism from the

American College of Physicians. PIER modulesprovide evidence-based, updated information oncurrent diagnosis and treatment in an electronicformat designed for rapid access at the point ofcare.

Patient Informationwww.annals.org/site/patientinformation/patientinformation.xhtmlPatient information that appears on the following

pages for duplication and distribution topatients.

www.nlm.nih.gov/medlineplus/thyroiddiseases.htmlInformation on thyroid-associated diseases, from

the National Institutes of Health’sMedlinePLUS.

www.hormone.org/Resources/thyroid-disorders.cfmwww.hormone.org/Spanish/index.cfmPatient resources on thyroid disorders, including

information in both English and Spanish, fromthe Hormone Foundation.

www.uptodate.com/contents/patient-information-hyperthyroidism-overactive-thyroid-beyond-the-basicsInformation for patients on hyperthyroidism, from

UpToDate.

Clinical Guidelineswww.aace.com/sites/default/files/HyperGuidelines2011.pdfPractice guidelines for the evaluation and treatment

of hyperthyroidism and hypothyroidism, from theAmerican Association of ClinicalEndocrinologists in May 2011.

www.annals.org/content/140/2/125.fullwww.annals.org/content/140/2/128.fullU.S. Preventive Services Task Force

recommendation statement on screening forthyroid disease, and a summary of the evidence,published in Annals of Internal Medicine inJanuary 2004.

http://jcem.endojournals.org/content/92/8_suppl/s1.fullPractice guidelines on the management of thyroid

dysfunction during pregnancy and thepostpartum period, from the Endocrine Societyin August 2007.

Diagnostic Tests and Criteriahttp://pier.acponline.org/physicians/diseases/d175/tables/d175-tlab.htmlTable listing laboratory and other studies for

thyrotoxicosis.

3 July 2012Annals of Internal MedicineIn the ClinicITC1-14© 2012 American College of Physicians

Clinical Endocrinologists have re-cently published evidence-basedguidelines for management of hyperthyroid patients (3). Theseguidelines are incorporated intothis report.

What do professionalorganizations recommendregarding care of patients withhyperthyroidism?The American Thyroid Associationand American Association of


In the ClinicAnnals of Internal Medicine

Pati

ent

Info

rmat

ion

THINGS YOU SHOULDKNOW ABOUTHYPERTHYROIDISM

What is hyperthyroidism?• A disorder that occurs when the thyroid, a butterfly-

shaped gland located in the neck, makes excessthyroid hormones.

• Thyroid hormones regulate how your body uses andstores energy.

• Having too much of these hormones can speed up everyfunction of your body (called the “metabolic rate”).

• About 1% of the U.S. population has this condition,which is sometimes called “overactive thyroid.”

• It affects women, particularly between the ages of20 and 40, more commonly than men.

What causes hyperthyroidism?• Graves disease (an autoimmune disease).• Noncancerous thyroid nodules or lumps.• Excess iodine consumption.• Overmedication with synthetic thyroid hormone for

underactive thyroid.• Noncancerous tumor of the pituitary gland (rare).• Thyroiditis (inflammation of the thyroid gland that

causes stored hormones to leak out into the body).

What are common symptoms?• Feeling too hot, increased sweating.• Muscle weakness, trembling hands.• Rapid heartbeat, tiredness, fatigue.• Weight loss, diarrhea, or frequent bowel movements.• Painful urination and feeling an urgent need to

urinate frequently.• Menstrual irregularities and infertility.• Eye irritation or discomfort.

How is it diagnosed?• Your doctor will perform a careful physical

examination and order blood tests to measure yourhormone levels.

• Hyperthyroidism is diagnosed when blood tests showthat certain hormones levels are abnormal.

• Your doctor may order a radioactive iodine uptake test to identify what is causing yourhyperthyroidism.

• A thyroid scan may be ordered to check the shapeand size of your thyroid gland, and to see if anynodules are present.

How is it treated?• Treatment depends on the cause of the

hyperthyroidism; your age, physical condition, andpreferences; and the severity of the condition.

• Medications may be used to reduce the amount ofhormone your thyroid gland makes.

• Beta-blockers can help control your symptoms,including rapid heart rate, tremors, anxiety, and heatintolerance.

• Radiation to destroy the thyroid with radiation,called radioiodine ablation, provides a permanenttreatment.

• The thyroid may be removed surgically.

For More Information

www.thyroid.org/patients/patient_brochures/hyperthyroidism.htmlwww.thyroid.org/patients/faqs/hyperthyroidism.htmlInformation and answers to frequently asked questions on

hyperthyroidism, from the American Thyroid Association.

www.endocrine.niddk.nih.gov/pubs/Hyperthyroidism/www.endocrine.niddk.nih.gov/pubs/graves/Information on hyperthyroidism and Graves disease from the

National Institute of Diabetes and Digestive and KidneyDiseases.


CME Questions

3 July 2012Annals of Internal MedicineIn the ClinicITC1-16© 2012 American College of Physicians

Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP, accessed at http://www.acponline.org/products_services/mksap/15/?pr31). Go to www.annals.org/intheclinic/

to complete the quiz and earn up to 1.5 CME credits, or to purchase the complete MKSAP program.

1. A 38-year-old woman is evaluated for a 3-month history of increased sweating,increased appetite, and a 7.3-kg (16-lb)weight loss. The patient also reports a 4-month history of amenorrhea, beforewhich she felt “completely healthy.”Medical history is otherwise unremarkable,and she takes no medications.

Physical examination shows a thin, restlesswoman with smooth, fine, moist skin andfine hair. Blood pressure is 108/60 mm Hg,pulse rate is 96/min, respiration rate is14/min, and BMI is 18.1. Mild lid lag isnoted, but no proptosis, diplopia, orconjunctival injection is detected. Herthyroid gland is soft and enlargedapproximately 2-fold. There is a mild, finetremor of the outstretched hands. Reflexesare brisk. Laboratory results are as follows:thyroid-stimulating hormone, 2.4 µU/mL(2.4 mU/L); thyroxine (T4), free; 2.7 ng/dL(34.8 pmol/L); and triiodothyronine (T3),total, 387 ng/dL (5.96 nmol/L).

Which of the following is the mostappropriate next test for this patient?

A. MRI of the pituitary glandB. Thyroid anti–peroxidase antibody testC. Thyroid radioactive iodine uptake

determinationD. Thyroid scanE. Thyroid-stimulating immunoglobulin

measurement

2. A 35-year-old woman is evaluated fordiaphoresis, a 3.6-kg (8.0-lb) weight loss,and elevated blood glucose levels 6 weeksafter delivering her second child. She has an18-year history of type 1 diabetes mellitus,which has been successfully treated with aninsulin pump for the past 8 years. Herglycemic control during this period has beenoutstanding, with an average hemoglobinA

1cvalue of 6.2%. Although her diabetes

was well-controlled during most of therecent pregnancy, the insulin dosage neededto be increased by almost 50% to maintainglycemic control. Postpartum, the patientreduced the insulin dosage to herprepregnancy baseline requirements, butthis step has been inadequate to controlher blood glucose level.

On physical examination, vital signs arenormal. Tachycardia, tremor, hyperreflexia,and a wide pulse pressure are noted.

Results of a complete blood count andmetabolic panel are normal.

Measurement of which of the followingis most likely to diagnose the cause ofthe deteriorating glucose control?

A. Antitransglutaminase antibody titersB. Hemoglobin A

1cvalue

C. Postprandial glucose levelD. Thyroid-stimulating hormone levelE. Urine free cortisol level

3. An 18-year-old woman is evaluated fortachycardia, nervousness, decreasedexercise tolerance, and weight loss of 6 months’ duration. She has otherwisebeen healthy. Her sister has Gravesdisease. She takes no medications.

On physical examination, blood pressureis 128/78 mm Hg, pulse rate is 124/min,respiration rate is 16/min, and BMI is19.5. There is no proptosis. Anexamination of the neck reveals asmooth thyroid gland more than 1.5 times the normal size. Cardiacexamination reveals regular tachycardiawith a grade 2/6 early systolic murmur atthe base. Her lungs are clear toauscultation. Laboratory results revealthe following: human chorionicgonadotropin, negative; thyroid-stimulating hormone, <0.01 µU/mL (0.01 mU/L); thyroxine (T4), free, 5.5 ng/dL (71.0 pmol/L); and triiodothyronine (T3),free, 9.1 ng/L (14 pmol/L).

Which of the following is the mostappropriate treatment regimen at thistime?

A. Atenolol onlyB. Methimazole onlyC. Atenolol and methimazoleD. Radioactive iodine and methimazole

4. A 55-year-old man is evaluated for a 4-month history of weight loss, heatintolerance, tremor, and hyperdefecationand a 1-week history of dry eyes that aresensitive to light and frequently injected.He reports no blurred or double visionbut does relate having been previouslydiagnosed with a “thyroid condition” andhaving a severe allergic reaction tomethimazole therapy. The patientcurrently takes no medications.

On physical examination, blood pressureis 140/88 mm Hg, pulse rate is 120/min,respiration rate is 18/min, and BMI is 22.Pupils are equal, round, and reactive tolight and accommodation; extraocularmovements are intact. Mild bilateralconjunctival injection and periorbitaledema are noted. There is no chemosis,but some slight lid lag and proptosis arepresent. Examination of the neck revealsa smooth thyroid gland that is 3 times itsnormal size. Cardiac examination showstachycardia and a regular rhythm. Thereis a 3+ upper extremity tremor bilaterally.

Laboratory studies show a serum thyroid-stimulating hormone level of 0.01 µU/mL(0.01 mU/L) and a serum free thyroxine(T4) level of 3.8 ng/dL (49.0 pmol/L).

Which of the following is the mostappropriate treatment for this patient?

A. Immediate thyroidectomyB. Orbital decompression surgeryC. Prednisone and radioactive iodine

ablationD. Radioactive iodine ablation alone

5. A 76-year-old woman is reevaluatedafter abnormal results on thyroidfunction tests performed 2 weeks ago.The patient feels well. She has a historyof hypertension, atrial fibrillation,gastroesophageal reflux disease, anddepression. Current medications aremetoprolol, amiodarone, warfarin,omeprazole, and sertraline.

On physical examination, blood pressure is125/65 mm Hg, pulse rate is 83/min, andrespiration rate is 15/min. The thyroidgland is smooth and of normal size.Cardiac examination reveals an irregularlyirregular rhythm. Deep tendon reflexes arenormal. Laboratory results are as follows:thyroid-stimulating hormone, 6.5 µU/mL(6.5 mU/L); thyroxine (T4), free, 2.4 ng/dL(31.0 pmol/L); and triiodothyronine (T3),free, 0.8 ng/L (1.2 pmol/L).

Which of the following medications ismost likely responsible for the laboratoryresults?

A. AmiodaroneB. MetoprololC. OmeprazoleD. Sertraline


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