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Hyperthyroidism

Article  in  Annals of Internal Medicine · July 2012

DOI: 10.7326/0003-4819-157-1-20120703-01001 · Source: PubMed

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 In theClinic
In the Clinic

Hyperthyroidism
Screening 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 Writer The content of In the Clinic is drawn from the clinical information and education
Michael T. McDermott, MD resources of the American College of Physicians (ACP), including PIER (Physicians’
Information and Education Resource) and MKSAP (Medical Knowledge and Self-
Section Editors Assessment Program). Annals of Internal Medicine editors develop In the Clinic
Deborah Cotton, MD, MPH from these primary sources in collaboration with the ACP’s Medical Education and
Darren Taichman, MD, PhD Publishing divisions and with the assistance of science writers and physician
Sankey Williams, MD writers. Editorial consultants from PIER and MKSAP provide expert review of the
content. Readers who are interested in these primary resources for more detail can
consult 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, and
treatment of hyperthyroidism.

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

© 2012 American College of Physicians

 yperthyroidism is a clinical state characterized by excessive serum

H concentrations of thyroxine (T4 ), triiodothyronine (T3 ), or both

with 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 the
term hyperthyroidism.

Hyperthyroidism is considered to be “overt” when a low serum TSH level

is associated with elevated serum levels of free or total T4 and/or free or
total T3. Hyperthyroidism is considered to be “subclinical” when a low
serum TSH level is associated with serum T4 and T3 levels that are within
the population reference range. Therefore, the terms overt and subclinical are
defined biochemically without reference to clinical features. Although
symptoms and signs are usually prominent in overt hyperthyroidism, they
may or may not be present in subclinical hyperthyroidism. The prevalence
of hyperthyroidism in the United States is estimated to be about
0.4%–1.2%, with approximately 40% of cases being overt and 60% being
1. Singer PA, Cooper DS, subclinical (1–3).
Levy EG, et al. Treat-
ment guidelines
for patients with hy-
perthyroidism and
hypothyroidism.
Screening
Standards of Care
Committee, Ameri-
Who has an elevated risk for have other medical conditions that
can Thyroid Associa- hyperthyroidism? may be caused or aggravated by
tion. JAMA.
1995;273:808-12. People at increased risk for hyper- hyperthyroidism, such as osteo-
[PMID: 7532241]
2. Hollowell JG,
thyroidism include those with porosis, supraventricular tachycar-
Staehling NW, Flan- diffuse or nodular goiters, type 1 dia, or atrial fibrillation. Screening
ders WD, et al. Serum
TSH, T(4), and thyroid
diabetes mellitus, other endocrine may also be more cost-effective
antibodies in the and nonendocrine autoimmune dis- in women older than 50 years of
United States popula-
tion (1988 to 1994): eases, and family histories of hyper- age (10), because 1 out of every
National Health and
Nutrition Examina-
thyroidism or hypothyroidism. 71 women in this age group has
tion Survey (NHANES Medications that increase the risk unsuspected but symptomatic
III). J Clin Endocrinol
Metab. 2002;87:489-
for hyperthyroidism include amio- hyperthyroidism or hypothy-
99. [PMID: 11836274] darone (4, 5), alpha-interferon (6), roidism that responds well to
3. Bahn RS, Burch HB,
Cooper DS, et al. Hy- interleukin-2 (7), lithium (8), and treatment. As a result, screening
perthyroidism and
other causes of thyro-
iodide (9). The iodinated contrast women over age 50 is recom-
toxicosis: manage- agents administered for imaging mended, especially because the
ment guidelines of
the American Thyroid studies also increase risk for hyper- TSH test that screens for hyper-
Association and thyroidism in individuals who have thyroidism also screens for hy-
American Association
of Clinical Endocri- preexisting autoimmune or nodular pothyroidism, a disorder that is
nologists. Thyroid
2011; 21:593-646).
thyroid disease. more common in this population.
[PMID: 21700562]
4. Newman CM, Price A, Should clinicians screen for If clinicians screen for
Davies DW, Gray TA,
Weetman AP. Amio- hyperthyroidism? hyperthyroidism, which test
darone and the thy-
roid: a practical guide
Screening for hyperthyroidism in should they use?
to the management the general population is not cost- Measuring serum TSH levels is the
of thyroid dysfunc-
tion induced by effective because of the low preva- best way to screen for hyperthy-
amiodarone therapy. lence of the disorder. It is prudent, roidism. Serum TSH becomes low
Heart. 1998;79:121-7.
[PMID: 9538302] however, to screen people who are in both overt and subclinical hyper-
5. Piga M, Serra A, Boi F,
Tanda ML, Martino E,
at high risk when they have the thyroidism because of negative
Mariotti S. Amiodarone- comorbid conditions, family history, feedback by elevated thyroid hor-
induced thyrotoxico-
sis. A review. Minerva or medication use described in the mone levels on the pituitary gland,
Endocrinol. previous section. Screening should and TSH assays are standardized,
2008;33:213-28.
[PMID: 18846027] also be considered in patients who accurate, and widely available.

© 2012 American College of Physicians ITC1-2 In the Clinic Annals of Internal Medicine 3 July 2012
 Screening... Screening for hyperthyroidism in the general population is not cost-
effective, but experts recommend screening with a test for serum TSH in persons
with diffuse or nodular goiters, type 1 diabetes mellitus, other endocrine and
nonendocrine autoimmune diseases, osteoporosis, supraventricular tachycardia, or
atrial fibrillation; in those with family histories of hyperthyroidism or hypothy-
roidism; in those taking amiodarone, alpha-interferon, interleukin-2, lithium, or
iodide; and in women older than 50 years of age.

CLINICAL BOTTOM LINE

Diagnosis
What symptoms should prompt What physical examination
clinicians to consider findings indicate possible
hyperthyroidism? hyperthyroidism?
Symptoms that suggest hyper- The physical signs often identified 6. Dumoulin FL, Leifeld
L, Sauerbruch T,
thyroidism include nervousness, in hyperthyroid patients include Spengler U. Autoim-
munity induced by
increased sweating, heat intoler- tachycardia; goiter; skin changes; interferon-alpha ther-
ance, palpitations, fatigue, weight tremor; thyroid bruit; and eye signs, apy for chronic viral
hepatitis. Biomed
loss, tachycardia, dyspnea, weak- such as stare and lid lag. Some fea- Pharmacother.
ness, leg edema, eye symptoms, tures of the physical examination 1999;53:242-54.
[PMID: 10424246]
emotional lability, and frequent may also be useful in determining 7. Vialettes B, Guillerand
MA, Viens P, et al. Inci-
defecation without an increase in the cause of hyperthyroidism. The dence rate and risk
stool weight (hyperdefecation). diagnosis of Graves disease is sug- factors for thyroid
dysfunction during
Elderly hyperthyroid patients gested by a diffuse goiter; a thyroid recombinant

often have milder, more subtle, bruit; eye signs, such as proptosis, interleukin-2 therapy
in advanced malig-
and less typical symptoms that chemosis, periorbital edema, ex- nancies. Acta En-
docrinol (Copenh).
are often dominated by fatigue, traocular muscle dysfunction, or 1993;129:31-8. [PMID:

depression, weight loss, and optic neuropathy (inflammatory 8351956]

8. Miller KK, Daniels GH.
atrial fibrillation (11, 12). orbitopathy); pretibial myxedema Association between
or other, less common, dermato- lithium use and thy-
The term apathetic hyperthy- rotoxicosis caused by
pathies; soft tissue enlargement silent thyroiditis. Clin
roidism describes this clinical Endocrinol (Oxf ).
and clubbing of the fingers (thyroid
presentation. 2001;55:501-8.
acropachy); vitiligo; or premature [PMID: 11678833]
9. Stanbury JB, Ermans
Some elements of the history hair graying. The diagnosis of a AE, Bourdoux P, et al.

may also suggest a specific cause toxic multinodular goiter or a toxic Iodine-induced
hyperthyroidism: oc-
of the hyperthyroidism. Eye adenoma is supported by the find- currence and epi-
demiology. Thyroid.
pain or swelling, double vision, ing of multiple thyroid nodules or a 1998;8:83-100.

or a skin disorder on the shins single thyroid nodule on thyroid [PMID: 9492158]
10. U.S. Preventive Serv-
suggests Graves disease. Recent palpation. Fever and marked thy- ices Task Force.

pregnancy raises the possibility roid tenderness are findings that Screening for thyroid
disease: recommen-
point to subacute thyroiditis. dation statement.
of postpartum thyroiditis. Ante- Ann Intern Med.
Table 1 lists the frequencies of 2004;140:125-7.
rior neck pain, malaise, fever, and
many physical examination findings [PMID: 14734336]
sore throat are characteristic of 11. Trivalle C, Doucet
in hyperthyroid patients. J, Chassagne P, et al.
subacute thyroiditis. Amiodarone, Differences in the
signs and symptoms
lithium, alpha-interferon, What laboratory tests should of hyperthyroidism
interleukin-2, or potassium iodide clinicians use to diagnose in older and
younger patients.
use before or recent exposure to hyperthyroidism? J Am Geriatr Soc.
1996;44:50-3.
iodinated radiocontrast agents Serum TSH measurement is [PMID: 8537590]
increases the likelihood of drug- the best test to diagnose hyper- 12. Martin FI, Deam DR.
Hyperthyroidism in
induced or iodine-induced hyper- thyroidism. Levels will be low in elderly hospitalised
patients. Clinical fea-
thyroidism. Table 1 lists the both overt and subclinical hyper- tures and treatment
frequency of several hyperthyroid thyroidism. If the TSH level is outcomes. Med J
Aust. 1996;164:200-3.
symptoms. low, the clinician should order a [PMID: 8604186]

3 July 2012 Annals of Internal Medicine In the Clinic ITC1-3 © 2012 American College of Physicians
 Table 1. Frequency of Elements from the History and Physical Examination in Hyperthyroidism*
Variable Category Element Frequency, %
Clinical hyperthyroidism History Nervousness 99
Increased sweating 91
Heat intolerance 89
Palpitations 89
Fatigue 88
Weight loss 85
Tachycardia 82
Dyspnea 75
Weakness 70
Leg swelling 65
Eye signs 54
Hyperdefecation 33
Weight gain 5–10
Menstrual irregularity 22
Emotional lability 30–60
Physical examination Tachycardia 100
Goiter 100
Skin changes 97
Tremor 97
Bruit 77
Eye signs 30–45
Atrial fibrillation 10
Splenomegaly 10
Gynecomastia 10
Subclinical thyroiditis History Neck pain 91
Radiation to ears 64
Sore throat 36
Malaise 84
Recent upper respiratory illness 18
Anorexia 18
Myalgia 12
Nervousness 46
Perspiration 46
Physical examination Thyroid firm in consistency 100
Bilateral thyroid enlargement 45
Appearing acutely ill 50
Fever 57
Eye 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 clubbing
Vitiligo and premature Suggestive of organ-specific autoimmunity
hair graying

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

© 2012 American College of Physicians ITC1-4 In the Clinic Annals of Internal Medicine 3 July 2012
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 some
patients have normal T4 levels
with elevated T3 levels (i.e.,
T3 toxicosis).
Once the diagnosis of hyperthy-
roidism is confirmed, further test-
ing may be necessary to determine
the cause. When the symptoms
and physical signs strongly point
to Graves disease, it is reasonable
to forgo further diagnostic testing.
If the cause is not clear, the clini-
cian should order additional tests
because treatment differs consid-
erably for different causes. The
radioiodine uptake (RAIU) is the
most useful additional diagnostic
test and should be ordered
whenever the presentation is not
diagnostic of Graves disease.
Hyperthyroidism associated with
high 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 of
Hyperthyroidism Through Use
of Radioiodine Uptake) shows
the various causes of hyperthy-
roidism and how they can be
Differential Diagnosis of the Cause
of Hyperthyroidism Through Use of
Radioiodine Uptake
High or Normal
Graves disease
Toxic multinodular goiter
Toxic adenoma
Human chorionic gonadotropin–induced
hyperthyroidism
Thyroid stimulating hormone–producing
pituitary tumor
Low
Silent thyroiditis
Postpartum thyroiditis
Subacute (granulomatous) thyroiditis
Iodine-induced hyperthyroidism
Amiodarone-induced hyperthyroidism
Iatrogenic hyperthyroidism
Metastatic follicular thyroid cancer
Struma ovarii
3 July 2012 Annals of Internal Medicine
categorized according to the
RAIU.
A thyroid scan, which can be
done at the same time as the
RAIU, helps to distinguish
among these 3 high RAIU disor-
ders and should be done, espe-
cially in the presence of thyroid
nodularity (3). Graves disease
shows diffuse isotope uptake, toxic
multinodular goiter shows patchy
uptake, and a toxic adenoma
shows uptake only in a single
nodule. Other tests may be
considered when radioisotope
studies are contraindicated—for
example, because of pregnancy
or breast-feeding (13–16) or pa-
tient preference—and include
tests of serum for TSH-receptor
antibodies (TRAb), thyroid-
stimulating immunoglobulins
(TSI), thyroid-peroxidase anti-
bodies (TPO), thyroglobulin, and
human chorionic gonadotropin;
erythrocyte sedimentation rate;
imaging the thyroid with color
Doppler ultrasonography; and a
whole-body radioiodine scan.
Table 2 lists tests that are useful
in the diagnosis and differential
diagnosis of hyperthyroidism. 13. Dydek GJ, Blue PW.
Human breast
milk excretion of
What alternative explanations iodine-131 following
diagnostic and ther-
should clinicians consider in apeutic administra-
tion to a lactating
patients with possible patient with Graves’
hyperthyroidism? disease. J Nucl Med.
1988;29:407-10.
Conditions with clinical features [PMID: 3346746]
that can resemble those of hyper- 14. Morita S, Umezaki N,
Ishibashi M, Kawa-
thyroidism include infection, sepsis, mura S, Inada C,
Hayabuchi N. Deter-
anxiety, depression, the chronic fa- mining the breast-
tigue syndrome, atrial fibrillation of feeding interruption
schedule after ad-
other causes, and pheochromocy- ministration of
123I-iodide. Ann
toma. Thyroid hormone testing will Nucl Med. 1998;12:
usually distinguish most of these 303-6. [PMID:
9839494]
disorders from hyperthyroidism. 15. Gorman CA. Ra-
dioiodine and preg-
However, other conditions can be nancy. Thyroid.
a greater challenge because serum 1999;9:721-6.
[PMID: 10447020]
TSH levels are often low in these 16. Abalovich M, Amino
N, Barbour LA, et al.
conditions, which include preg- Management of thy-
nancy; hyperemesis gravidarum; roid dysfunction
during pregnancy
the euthyroid sick syndrome (the and postpartum: an
Endocrine Society
nonthyroidal illness syndrome); clinical practice
central hypothyroidism; and the guideline. J Clin En-
docrinol Metab.
use of some medications, most 2007;92:s1-7.
In the Clinic ITC1-5 © 2012 American College of Physicians
 Table 2. Laboratory and Other Studies for Hyperthyroidism
Test 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.

notably glucocorticoids, dopamine, normal but the T4 or T3 is above

and heparin (17). the reference range. Consultation
may also be helpful when the
When should clinicians cause is unclear; this is most
consult an endocrinologist often true when RAIU is low or
for diagnosing possible undetectable, whereas the diagno-
hyperthyroidism? sis is usually relatively straight-
The clinician should consider con- forward when RAIU is elevated.
sulting an endocrinologist when the Consultation should also be
presence of hyperthyroidism is un- strongly considered when the
certain, such as when the serum provider is uncertain or suspicious
TSH level is low but the T4 and T3 about the risk for or the presence
are within the population reference of thyroid storm or Graves
range, or when the TSH level is orbitopathy.
17. Spencer C, Eigen A,
Shen D, Duda M,
Qualls S, Weiss S, et
al. Specificity of sen-
sitive assays of thy-
rotropin (TSH) used Diagnosis... The clinician should make the diagnosis of hyperthyroidism from
to screen for thyroid the history, physical examination, and characteristic laboratory findings of a low
disease in hospital-
ized patients. Clin
serum TSH level associated with elevated serum levels for free T4 , FT4 I, total T3 ,
Chem. 1987;33:1391- or free T3 . The clinician should identify the cause of hyperthyroidism from clini-
6. [PMID: 3301067] cal features along with the RAIU and thyroid scan. In selected situations, the
18. Manji N, Carr-Smith
JD, Boelaert K, et al. additional tests described in Table 2 (TRAb, TSI, TPO antibodies, thyroglobulin,
Influences of age, erythrocyte sedimentation rate, human chorionic gonadotropin, color Doppler
gender, smoking,
and family history ultrasonography, and whole-body scanning) may facilitate determining the
on autoimmune thy- cause.
roid disease pheno-
type. J Clin
Endocrinol Metab.
2006;91:4873-80. CLINICAL BOTTOM LINE
[PMID: 16968788]

© 2012 American College of Physicians ITC1-6 In the Clinic Annals of Internal Medicine 3 July 2012

What nondrug therapies should
clinicians recommend?
Until thyroid disease is adequately
controlled, patients with hyperthy-
roidism should avoid heavy physical
exertion; reduce or eliminate caffeine
intake (to avoid aggravating the
symptoms); avoid over-the-counter
decongestants and cold remedies; dis-
continue smoking (smoking promotes
ophthalmopathy and disease recur-
rence) (18, 19); and avoid exogenous
sources of iodine, such as kelp, iodine
supplements, inorganic iodide, and
iodinated contrast agents (may ex-
acerbate the hyperthyroidism).
Table 3. Medications for Outpatient Treatment of Hyperthyroidism
First-Line Therapy
Beta-adrenergic blockade
Propranolol
Atenolol
Metoprolol
Nadolol
Antithyroid medications
Methimazole
Propylthiouracil
Radioactive iodine
Ancillary Therapy
Potassium iodine (SSKI)
Lithium
Cholestyramine
Nonsteroidal anti-inflammatory
drugs
Glucocorticoids
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.
3 July 2012 Annals of Internal Medicine
Treatment
How should clinicians choose and
prescribe drug therapy?
Table 3 describes the medications
available for the treatment of hy-
perthyroidism. Beta-adrenergic
blockade is appropriate for sympto-
matic patients with hyperthy-
roidism of any cause (3). Clinicians
have successfully used many differ-
ent beta-adrenergic blockers to
treat this condition.
Methimazole and propylthiouracil
(PTU) are the 2 antithyroid med-
ications that are available in the
Unites States (20). These agents
Dose Side Effects
10–40 mg QID CHF, asthma exacerbation
25–100 mg QD–BID CHF, asthma exacerbation
25–100 mg BID–QID CHF, asthma exacerbation
40–160 mg QD CHF, asthma exacerbation
5–120 mg QD Cutaneous reactions; increased
ALP; agranulocytosis 0.2%–0.4%
(dose-related)
50–300 mg TID–QID Cutaneous reactions; increased
AST/ALT; liver failure; agranulo-
cytosis 0.2%–0.4% (not dose-
related); ANCA-positive
vasculitis
10–30 mCi Causes hypothyroidism in
3–6 months; may acutely
exacerbate hyperthyroidism;
contraindicated with severe
ophthalmopathy; contraindicated
in pregnancy and nursing
Dose Notes
5 drops QID Acutely reduces thyroid
hormone release; use before
thyroidectomy for Graves
disease; do not use before
radioactive iodine therapy
300 mg QID Reduces thyroid hormone
release
1–2 g BID Binds thyroid hormone in the 19. Eckstein A, Quad-
intestines beck B, Mueller G, et
al. Impact of smok-
Variable doseing according Use to treat subacute thyroiditis ing on the response
to specific agent chosen to treatment of thy-
roid associated oph-
Prednnisone 20–40 mg daily Use to treat severe subacute thalmopathy. Br J
for 2–4 wk thyroiditis Ophthalmol.
2003;87:773-6.
[PMID: 12770979]
20. Cooper DS. Antithy-
roid drugs. N Engl J
Med. 2005;352:905-
17. [PMID: 15745981]
In the Clinic ITC1-7 © 2012 American College of Physicians
 inhibit thyroid hormone synthesis medications, beta-adrenergic
and lower thyroid hormone levels blockers, or glucocorticoid therapy
21. Nakamura H, Noh JY, in patients with Graves disease, (30). One exception is amiodarone-
Itoh K, et al. Compar-
ison of methimazole
toxic multinodular goiter, and toxic induced hyperthyroidism, which
and propylthiouracil adenoma (20). Both agents are may respond to antithyroid
in patients with hy-
perthyroidism generally quite effective (21), but medications (4, 5).
caused by Graves’ methimazole should be used be-
disease. J Clin En-
docrinol Metab. cause of the potential for hepatic Minor drug side effects with methi-
2007;92:2157-62.
failure with PTU (3). The optimal mazole and PTU include rash and
[PMID: 17389704]
22. Abraham P, Avenell duration of methimazole therapy is abnormal results on liver tests,
A, Watson WA, Park
CM, Bevan JS. An- usually 12–18 months, after which cholestatic changes with methima-
tithyroid drug regi-
it is tapered or discontinued if the zole (alkaline phosphatase), and he-
men for treating
Graves’ hyperthy- patient is asymptomatic and the patocellular enzyme elevations with
roidism. Cochrane
Database Syst Rev. TSH level is normal (3, 22). When PTU (aspartate transaminase, ala-
2005:CD003420. Graves disease recurs after discon- nine transaminase). Because PTU
[PMID: 15846664]
23. Benker G, Reinwein tinuation of antithyroid medica- can cause severe hepatocellular dam-
D, Kahaly G, et al. Is
tion, which it does in about 50% age with liver failure (31, 32), in
there a methimazole
dose effect on re- of cases (20, 23–25), clinicians usu- 2009 the U.S. Food and Drug Ad-
mission rate in
Graves’ disease? Re- ally recommend treatment with ministration issued an alert advising
sults from a long-
adrenergic blockers, radioactive clinicians to use methimazole in-
term prospective
study. The European iodine (I-131), or surgery. How- stead of PTU, except in thyroid
Multicentre Trial storm, cases of methimazole allergy,
Group of the Treat- ever, methimazole can be restarted
ment of Hyperthy-
and maintained at low doses for and in pregnant women in the first
roidism with
Antithyroid Drugs. more prolonged periods in patients trimester (3, 32). When given to
Clin Endocrinol
(Oxf ). 1998;49:451-7. who prefer this choice (3). women in early pregnancy, methi-
[PMID: 9876342] mazole has been reported to be asso-
24. Rittmaster RS, Ab-
bott EC, Douglas R, Antithyroid medications also effec- ciated with absence of a portion of
et al. Effect of methi- tively lower thyroid hormone levels scalp skin at birth (aplasia cutis) and
mazole, with or
without L-thyroxine, in patients with toxic multinodular a congenital blockage at the back of
on remission rates in
Graves’ disease. J
goiter or a toxic adenoma, but the nasal passage by abnormal bone
Clin Endocrinol medical therapy does not result in or soft tissue (choanal atresia).
Metab.1998;83:814-8.
[PMID: 9506733] permanent remission. Therefore, Agranulocytosis is a potentially life-
25. Maugendre D, Gatel
A, Campion L, et al.
treatment with I-131 or thyroidec- threatening disorder that occurs with
Antithyroid drugs tomy is the preferred primary treat- both drugs in about 0.2%–0.4% of
and Graves’ dis-
ease–prospective ment choice for these disorders. patients (33, 34), most often within
randomized assess-
ment of long-term
Nonetheless, long-term, low-dose the first few months of treatment; it
treatment. Clin En- methimazole therapy is reasonable occurs more commonly in patients
docrinol (Oxf ].
1999;50:127-32. for patients who choose this option receiving high doses (>40 mg/d)
[PMID: 10341866]
26. McDermott MT,
and agree to frequent monitoring of methimazole (35, 33, 36) but is
Kidd GS, Dodson LE (3). When patients are treated with not dose-related in patients taking
Jr, Hofeldt FD.
Radioiodine-induced I-131 or thyroidectomy, antithyroid PTU (35). PTU also causes more
thyroid storm. Case medications are often prescribed to antineutrophil cytoplasmic antibody–
report and literature
review. Am J Med. control the hyperthyroidism before positive vasculitis (37, 38).
1983;75:353-9.
[PMID: 6349350]
treatment and to reduce the risk for
27. Cooper DS. Antithy- thyroid storm after treatment (3, When should clinicians consider
roid drugs in the I-131 as primary therapy for
management of 26–29). Drugs used for this pur-
patients with
pose should be discontinued 7 days hyperthyroidism?
Graves’ disease: an
evidence-based before I-131 treatment to prevent Because of its effectiveness and
approach to thera-
peutic controversies. them from reducing the effective- overall safety, I-131 is 1 of the 3 pri-
J Clin Endocrinol ness of the treatment. mary treatment options for Graves
Metab. 2003;88:
3474-81. [PMID: disease (3, 39). It is also a good
12915620] Antithyroid medications should not choice for this disorder in patients
28. Burch HB, Wartofsky L.
Life-threatening thy- be used in patients with low RAIU who do not have remission with an-
rotoxicosis. Thyroid
storm. Endocrinol
hyperthyroidism because it tends to tithyroid medications (3). It achieves
Metab Clin North be self-limited and often responds remission in approximately 90% of
Am. 1993;22:263-77.
[PMID: 8325286] to nonsteroidal anti-inflammatory patients with Graves disease.

© 2012 American College of Physicians ITC1-8 In the Clinic Annals of Internal Medicine 3 July 2012
Hypothyroidism is the main levels that exceed the upper
side effect and occurs in virtually limit of the reference range more
all patients for whom treatment is than 2-fold with beta-adrenergic
effective. Most patients become blockade (3), methimazole (3), 29. Langley RW, Burch
HB. Perioperative
hypothyroid within 3–6 months or both for up to a month before management of the
thyrotoxic patient.
of I-131 therapy. Sialadenitis is I-131 therapy. However, methi- Endocrinol Metab
an occasional side effect from mazole should be discontinued Clin North Am.
2003;32:519-34.
uptake by the salivary glands. 7 days before I-131 treatment [PMID: 12800544]
30. Fatourechi V,
Worsening of preexisting Graves because otherwise it can Aniszewski JP, Fa-
orbitopathy is now a well- reduce the effectiveness of tourechi GZ, Atkin-
son EJ, Jacobsen SJ.
recognized potential complication this therapy. Clinical features and
of I-131 treatment (19, 40–43). outcome of suba-
cute thyroiditis in an
Patients with mild orbitopathy Pregnancy is an absolute contra- incidence cohort:
can receive I-131 but may benefit indication to I-131 treatment (15, Olmsted County,
Minnesota, study.
from pretreatment with glucocor- 16), and women of childbearing J Clin Endocrinol
Metab. 2003;88:
ticoids. Patients with moderate potential should have a negative 2100-5. [PMID:
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31. Williams KV, Nayak S,
choose another option (3). Treat- treatment. This therapy is not effec- Becker D, Reyes J,
Burmeister LA. Fifty
ment does not seem to increase tive in low RAIU hyperthyroidism years of experience
cancer mortality. Although there and should not be used (47). with propylthiouracil-
associated hepato-
was a small increase in thyroid toxicity: what have

cancer in I-131-treated patients, When should clinicians consider we learned?

J Clin Endocrinol
this may be related to intrinsic thyroidectomy as primary therapy? Metab. 1997;82:
1727-33. [PMID:
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most patients with Graves primary therapy for patients with 32. Cooper DS, Rivkees
SA. Putting propylth-
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within 3–6 months of I-131 in refractory cases of amiodarone- tive. J Clin

Endocrinol Metab.
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promptly recognized and treated for hyperthyroid patients who have Benker G, Lederbo-
gen S, Olbricht T,
before the onset of severe thyroid nodules and are suspected Reinwein D. Antithy-
roid drug-induced
hypothyroidism. to have cancer and in patients who agranulocytosis: clin-
cannot tolerate or who refuse alter- ical experience with
ten patients treated
For toxic multinodular goiters and native forms of therapy. Because at one institution
and review of the lit-
toxic adenomas, I-131 is consid- I-131 is contraindicated during erature. J Endocrinol
ered 1 of 2 preferred options for pregnancy, surgery may also be Invest. 1994;17:29-
36. [PMID: 7516356]
primary therapy (3). Hypothy- considered in pregnant women in 34. Sheng WH, Hung
CC, Chen YC, et al.
roidism is the main side effect of the second trimester whose hyper- Antithyroid-drug-
I-131 therapy in these 2 condi- thyroidism is not controlled with induced agranulocy-
tosis complicated by
tions but still is only present in antithypertensive medications. Sur- life-threatening in-
fections. QJM.
50%–75% of patients, in contrast gery may also be appropriate for 1999;92:455-61.
to nearly 100% of patients with patients who do not achieve remis- [PMID: 10627862]
35. Cooper DS, Gold-
Graves disease. sion with antithyroid medications, minz D, Levin AA, et
al. Agranulocytosis
particularly those with moderate associated with an-
Thyroid hormone levels often to severe Graves orbitopathy (3). tithyroid drugs. Ef-
increase transiently in the first fects of patient age
and drug dose. Ann
1–2 weeks after I-131 administra- Clinicians should use methimazole Intern Med.
1983;98:26-9.
tion, regardless of diagnosis. This to induce euthyroidism before sur- [PMID: 6687345]
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Fukata S, et al.
symptoms and has even been re- disease, but not those with toxic Methimazole-
ported to precipitate thyroid multinodular goiters or toxic ade- induced agranulocy-
tosis in patients with
storm in severely hyperthyroid nomas, should also receive oral Graves’ disease is
more frequent with
individuals (26, 27). Experts rec- potassium iodide during the week an initial dose of
ommend that clinicians pretreat before surgery (3) to further reduce 30 mg daily than
with 15 mg daily.
very symptomatic patients or thyroid hormone levels and to re- Thyroid. 2009;
19:559-63. [PMID:
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3 July 2012 Annals of Internal Medicine In the Clinic ITC1-9 © 2012 American College of Physicians
 gland. Outcomes are best when a and test results are within the refer-
37. Noh JY, Asari T, high-volume thyroid surgeon ence range, the clinician should
Hamada N, Makino F,
Ishikawa N, Abe Y, et does the procedure (3, 48). Most discontinue the beta-adrenergic
al. Frequency of ap-
pearance of
patients will be rendered hypothy- blocker, reduce the dose of antithy-
myeloperoxidase- roid by this treatment, depending roid medication, and continue clini-
antineutrophil cyto-
plasmic antibody on the extent of surgery, and should cal and laboratory assessments every
(MPO-ANCA) in be started on replacement doses of 3–6 months. If the serum TSH is
Graves’ disease pa-
tients treated with levothyroxine (1.7 µg/kg per d) be- normal after 12–18 months on re-
propylthiouracil and
the relationship be-
fore discharge from the hospital duced doses of antithyroid medica-
tween MPO-ANCA (3). Thyroidectomy is not indicated tion, the clinician can taper or stop
and clinical manifes-
tations. Clin En- for low RAIU hyperthyroidism the medication to determine
docrinol (Oxf ).
2001;54:651-4.
(47) other than for occasional pa- whether the patient has achieved
[PMID: 11380496] tients with refractory amiodarone- remission (3, 22). Some experts rec-
38. Chen YX, Yu HJ,
Ni LY, et al. induced hyperthyroidism. ommend measuring TRAb at this
Propylthiouracil-
associated antineu-
time, because a normal level indi-
trophil cytoplasmic How should clinicians monitor cates a greater likelihood of remis-
autoantibody- patients who are being treated for sion and predicts which patients can
positive vasculitis:
retrospective study hyperthyroidism? be successfully weaned from the an-
of 19 cases. J
Rheumatol. 2007;
Clinicians should do a baseline tithyroid medication (3, 46). If re-
34:2451-6. [PMID: complete blood count (CBC) with mission has not occurred, the clini-
17985400]
39. Abraham-Nordling M, a differential white blood cell (WBC) cian should consider treatment with
Wallin G, Lundell G, count and a liver panel, regardless of
Torring O. Thyroid I-131 or surgery, but a more pro-
hormone state and which treatment is chosen but par- longed course of low-dose methi-
quality of life at
long-term follow-up ticularly before initiating antithyroid mazole is reasonable if the patient
after randomized
treatment of Graves’
medications (3). Baseline studies are prefers this approach (3).
disease. Eur J En- important because hyperthyroidism
docrinol. 2007;
156:173-9. [PMID: itself and the various treatments can Patients who receive radioactive
17287406] all cause abnormalities. The moni- iodine should have a repeated clin-
40. Bartalena L, Mar-
cocci C, Bogazzi F, toring strategy after treatment ical assessment and laboratory
et al. Relation be-
tween therapy for
should differ depending on which testing 1–2 months after I-131
hyperthyroidism and treatment is chosen. After successful administration (3). Because
the course of Graves’
ophthalmopathy. treatment of any type, however, once serum TSH levels may remain
N Engl J Med.
1998;338:73-8.
patients are euthyroid (with or suppressed for as long as 6 weeks
[PMID: 9420337] without levothyroxine-replacement after chronically elevated T4 and T3
41. Tallstedt L, Lundell G,
Tørring O, et al. Oc- therapy) they should be assessed levels decrease to or below the nor-
currence of ophthal-
mopathy after treat-
clinically and have serum TSH mal range (47), it is important to
ment for Graves’ measured (with or without measure- measure both TSH and free T4
hyperthyroidism.
The Thyroid Study ment of free T4 ) every 6–12 months levels in the first 1–3 months after
Group. N Engl J Med.
1992;326:1733-8.
for the remainder of their lives. therapy; during this time, hypothy-
[PMID: 1489388] roidism can be characterized by
42. Träisk F, Tallstedt L, When antithyroid medications are either elevated TSH or low free T4
Abraham-Nordling M,
et al; Thyroid Study the treatment choice, patients should levels. Accordingly, thyroid hor-
Group of TT 96. Thy-
roid-associated
be advised to discontinue the med- mone–replacement therapy should
ophthalmopathy af- ications and notify their provider if be started when either the free T4
ter treatment for
Graves’ hyperthy- they develop signs or symptoms of level becomes low or the serum TSH
roidism with antithy-
roid drugs or
agranulocytosis (fever, sore throat), level becomes elevated. Serum
iodine-131. J Clin En- liver injury (jaundice, dark urine, TSH testing is recommended
docrinol Metab.
2009;94:3700-7. acolic stools, pruritus, abdominal 6–8 weeks after thyroid
[PMID: 19723755]
43. Acharya SH, Avenell A,
pain, nausea, vomiting), or vasculitis hormone–replacement therapy is
Philip S, Burr J, Bevan (fatigue, arthralgias) (3). The clini- started, with dose adjustment at
JS, Abraham P. Ra-
dioiodine therapy cian should order a repeated CBC 6- to 8-week intervals until the
(RAI) for Graves’ dis- with a differential WBC if patients TSH level is in the desired range.
ease (GD) and the
effect on ophthal- report fever or pharyngitis and a
mopathy: a system-
atic review. Clin En-
liver profile if they report symptoms After thyroidectomy for hyperthy-
docrinol (Oxf ). of liver injury (3). Once symptoms roidism, clinicians should start full
2008;69:943-50.
[PMID: 18429949] of hyperthyroidism have resolved replacement doses of levothyroxine

© 2012 American College of Physicians ITC1-10 In the Clinic Annals of Internal Medicine 3 July 2012
(1.7 µg/kg daily) (3) at or before then deciding whether to continue
hospital discharge. Serum TSH based on whether symptoms im-
should be tested 6–8 weeks later, prove as the TSH level becomes
with the dose adjusted at 6- to normal.
8-week intervals until the level is in
the desired range. How does a clinician recognize
and treat thyroid storm? 44. Ron E, Doody MM,
Becker DV, Brill AB, et
What is subclinical hyper- Thyroid storm, which some people al. Cancer mortality
thyroidism, and what are the call “thyroid crisis,” is a life-threatening following treatment
for adult hyperthy-
indications for treatment? condition characterized by exagger- roidism. Cooperative
Subclinical hyperthyroidism is low ated manifestations of thyrotoxico- Thyrotoxicosis
Therapy Follow-up
serum TSH levels combined with sis. It usually occurs in patients Study Group. JAMA.
1998;280:347-55.
T4 and T3 levels within the serum who have unrecognized or inade- [PMID: 9686552]
reference ranges (48, 49). Many pa- quately treated thyrotoxicosis 45. Sosa JA, Bowman
HM, Tielsch JM,
tients are asymptomatic, or hyper- combined with a precipitating Powe NR, Gordon
TA, Udelsman R. The
thyroidism symptoms, if present, event, such as thyroid or other importance of sur-
are usually mild. The RAIU is typi- surgery, infection, or trauma. Also, geon experience for
clinical and econom-
cally within the reference range, radioiodine therapy for severe ic outcomes from
thyroidectomy. Ann
and thyroid scan findings are con- hyperthyroidism may occasionally Surg. 1998;228:320-
sistent with the underlying cause precipitate thyroid storm. Fever 30. [PMID: 9742915]
46. Feldt-Rasmussen U,
(diffuse uptake for Graves disease, >102° F is the cardinal manifesta- Schleusener H,
patchy uptake for toxic multinodu- Carayon P. Meta-
tion of this condition. Tachycardia analysis evaluation
lar goiter, and isolated uptake for is usually present, and tachypnea is of the impact of thy-
rotropin receptor an-
toxic adenoma). common. Cardiac arrhythmias, tibodies on long
term remission after
congestive heart failure, and is- medical therapy of
Although there is agreement about chemic heart symptoms develop Graves’ disease.
the definition of subclinical hyper- frequently. Nausea, vomiting, diar-
J Clin Endocrinol
Metab. 1994;78:98-
thyroidism, there is substantially rhea, and abdominal pain are also 102. [PMID: 8288723]
47. Uy HL, Reasner CA,
less agreement about how and even common features. Central nervous Samuels MH. Pattern
whether to treat it (48, 49). Experts system manifestations include hy-
of recovery of the
hypothalamic-
disagree because most patients have perkinesis, psychosis, and coma (28). pituitary-thyroid axis
only a few mild symptoms, and following radioactive
iodine therapy in pa-
TSH levels often return to normal Serum total and free T4 and total tients with Graves’
disease. Am J Med.
without treatment. They agree that and free T3 levels are usually elevated, 1995;99:173-9.
patients with TSH levels <0.1 mU/L and the serum TSH level is unde- [PMID: 7625422]
48. Surks MI, Ortiz E,
or those who are convincingly tectable. Other common laboratory Daniels GH, et al.
Subclinical thyroid
symptomatic should be treated abnormalities include anemia, disease: scientific re-
(48, 49). Debate on management leukocytosis, hyperglycemia, azote- view and guidelines
for diagnosis and
of patients with levels ≥0.1 mU/L mia, hypercalcemia, and elevated management. JAMA.
2004;291:228-38.
but that are still lower than the liver enzymes. [PMID: 14722150]
reference range continues (48, 49), 49. Gharib H, Tuttle RM,
Baskin HJ, Fish LH,
although recent studies have raised Under most circumstances, the Singer PA, McDer-
concern about potential negative clinician must diagnose thyroid mott MT. Subclinical
thyroid dysfunction:
effects of hyperthyroidism on the storm on the basis of suspicious a joint statement on
management from
heart (50, 51), bones (52, 53), and but nonspecific clinical findings. the American Asso-
central nervous system. For exam- Serum thyroid hormone levels ciation of Clinical En-
docrinologists, the
ple, data now indicate an increased are elevated in this disorder, but American Thyroid
Association, and the
risk for atrial fibrillation when the waiting for test results will delay Endocrine Society.
TSH level is < 0.3 mU/L (50). therapy that could be lifesaving J Clin Endocrinol
Metab. 2005;90:581-
When patients with subclinical hy- if thyroid storm is present. 5; discussion 586-7.
[PMID: 15643019]
perthyroidism have symptoms that Furthermore, thyroid hormone 50. Sawin CT, Geller A,
may be caused by hyperthyroidism levels do not reliably distinguish Wolf PA, et al. Low
serum thyrotropin
but are too vague for the clinician patients with thyroid storm from concentrations as a
risk factor for atrial
to be confident about their cause, those with uncomplicated thyro- fibrillation in older
some experts recommend starting toxicosis. Therefore, clinical fea- persons. N Engl J
Med. 1994;331:1249-
an antithyroid medication and tures are the key to this diagnosis, 52. [PMID: 7935681

3 July 2012 Annals of Internal Medicine In the Clinic ITC1-11 © 2012 American College of Physicians
 and a scoring system is available
to help clinicians determine
when to make the diagnosis (28)
(Table 4).
The immediate goals of therapy are
to decrease thyroid hormone syn-
thesis with methimazole or PTU;
inhibit thyroid hormone release
with sodium or potassium iodide;
reduce the heart rate with a beta-
blocker, such as esmolol, metopro-
lol, or propranolol or a calcium
channel blocker, such as diltiazem;
support the circulation with gluco-
corticoids, IV fluids, oxygen, and
cooling; and treat the precipitating
condition (28). The Box (Treat-
ment of Thyroid Storm) provides
more detailed information about
therapy.
When should patients be
hospitalized?
Hyperthyroid patients should be
hospitalized when thyroid storm is
present, impending, or suspected.
When thyroid storm was first de-
scribed, the acute mortality rate
was nearly 100%. Although the
prognosis today is much better
with aggressive therapy, mortality
remains around 20%.

Table 4. Thyroid Storm Scoring System*

Feature Score
Fever, ° F
99–99.9 5
100–100.9 10
101-101.9 15
102-102.9 20
103-103.9 25
>104 30
Central nervous system agitation
Absent 0
Mild 10
51. Gammage MD, Parle Moderate 20
JV, Holder RL,
Roberts LM, Hobbs Severe 30
FD, Wilson S, et al. Cardiac–pulse, bpm
Association between
serum free thyroxine 99–109 5
concentration and
atrial fibrillation. 110–119 10
Arch Intern Med. 120–129 15
2007;167:928-34.
[PMID: 17502534] 130–139 20
52. Foldes J, Tarjan G, ≥140 25
Szathmari M, Varga F,
Krasznai I, Horvath C. Atrial fibrillation 10
Bone mineral densi-
ty in patients with Cardiac–CHF
endogenous sub- Absent 0
clinical hyperthy-
roidism: is this Mild (edema) 5
thyroid status a risk Moderate (rales) 10
factor for osteoporo-
sis? Clin Endocrinol Severe (pulmonary edema) 15
(Oxf ). 1993;39:521-7.
[PMID: 8252739] Gastrointestinal signs
53. Bauer DC, Ettinger B, Absent 0
Nevitt MC, Stone KL;
Study of Osteo- N, V, D, Pain 10
porotic Fractures Re- Jaundice 20
search Group. Risk
for fracture in Precipitant history
women with low
serum levels of Absent 0
thyroid-stimulating Present 10
hormone. Ann In-
tern Med. 2001;
134:561-8. [PMID: *Thyroid storm score <25 = unlikely; 25–44 = suggestive; >45 = likely.
12803168]

© 2012 American College of Physicians ITC1-12 In the Clinic Annals of Internal Medicine 3 July 2012
 Treatment of Thyroid Storm
1. 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 h
4. Support circulation
• Glucocorticoids in stress doses
• Fluids, oxygen, cooling
5. Treat precipitating cause

When should clinicians consider present, impending, or suspected.

consulting an endocrinologist or
ophthalmologist?
Clinicians should consider consult-
ing an endocrinologist after
diagnosis for help developing an
optimal management plan; when
unexpected events occur; when
there are treatment complications;
when significant Graves eye disease
is present; if the patient is preg-
nant; and when thyroid storm is
Some published guidelines suggest
co-management with an endocri-
nologist in all cases of hyperthy-
roidism (1). Clinicians should
consider consulting an ophthalmol-
ogist when the patient has double
vision; impaired visual acuity,
visual fields, or color vision; signifi-
cant eye discomfort; proptosis
>22 mm; or extraocular muscle
dysfunction.

Treatment... Hyperthyroidism associated with high or normal RAIU usually re-

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

CLINICAL BOTTOM LINE

What measures do stakeholders
use to evaluate the quality of
care for patients with
hyperthyroidism?
Federal legislation passed in 2006
required the Centers for Medicare
& Medicaid Services (CMS) to
create a physician reporting system
for quality measures regarding cov-
ered services furnished to Medicare
Practice
beneficiaries. CMS named this
Improvement
program the Physician Quality Re-
porting Initiative (PQRI). Eligible
professionals who meet the criteria
for satisfactory submission of data
for services can earn incentive
payments. The 2012 PQRI consists
of 318 quality measures; however,
none specifically apply to persons
with hyperthyroidism.

3 July 2012 Annals of Internal Medicine In the Clinic ITC1-13 © 2012 American College of Physicians
 What do professional Clinical Endocrinologists have re-
organizations recommend cently published evidence-based
regarding care of patients with guidelines for management of
hyperthyroidism? hyperthyroid patients (3). These
The American Thyroid Association guidelines are incorporated into
and American Association of this report.

In the Clinic

In the Clinic
PIER Module
http://pier.acponline.org/physicians/diseases/d175/

Tool Kit
d175.html
PIER module on hyperthyroidism from the
American College of Physicians. PIER modules
provide evidence-based, updated information on
current diagnosis and treatment in an electronic
format designed for rapid access at the point of
care.
Hyperthyroidism
Patient Information
www.annals.org/site/patientinformation/
patientinformation.xhtml
Patient information that appears on the following
pages for duplication and distribution to
patients.
www.nlm.nih.gov/medlineplus/thyroiddiseases.html
Information on thyroid-associated diseases, from
the National Institutes of Health’s
MedlinePLUS.
www.hormone.org/Resources/thyroid-disorders.cfm
www.hormone.org/Spanish/index.cfm
Patient resources on thyroid disorders, including
information in both English and Spanish, from
the Hormone Foundation.
www.uptodate.com/contents/patient-information
-hyperthyroidism-overactive-thyroid-beyond-the-basics
Information for patients on hyperthyroidism, from
UpToDate.

Clinical Guidelines
www.aace.com/sites/default/files/
HyperGuidelines2011.pdf
Practice guidelines for the evaluation and treatment
of hyperthyroidism and hypothyroidism, from the
American Association of Clinical
Endocrinologists in May 2011.
www.annals.org/content/140/2/125.full
www.annals.org/content/140/2/128.full
U.S. Preventive Services Task Force
recommendation statement on screening for
thyroid disease, and a summary of the evidence,
published in Annals of Internal Medicine in
January 2004.
http://jcem.endojournals.org/content/92/8_suppl/s1.full
Practice guidelines on the management of thyroid
dysfunction during pregnancy and the
postpartum period, from the Endocrine Society
in August 2007.

Diagnostic Tests and Criteria

http://pier.acponline.org/physicians/diseases/d175/
tables/d175-tlab.html
Table listing laboratory and other studies for
thyrotoxicosis.

© 2012 American College of Physicians ITC1-14 In the Clinic Annals of Internal Medicine 3 July 2012
THINGS YOU SHOULD In the Clinic
Annals of Internal Medicine
KNOW ABOUT
HYPERTHYROIDISM

What is hyperthyroidism?
• A disorder that occurs when the thyroid, a butterfly-
shaped gland located in the neck, makes excess
thyroid hormones.
• Thyroid hormones regulate how your body uses and
stores energy.
• Having too much of these hormones can speed up every
function 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 of
20 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). • Your doctor may order a radioactive iodine
uptake test to identify what is causing your
What are common symptoms? hyperthyroidism.
• Feeling too hot, increased sweating. • A thyroid scan may be ordered to check the shape
and size of your thyroid gland, and to see if any
• Muscle weakness, trembling hands. nodules are present.

• 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 your
hormone levels.
• Hyperthyroidism is diagnosed when blood tests show
that certain hormones levels are abnormal.
Patient Information
How is it treated?
• Treatment depends on the cause of the
hyperthyroidism; your age, physical condition, and
preferences; and the severity of the condition.
• Medications may be used to reduce the amount of
hormone your thyroid gland makes.
• Beta-blockers can help control your symptoms,
including rapid heart rate, tremors, anxiety, and heat
intolerance.
• Radiation to destroy the thyroid with radiation,
called radioiodine ablation, provides a permanent
treatment.
• The thyroid may be removed surgically.

For More Information

www.thyroid.org/patients/patient_brochures/hyperthyroidism.html
www.thyroid.org/patients/faqs/hyperthyroidism.html
Information 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 Kidney
Diseases.
CME Questions
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, before
which she felt “completely healthy.”
Medical history is otherwise unremarkable,
and she takes no medications.
Physical examination shows a thin, restless
woman with smooth, fine, moist skin and
fine hair. Blood pressure is 108/60 mm Hg,
pulse rate is 96/min, respiration rate is
14/min, and BMI is 18.1. Mild lid lag is
noted, but no proptosis, diplopia, or
conjunctival injection is detected. Her
thyroid gland is soft and enlarged
approximately 2-fold. There is a mild, fine
tremor of the outstretched hands. Reflexes
are 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 most
appropriate next test for this patient?
A. MRI of the pituitary gland
B. Thyroid anti–peroxidase antibody test
C. Thyroid radioactive iodine uptake
determination
D. Thyroid scan
E. Thyroid-stimulating immunoglobulin
measurement
2. A 35-year-old woman is evaluated for
diaphoresis, a 3.6-kg (8.0-lb) weight loss,
and elevated blood glucose levels 6 weeks
after delivering her second child. She has an
18-year history of type 1 diabetes mellitus,
which has been successfully treated with an
insulin pump for the past 8 years. Her
glycemic control during this period has been
outstanding, with an average hemoglobin
A1c value of 6.2%. Although her diabetes
was well-controlled during most of the
recent pregnancy, the insulin dosage needed
to be increased by almost 50% to maintain
glycemic control. Postpartum, the patient
reduced the insulin dosage to her
prepregnancy baseline requirements, but
this step has been inadequate to control
her blood glucose level.
On physical examination, vital signs are
normal. Tachycardia, tremor, hyperreflexia,
and a wide pulse pressure are noted.
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Results of a complete blood count and
metabolic panel are normal.
Measurement of which of the following
is most likely to diagnose the cause of
the deteriorating glucose control?
A. Antitransglutaminase antibody titers
B. Hemoglobin A1c value
C. Postprandial glucose level
D. Thyroid-stimulating hormone level
E. Urine free cortisol level
3. An 18-year-old woman is evaluated for
tachycardia, nervousness, decreased
exercise tolerance, and weight loss of
6 months’ duration. She has otherwise
been healthy. Her sister has Graves
disease. She takes no medications.
On physical examination, blood pressure
is 128/78 mm Hg, pulse rate is 124/min,
respiration rate is 16/min, and BMI is
19.5. There is no proptosis. An
examination of the neck reveals a
smooth thyroid gland more than
1.5 times the normal size. Cardiac
examination reveals regular tachycardia
with a grade 2/6 early systolic murmur at
the base. Her lungs are clear to
auscultation. Laboratory results reveal
the following: human chorionic
gonadotropin, 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 most
appropriate treatment regimen at this
time?
A. Atenolol only
B. Methimazole only
C. Atenolol and methimazole
D. Radioactive iodine and methimazole
4. A 55-year-old man is evaluated for a
4-month history of weight loss, heat
intolerance, tremor, and hyperdefecation
and a 1-week history of dry eyes that are
sensitive to light and frequently injected.
He reports no blurred or double vision
but does relate having been previously
diagnosed with a “thyroid condition” and
having a severe allergic reaction to
methimazole therapy. The patient
currently takes no medications.
ITC1-16 In the Clinic
On physical examination, blood pressure
is 140/88 mm Hg, pulse rate is 120/min,
respiration rate is 18/min, and BMI is 22.
Pupils are equal, round, and reactive to
light and accommodation; extraocular
movements are intact. Mild bilateral
conjunctival injection and periorbital
edema are noted. There is no chemosis,
but some slight lid lag and proptosis are
present. Examination of the neck reveals
a smooth thyroid gland that is 3 times its
normal size. Cardiac examination shows
tachycardia and a regular rhythm. There
is 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 most
appropriate treatment for this patient?
A. Immediate thyroidectomy
B. Orbital decompression surgery
C. Prednisone and radioactive iodine
ablation
D. Radioactive iodine ablation alone
5. A 76-year-old woman is reevaluated
after abnormal results on thyroid
function tests performed 2 weeks ago.
The patient feels well. She has a history
of hypertension, atrial fibrillation,
gastroesophageal reflux disease, and
depression. Current medications are
metoprolol, amiodarone, warfarin,
omeprazole, and sertraline.
On physical examination, blood pressure is
125/65 mm Hg, pulse rate is 83/min, and
respiration rate is 15/min. The thyroid
gland is smooth and of normal size.
Cardiac examination reveals an irregularly
irregular rhythm. Deep tendon reflexes are
normal. 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 is
most likely responsible for the laboratory
results?
A. Amiodarone
B. Metoprolol
C. Omeprazole
D. Sertraline
Annals of Internal Medicine 3 July 2012