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CASE STUDY
Initial Presentation
CME jointly sponsored by
Wayne State University School of Medicine A 25-year-old woman presents to her physician
and JCOM
with symptoms of fatigue, headaches, and fluctuat-
ing weight. On examination, vital signs are within normal
This article has a companion CME exam that follows
range. Body mass index (BMI) is 28 kg/m2. Thyroid examina-
the article. To earn credit, read the article and com-
tion is unremarkable. A thyroid-stimulating hormone (TSH)
plete the CME evaluation on pages 306 and 307.
Estimated time to complete this activity is 1 hour. level is ordered and found to be low at 0.1 mIU/L (reference
Faculty disclosure information appears on page 304. range, 0.5–5.0 mIU/L). Free levorotatory thyroxine (T4) and
Release date: 15 June 2008; valid for credit through free triiodothyronine (T3) levels are subsequently checked
30 June 2009. and found to be normal.
Program Audience
Primary care physicians.
• How should the results of the patient’s thyroid function
Educational Needs Addressed tests be interpreted?
Signs and symptoms of hyperthyroidism are wide-
ranging and the frequency and severity of symp-
toms can vary, which makes diagnosis a chal- A patient with low TSH and normal T4 and T3 is consid-
lenge. Primary care physicians are often the first ered to have subclinical hyperthyroidism. Typically, these
to evaluate these patients. A detailed evaluation patients do not have clear signs and symptoms of hyper-
that includes questions about extent and duration thyroidism. The prevalence of subclinical hyperthyroidism
of symptoms, past medical history, family history, ranges from 0.7% to 12.4%. This variability is partly due to
physical examination (including thyroid examina- differences among studies in the definition of a low serum
tion), and appropriate laboratory tests can help
TSH value [1–4].
guide the treating physician to the etiology. Proper
The causes of subclinical hyperthyroidism are similar to
management depends on properly identifying the
cause of hyperthyroidism. Regular monitoring for those of overt hyperthyroidism (Table 1). The most common
changes in thyroid function is required, as progno- causes of subclinical hyperthyroidism are
sis can be adversely affected if a euthyroid state • Exogenous administration of levothyroxine for treating
is not maintained.
hypothyroidism. Among patients taking levothyroxine,
Educational Objectives as many as 25% may have low serum TSH values [5]
After participating in this CME activity, primary care • Autonomously functioning thyroid adenomas and
physicians should be able to multinodular goiters
1. Differentiate between etiologies of hyperthy-
roidism • Subacute thyroiditis
2. Describe management options for subclinical
hyperthyroidism • Less commonly, Graves’ disease
3. Outline the typical course of and management
strategies for subacute thyroiditis
4. Understand the approach to diagnosis and
management of Graves’ disease
5. Describe signs and symptoms of thyroid storm From the Department of Medicine, Section of Endocrinology, Diabetes and
Metabolism, Temple University School of Medicine, Philadelphia, PA.
Table 2. Clues to Causes of Hyperthyroidism A variant of subacute thyroiditis, sometimes called sub-
acute granulomatous thyroiditis, is characterized by neck
Feature Likely Disorder
pain and a tender, diffuse goiter in addition to the other
Diffuse goiter Graves’ disease characteristics. Postpartum thyroiditis is subacute thyroid-
Exophthalmos Graves’ disease itis that occurs in women within 1 year after parturition.
Pain and tenderness on the thyroid area Subacute thyroiditis The typical course of subacute thyroiditis is initially
Nodular goiter Toxic adenoma or characterized by hyperthyroidism followed by euthyroid-
toxic nodular goiter
ism, hypothyroidism, and ultimately restoration of normal
Recent intravenous contrast exposure Iodine-induced
thyroid function in most cases (Figure).
Patient taking amiodarone for a cardiac Amiodarone-induced
Subacute thyroiditis may have some pathologic simi-
condition
larities with Hashimoto’s disease, as many patients with
Hypothyroid patient taking levothyroxine Exogeneous
painless thyroiditis have high serum concentrations of an-
tithyroid microsomal (thyroid peroxidase) antibodies and
some develop overt chronic autoimmune thyroiditis several
As this patient is presenting in the immediate postpartum years later [14].
period, the physician should have a high degree of suspicion Treatment of patients with subacute thyroiditis is directed
for postpartum thyroiditis, whose presentation is similar to at relieving thyroid pain and tenderness and ameliorating
subacute thyroiditis. There are other clinical clues that can be symptoms of hyperthyroidism, if present. The few patients
helpful in identifying the cause of hyperthyroidism (Table 2). who have significant symptoms of hyperthyroidism, such
as palpitations, anxiety, or tremor, may benefit from treat-
ment with b blockers for few weeks. Some patients require
• Which tests may be helpful in the workup of the pa- no treatment because their symptoms are mild or subside by
tient with hyperthyroidism? the time they seek medical attention or when the diagnosis
is established. In some patients, anti-inflammatory therapy
with a nonsteroidal anti-inflammatory drug is indicated to
Laboratory tests may help in differentiating between the control pain; in patients with severe pain, steroids may be
causes of hyperthyroidism. Presence of TSH receptor anti- needed [16].
bodies, in particular thyroid-stimulating immunoglobulin,
indicates Graves’ disease. Very high thyroglobulin levels are Case Continued
consistent with subacute thyroiditis. The patient is prescribed b blockers for her post
The radioactive iodine uptake and scan can be helpful in partum thyroiditis. She does not return to the office
determining the etiology of hyperthyroidism and can help for follow-up.
in directing treatment. Radioactive iodine uptake measures The patient returns for evaluation 5 years later. She
how much of the radioactivity given orally has been taken up reports that 5 years ago her thyroid “had gotten back to
by the thyroid over a period of time and is typically reported normal” after a few months on b blockers, but she has now
as a percentage. The scan complements the uptake and developed similar symptoms consisting of palpitations,
shows how the activity is distributed in the thyroid. Table 3 heat intolerance, and weight loss. On examination, she has
shows the results of radioactive iodine uptake and scan in the a diffuse goiter estimated at 2 to 3 times the normal size,
most commonly seen causes of hyperthyroidism. lid lag, and exophthalmos. TSH is suppressed at less than
0.002 mIU/L, and her T4 and T3 levels are high. TSH receptor
antibody level is elevated.
• What is subacute thyroiditis?
600
500
400
300 40
200
100 20
TG, mg/mL
16 50 10
TSH, µU/mL
14 40 8
12 30 6
10 20 4
8 10 2 Normal
range
FTI
6 0 0
4
2
10 20 30 40 50 60 70 150
Figure. Course of subacute thyroiditis. FTI = free thyroxine index; TG = thyroglobulin; TSH = thyroid-stimulating hormone.
(Reprinted with permission from DeGroot LJ, Larsen PR, Hennemann G. Acute and subacute thyroiditis. In: The thyroid and its
diseases. 6th ed. New York: Churchill Livingstone; 1996:705.)
in combination with antithyroid drugs, they can rapidly However, there are patients in whom it may be reason-
ameliorate severe hyperthyroidism and can also be used to able to delay radioiodine (or surgery), and therefore anti-
prepare a hyperthyroid patient for early surgery. thyroid drugs are the treatment of choice. Included in this
group are patients with mild hyperthyroidism and patients
Other medications. A number of other medications have with small goiters or with goiters that shrink during thio
been used in the management of hyperthyroidism, includ- namide therapy. If radioiodine is chosen, the patient must be
ing the following: comfortable with the decision to ablate the thyroid, which in
most cases will result in permanent hypothyroidism.
• Glucocorticoids inhibit peripheral T4 to T3 conver-
Physicians and patients must also be aware that radioio-
sion and, in patients with Graves’ hyperthyroidism,
dine therapy may be associated with an increased risk of the
reduce thyroid hormone secretion. They have been
development or worsening of Graves’ ophthalmopathy [26].
used in patients with severe hyperthyroidism and
However, ophthalmopathy did not progress in a study of
thyroid storm
patients with minimal ophthalmopathy who were carefully
• Lithium blocks thyroid hormone release, but its use monitored to avoid hypothyroidism [27]. Some physicians
has been limited by its toxicity advocate the use of glucocorticoids at the time of radioiodine
• Cholestyramine, given in a dose of 4 g 4 times daily treatment to prevent such effects [28].
with methimazole, lowers serum T4 and T3 concen- Others suggest that radioactive iodine may not be the
trations more rapidly than methimazole alone treatment of choice in patients with significant ophthalmop-
athy. However, careful control of thyroid function before
Radioactive Iodine Ablation and after therapy and cessation of smoking by the patient
Ablation with radioiodine is widely used for the treatment may minimize ocular changes.
of Graves’ hyperthyroidism. It is the therapy of choice in the Radioactive iodine may be given as primary therapy to
United States, selected by approximately 70% of thyroid spe- patients with well-tolerated hyperthyroidism. In compari-
cialists [25]. It is considerably less popular in Europe (22%) son, patients who are not tolerating hyperthyroidism well,
and Japan (11%). are elderly, or have underlying heart disease are usually
Adapted with permission from Ross DS. Treatment of Graves’ hyperthyroidism. In: Rose BD, editor. UptoDate. Waltham (MA): UptoDate; 2008.
Copyright 2008, UptoDate, Inc. For more information, visit www.uptodate.com.
pretreated with an antithyroid drug to ameliorate hyperthy- in patients who have an obstructive goiter or a very large
roidism before radioactive iodine treatment. goiter, in pregnant women who are allergic to antithyroid
The goal of radioactive iodine therapy is destruction of drugs, and in patients who have allergies or poor compliance
the gland, with the early development of hypothyroidism. on antithyroid drugs but refuse radioactive iodine. Surgery
This eliminates the risk of recurrent hyperthyroidism. On the would also be indicated if there were a coexisting suspicious
other hand, some physicians prefer lower doses of radioactive or malignant thyroid nodule. However, most thyroid nodules
iodine with the aim of achieving a euthyroid state while low- associated with Graves’ disease are benign, in which case
ering the risk of early hypothyroidism [29]. However, many of surgery would not be recommended [31]. Patients who want
these patients have persistent subclinical or overt hyperthy- rapid restoration of euthyroidism, are concerned about radio-
roidism. Furthermore, there is a risk of both recurrent overt activity, or have had an adverse effect with thionamide drugs
hyperthyroidism and insidious-onset late hypothyroidism. may also prefer surgery.
Approximately 20% of patients fail the first radioactive Thyroidectomy during pregnancy may be necessary in
iodine treatment and require a subsequent dose. These pa- women who cannot tolerate antithyroid drugs because of
tients usually have more severe hyperthyroidism or larger allergy or agranulocytosis. The indications for surgery are
goiters. similar to those in nonpregnant women and men. Table 4
summarizes and compares treatment options for Graves’
Radioactive iodine therapy in toxic adenoma or toxic multi- hyperthyroidism.
nodular goiter. Depending upon patient preference, either ra-
dioactive iodine therapy or surgery is the treatment of choice Case Continued
for toxic adenoma or toxic multinodular goiter. An occasional The patient is started on methimazole, and her hy
patient can be managed, if preferred or necessary for other perthyroidism is well controlled with this treatment.
reasons, with antithyroid drugs. One year later she presents to the emergency department
Radioactive iodine therapy is less controversial in pa- with dyspnea, palpitations, fever, tremor, and agitation.
tients with a toxic adenoma or toxic multinodular goiter. Thyroid function tests show results consistent with severe
Areas of focal autonomy take up radioiodine well, while hyperthyroidism. She also has atrial fibrillation with rapid
uptake is limited in adjacent and contralateral thyroid tis- ventricular response. Upon questioning, the patient reports
sue that has been suppressed by the hyperthyroid state. As that she has not taken her thyroid medication for a while,
a result, radioiodine tends to destroy only the autonomous since she ran out.
areas, and most patients remain euthyroid after radioiodine
administration [30].
• What does the patient’s presentation suggest?
Surgery
With the availability of other options, surgery is a less popular
therapy for Graves’ hyperthyroidism. It is primarily indicated Patients with severe and life-threatening thyrotoxicosis
typically have an exaggeration of the usual symptoms of may not be her best long-term therapy option. Definitive
hyperthyroidism. This type of presentation is usually called therapy with radioactive iodine treatment may be a better
thyroid storm. choice for this patient.
Cardiovascular symptoms include severe tachycardia
along with congestive heart failure in many patients. Hyper Corresponding author: Elias S. Siraj, MD, Associate Professor of Medi-
pyrexia to 104ºF to 106ºF is common. Agitation, delirium, cine, Temple University Hospital, 3322 N. Broad St., Philadelphia, PA
psychosis, stupor, or coma are common and are considered 19140.
by many to be essential to the diagnosis. Severe nausea,
vomiting, or diarrhea, and hepatic failure with jaundice can Financial disclosures: None.
also occur.
Although thyroid storm can develop in patients with References
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precipitated by an acute event such as thyroid or nonthyroi- (thyroid-stimulating hormone) in older patients without hy-
perthyroidism. Arch Intern Med 1991;151:165–8.
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2. Parle JV, Franklyn JA, Cross KW, et al. Prevalence and follow-
advent of appropriate preoperative preparation of patients up of abnormal thyrotrophin (TSH) concentrations in the
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• How is thyroid storm managed?
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uncomplicated hyperthyroidism, except that the drugs are
the third National Health and Nutrition Examination Survey
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meta-analysis. Eur J Endocrinol 1994;130:350–6.
medications, each of which has a different mechanism of
8. Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin
action. b Blockers are used to control symptoms induced concentrations as a risk factor for atrial fibrillation in older
by increased adrenergic tone. A thionamide, such as meth persons. N Engl J Med 1994;331:1249–52.
imazole, is needed to block new hormone synthesis. An 9. Auer J, Scheibne P, Mische T, et al. Subclinical hyperthyroid-
iodinated radiocontrast agent can be used to inhibit the ism as a risk factor for atrial fibrillation. Am Heart J 2001;
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help block the release of thyroid hormones. Glucocorticoids 10. Cappola AR, Fried LP, Arnold AM, et al. Thyroid status, car-
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• What should be recommended for long-term manage- 12. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid
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Copyright 2008 by Turner White Communications Inc., Wayne, PA. All rights reserved.
DIRECTIONS: Each of the questions below is followed by several possible answers. Select the ONE lettered answer
that is BEST in each case and circle the corresponding letter on the answer sheet.
2. All of the following could be manifestations of subacute 5. In regard to thyroid storm, all of the following are true
thyroiditis EXCEPT EXCEPT
A. Hyperthyroidism A. Patients may present with congestive heart failure
B. Hypothyroidism B. Usually there is an identifiable precipitating factor
C. Pretibial myxedema C. Blocking the conversion of T4 to T3 is an important
D. Thyroid pain and tenderness part of the treatment
D. The incidence of surgically induced thyroid storm
3. All of the following regarding radioactive iodine therapy has increased recently
in Graves’ disease are true EXCEPT
A. It is the most widely used therapy in the United
States
B. It can lead to agranulocytosis
C. It may be associated with worsening ophthalmopa-
thy
D. It results in permanent hypothyroidism in most
patients
Participants may earn 1 credit by reading the article named above Please print clearly:
and correctly answering at least 70% of the accompanying test
questions. A certificate of credit and the correct answers will be Name:__________________________________________________
mailed within 6 weeks of receipt of this page to those who success-
MD/DO/Other:_________________________________________
fully complete the test.
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Circle your answer to the CME questions below:
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101 E. Alexandrine, Lower Level
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Detroit, MI 48201
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with the extent of their participation in the activity.
Release date: 15 June 2008
Expiration date: 30 June 2009