Treatment of Hyper- and
Committees from AACE and ATA are currently working on updating
the hyper- and hypothyroidism treatment guidelines.
REVIEWED BY JEFFREY R. GARBER, MD; BY CONNI BERGMANN KOURY, EDITOR-IN-CHIEF
iagnosing thyroid disease can be challenging.
TABLE 1. FEATURES OF HYPERTHYROIDISM
According to the American Association of
Clinical Endocrinologists (AACE), the sensitive • Nervousness and irritability
thyroid-stimulating hormone (TSH or thyro- • Palpitations and tachycardia
tropin) assay has become the single best screening tool • Heat intolerance or increased sweating
for hyper- and hypothyroidism. Additionally, serum TSH • Tremor
is the most sensitive test for detecting mild thyroid hor- • Weight loss or gain
mone excess or deficiency.1 • Alterations in appetite
Committees from AACE and the American Thyroid • Frequent bowel movements or diarrhea
Association (ATA) are currently working on updated • Dependent lower-extremity edema
guidelines for the diagnosis and treatment of both hyper- • Sudden paralysis
and hypothyroidism. Jeffrey R. Garber, MD, Associate • Exertional intolerance and dyspnea
Professor of Medicine at Harvard Medical School and • Menstrual disturbance (decreased flow)
Chief of Endocrinology at Harvard Vanguard Medical • Impaired fertility
Associates, spoke to Review of Endocrinology and provided • Mental disturbances
a preview of what will be addressed by the new guidelines. • Sleep disturbances (including insomnia)
• Changes in vision, photophobia, eye irritation, diplopia, or
Hyper- and hypothyroidism are highly prevalent condi- • Fatigue and muscle weakness
tions that usually come to the attention of the primary • Thyroid enlargement (depending on cause)
care physician first.2 Hyperthyroidism develops when the • Pretibial myxedema (in patients with Graves’ disease)
body produces too much thyroxine.3 This disorder occurs
in almost 1% of Americans and affects women five to ten mon in women and usually begins after age 20 years.
times more often than men. In its mildest form hyperthy- Hypothyroidism—underactivity of the thyroid gland—
roidism may not cause recognizable symptoms, other- occurs when the thyroid gland produces less than the
wise the symptoms can be discomforting, disabling, or normal amount of thyroid hormone. The result is the
even life-threatening. The condition can significantly slowing down of many bodily functions, and although it
accelerate the body’s metabolism, causing sudden weight may be temporary, it is usually a permanent condition.
loss, a rapid or irregular heartbeat, sweating, and nerv- Estimates of Americans with thyroid dysfunction vary
ousness or irritability. from 10 to 12 million to as high as 25 to 30 million. Most
Several treatment options exist for patients with have hypothyroidism. The overwhelming majority of
hyperthyroidism, such as antithyroid medications and cases are due to chronic immune (Hashimoto’s) thy-
radioactive iodine to slow the production of thyroid hor- roiditis, radioactive iodine therapy, or surgery.
mones. Treatment can include surgery. Graves’ disease,
the most common cause of hyperthyroidism, occurs HYPERTHRYOIDI SM
when the immune system mistakenly attacks the thyroid Causes of hyperthyroidism include:
gland and causes it to overproduce thyroxine. Graves’ • Graves’ disease (toxic diffuse goiter)
disease is rarely life-threatening, and can develop at any • toxic adenoma
age in either men or women. It is, however, more com- • Plummer’s disease (toxic multinodular goiter)
20 I REVIEW OF ENDOCRINOLOGY I APRIL 2009
TABLE 2. DIAGNOSIS OF HYPERTHYROIDISM TABLE 4. FEATURES OF HYPOTHYROIDISM
• Weight and blood pressure • Fatigue
• Pulse rate and cardiac rhythm • Weight gain from fluid retention
• Thyroid palpation and auscultation (to determine thyroid • Dry skin and cold intolerance
size, nodularity, and vascularity) • Yellow skin
• Neuromuscular examination • Coarseness or loss of hair
• Eye examination (to detect evidence of exophthalmos or • Hoarseness
ophthalmopathy) • Goiter
• Dermatologic examination • Reflex delay, relaxation phase
• Cardiovascular examination • Ataxia
TABLE 3. LABORATORY EVALUATION: • Memory and mental impairment
HYPERTHYROIDISM • Decreased concentration
• TSH level • Irregular or heavy menses and infertility
• T4 and assessment of serum T4 • Myalgias
• Triiodothyronine (T3) radioimmunoassay (RIA) or assess- • Hyperlipidemia
ment of serum free T3 • Bradycardia and hypothermia
• Thyroid autoantibodies, including TSH receptor antibodies • Myxedema fluid infiltration of tissues
or thyroid-stimulating immunoglobulins
• Radioactive iodine uptake (3) The optimal choice for antithyroid drugs and the
• Thyroid scan—with either 123I (preferably) or 99mTc optimal monitoring of patients on antithyroid drugs.
pertechnetate “We are also going to address about some of the issues
surrounding propylthiouracil and its potential for toxici-
• painful subacute thyroiditis ty,” he said.
• silent thyroiditis (4) What types of surgery should be performed and
• iodine-induced hyperthyroidism what patients should receive which procedures.
• excessive pituitary TSH or trophoblastic disease (5) Who should perform thyroid surgery.
• excessive ingestion of thyroid hormone (6) The use of radioiodine.
The signs of hyperthyroidism are attributable to the (7) The role of long-term antithyroid therapy.
effects of excess thyroid hormone, and the severity of the (8) Special considerations will be discussed, such as
symptoms can vary (Table 1). To diagnose the condition surgery for thyroid disease in pediatric patients and the
(Table 2), a comprehensive history should be performed treatment of those with Graves’ ophthalmopathy, and
and a laboratory evaluation must be made (Table 3). the role of TSH receptor antibodies in certain cases.
Although the diagnosis of overt Graves’ disease with oph-
thalmopathy is obvious, it may be more difficult in elderly HYPOTHYROIDI SM
patients. In the United States, the most common form of pri-
mary hypothyroidism is chronic autoimmune thyroiditis
SCREENING AND TRE ATMENT (Hashimoto’s disease). Other causes include surgical
F OR HYPERTHYROIDI SM removal of the thyroid gland, thyroid gland ablation with
New guidance emerging from the upcoming AACE/ radioactive iodine, external irradiation, a biosynthetic
ATA clinical guidelines regarding hyperthyroidism will defect in iodine organification, lymphoma, and drugs
address: such as lithium or interferon. Central causes can include
(1) Subclinical hyperthyroidism: who, when, and how? pituitary and hypothalamic disease.
“The approach to elderly patients, postmenopausal Symptoms of hypothyroidism typically relate to the
women, and those with heart disease or osteoporosis duration and severity of the condition (Table 4). Usually
will differ from the approach to healthy, younger any physician can make the diagnosis of hypothyroidism,
patients,” Dr. Garber said. however, a clinical endocrinologist may be needed in cer-
(2) Stratification of patients with subclinical hyperthy- tain situations (Table 5). To diagnose the condition, an
roidism, meaning those with very low TSH as opposed appropriate laboratory evaluation of TSH level is critical
to those who are just below the normal limit. (Table 6).
APRIL 2009 I REVIEW OF ENDOCRINOLOGY I 21
TABLE 5. SPECIAL SITUATIONS: TABLE 6. LABORATORY EVALUATION:
• Patients aged ≤18 years • TSH
• Patients unresponsive to therapy • Assessment of free T4 estimate
• Pregnant patients • Thyroid autoantibodies—antithyroid peroxidase and
• Cardiac patients antithyroglobulin autoantibodies
• Presence of goiter, nodule, or other structural changes in • Thyroid scan, ultrasonography, or both (if necessary to
the thyroid gland evaluate suspicious structural thyroid abnormalities)
• Presence of other endocrine disease
if you do not believe in screening, which patients, such
SCREENING AND TRE ATMENT as those with certain comorbid conditions, should be
F OR HYPOTHYROIDI SM evaluated for aggressive case findings that indicate evalu-
According to Dr. Garber, the new AACE/ATA hypothy- ation and potential treatment,” Dr. Garber said.
roid guidelines will include more than 30 recommenda- The new guidelines will look at the role of desiccated
tions. Specific areas that the guidelines will address are thyroid hormone and T3 and T4 combinations, and spe-
thyroid antibodies—including TSH receptor antibodies: cial concerns in pregnancy for either of these. More ques-
Under what circumstances and in which patients should tions to be addressed include:
these measurements be used? The guidelines will also dis- • How should older people with hypothyroidism be
cuss the role of clinical scoring systems in the evaluation treated?
of patients with hypothyroidism, the role of diagnostic • How should people with adrenal insufficiency be
tests apart from serum TSH and serum thyroid hormone treated?
levels in patients with hypothyroidism (for example, cho- • How is hypothyroidism best managed during preg-
lesterol and muscle enzymes), and the preferred thyroid nancy?
hormone measurements that should be made in addition “Physicians who are not necessarily endocrinologists but
to TSH in patients with hypothyroidism. are familiar with the diagnosis and treatment of hypothy-
Other questions to answered by the new guidelines roidism should be able to take care of most patients with
include: primary hypothyroidism,” Dr. Garber said. “Some, however,
• Should different tests be used in pregnant patients? fall into separate categories and should be seen by endo-
• When should thyroid testing be performed in hospi- crinologists, for example pregnant women.” The experts
talized patients? will also make recommendations regarding which patients
• When should TSH levels be measured in patients should not be treated with thyroid hormone; the use of
being treated for hypothyroidism? thyroid hormone in treating obesity and depression; and
A controversial area to be covered in the upcoming the roles of iodine supplementation and selenium, an
guidelines is defining the upper normal of TSH. For exam- emerging area of research.
ple, Dr. Garber said, should patients with a TSH between The AACE/ATA guidelines will highlight the complexity
2.5 µIU/L and the upper limit of normal for a given lab test of thyroid disease. It is important to note, said Dr. Garber,
be considered for treatment with thyroid hormone? How that “subclinical disease often remains undiagnosed, but
can we identify these patients, and which of these patients through sound judgment, timely intervention, and patient
who have TSH levels above the given laboratory reference involvement, an optimal level of care is attainable.” ■
should be considered for treatment?
“A very interesting area of discussion that will be cov- Jeffrey R. Garber, MD, is Associate Professor of Medicine
ered in the guidelines,” Dr Garber said, “is when should at Harvard Medical School and Chief of Endocrinology at
patients with normal thyroid levels be considered for Harvard Vanguard MedicalAssociates. He may be reached
treatment?” Specifically this speaks to euthyroid women at firstname.lastname@example.org.
who are pregnant or planning to get pregnant, and who
1. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Prac-
have a history of positive thyroid peroxidase antibodies. tice for the Evaluation and Treatment of Hyperthyroidism and Hypothyroidism. Endocr
“Can miscarriages and premature delivery be reduced by Pract. 2002;8:458–469.
2. Singer PA, Cooper DS, Levy EG, et al. Treatment guidelines for patients with hyper-
treating these women with thyroid hormone?” thryoidism and hypothyroidism. JAMA. 1995;273:808–812.
The upcoming AACE/ATA guidelines will address the 3. Hyperthyroidism. The Mayo Clinc. www.mayoclinic.com/health/hyperthyroidism/
DS00344. Accessed March 5, 2009.
patient populations that should be evaluated for hypo- 4. Hypothyroidism. The Mayo Clinic.
thyroidism and if screening has a role in this disease. “Or, www.mayoclinic.com/health/hypothyroidism/DS00353. Accessed March 5, 2009.
22 I REVIEW OF ENDOCRINOLOGY I APRIL 2009