Full Text Review
Please note: In 2003, the CTF updated its Grades of
Recommendations to include an "I Recommendation" for situations where
insufficient evidence exists to allow a recommendation to be made.
(Formerly, these situations were captured under a "C
Recommendation".) This change is not retroactive, and all
"C Recommendations" made prior to 2003 have not been
reevaluated in light of the new "I" recommendation grade. For a
discussion of these recommendation grades, please link to the 2003 article in
the Canadian Medical Association Journal here.
Screening for Thyroid Disorders and Thyroid Cancer in
Asymptomatic Adults
Prepared by Marie-Dominique Beaulieu, MD, MSc,
FCFP, Associate Professor of Family Medicine, University of Montreal, Quebec,
drawing from materials prepared for the U.S. Preventive Services Task Force
These recommendations were finalized by the Task Force in January 1994
Contents
Overview
As in 1990,<
1>
the Canadian Task Force on the Periodic Health Examination has concluded
that there is not enough evidence to recommend the inclusion of screening
for thyroid dysfunction (hyperthyroidism and hypothyroidism) in asymptomatic
adults. The effectiveness of screening for thyroid cancer has also been
poorly evaluated so that neither inclusion nor exclusion of screening for
thyroid cancer can be recommended in asymptomatic adults. The line between
truly asymptomatic and mildly symptomatic adults may, however, be difficult
to draw. Considering the high prevalence of thyroid disease, particularly
hypothyroidism in women, and the fact that some studies have shown that
affected women may benefit from early treatment, it is recommended that
clinicians maintain a high index of suspicion and not hesitate to use immunometric
thyroid stimulating hormone (TSH) assays to investigate individuals with
vague symptoms that could be related to thyroid dysfunction.
Burden
of Suffering
Hyperthyroidism
and Hypothyroidism
The definitions of what constitute "asymptomatic" hyperthyroidism
and hypothyroidism are far from clear. Overt hyperthyroidism and hypothyroidism
are defined as a triad of the classical signs and symptoms of thyroid dysfunction,
abnormal TSH levels, and abnormal thyroid function tests (TT4, FT4, etc).
Sub-clinical conditions are defined by the presence of abnormal TSH levels,
thyroid function test results in the upper or lower normal ranges, and
the absence of symptoms. However, the signs and symptoms of hypothyroidism
and hyperthyroidism are very vague in nature, insidious, and are often
attributed by patients to normal aging. They are not necessarily reported.<2>
The vague nature of the symptoms can be misleading; one study showed that
8% of patients with a diagnosis of depression were suffering from undetected
hypothyroidism.<3>
Community surveys have reported prevalence rates
of overt hyperthyroidism of less than 1.9%,
the rates being comparable in elderly populations.<4> If "sub-clinical"
cases are included, the prevalence rate can be as high as 2.7%.<4> In
a well conducted community study, the annual incidence rate of overt hyperthyroidism
was estimated to be 2 to 3 per 1,000
women.<4>
The prevalence of hypothyroidism is three times higher
among women than men. The prevalence in an unselected community population
of young, middle-aged and elderly individuals is about 1.4%
and the estimated annual incidence 1
to
2 per 1,000
women.<4> Surveys of geriatric populations have yielded estimated prevalence
rates for overt hypothyroidism of 0.2% to 3%.<5> The reported prevalence
of sub-clinical hypothyroidism ranges from 0.9% to 5.2% in the adult population<5>
and from 2.6% to 20% in the elderly population.<6>
Thyroid Cancer
Cancer of the thyroid represents 1.5%
of cancers in women and 0.5% of cancers in men. In 1990,
this cancer was responsible of the death of 113
Canadians, 41 males
and 72 females.<7> Cancer of the thyroid includes several cell types:
papillary and follicular carcinomas, which are rarely fatal with appropriate
treatment, and anaplastic carcinoma, which is one of the most lethal of
all cancers. Papillary cancer occurs more frequently in adults younger
than 50 years. Anaplastic carcinoma is the more common form of thyroid
cancer after the age of 60. An undisputed risk factor is neck radiation.
Maneuver
Hyperthyroidism
and Hypothyroidism
The measurement of circulating T4 levels used to diagnose
overt thyroid dysfunction is not useful for detecting mild or subclinical
conditions in adults. The measurement of basal TSH levels is the most sensitive
screening test. The new generation of sensitive immunoradiometric TSH assays
can reliably detect a concentration as low as 0.01
mU/L.
Normal values range between 0.3 mU/l and 5 mU/l, but some variations around
those values are possible in different laboratories. Clinical studies have
reported a sensitivity of 80% to 100%
and a specificity of nearly 100%
for the early detection of subclinical hyperthyroidism and hypothyroidism.<8>
Thyroid Cancer
The usual screening test for thyroid cancer is neck
palpation. Ultrasonography, scintigraphy and needle aspiration are reserved
for diagnostic evaluations. The accuracy of neck palpation varies with
the examiner’s skill and the size of the mass. Among patients referred
for the evaluation of a suspect solitary nodule, the sensitivity and specificity
of neck palpation was 63% and 62% compared to ultrasonography. In one study
of neck palpation in asymptomatic adults, the sensitivity was 15%
and the specificity 100%
compared with ultrasonography.<9> Therefore, a negative examination
does not exclude the possibility of having a thyroid cancer.
Effectiveness
of Screening and Treatment
Hyperthyroidism
and Hypothyroidism
The effectiveness of treatment of subclinical hyperthyroidism
has never been evaluated. Treatment of hyperthyroidism can be cumbersome
and expensive. The choice of a definitive treatment depends on many factors,
of which the patient’s age and severity of the clinical disease are the
most important. Clearly, the treatment strategy is not based solely on
laboratory tests. Hence, decisions about how to treat sub-clinical hyperthyroidism
rest on evaluation of the clinical impact of the laboratory abnormalities.
There has been no randomized trial (RCT) of the effectiveness
of a screening program for sub-clinical hypothyroidism in a completely
asymptomatic population. However, there have been two RCTs of the effectiveness
of early treatment of sub-clinical hypothyroidism, and there is some evidence
concerning the natural history of this condition.
The transition from sub-clinical to overt hypothyroidism
does not appear to be inevitable and is estimated to vary from 5% to 8%
annually. If both sub-clinical hypothyroidism and asymptomatic autoimmune
thyroiditis are present the rate increases to 12-20%
annually.<4>
Most experts now consider that an increase in TSH
levels above the normal range indicates an insufficiency of circulating
hormones.<10>
Levels above 10
mU/l are considered as definitely abnormal, and those between 5 mU/l and
10
mU/l are considered as being in the "grey area" in the absence of any symptoms
or signs of hypothyroidism.
Treatment of mild and sub-clinical hypothyroidism
with T4 replacement therapy has been found to return the TSH and T4 levels
to normal and to ameliorate some cardiac function indicators. Improvements
in other factors, such as resting heart rate, sodium secretion, serum lipid
levels and nerve conduction velocities, have not been found to be statistically
or clinically significant.
Two randomized controlled trials of the efficacy
of early treatment of sub-clinical hypothyroidism in women have shown that
some patients benefited from treatment as their level of well-being increased.<11,12>
In addition, treated patients had a statistically significant increase
in the systolic interval, an index of cardiac function. However, limitations
in the study designs warrant caution in generalizing the results to all
perimenopausal and postmenopausal women, especially to very old women,
since none of these studies included women above 75 years of age. One study,
by Cooper and associates,<11>
was conducted in a sample of women previously treated for hyperthyroidism.
Though an increase in TSH level revealed a real deficit in thyroid hormone,
the likelihood that these women would have developed overt hypothyroidism
in the future may have been greater than the usual asymptomatic population.
The second trial by Nystr ¨ om and collaborators<12>
randomly selected 22 of 78 women with confirmed sub-clinical hypothyroidism,
identified through a community survey. Treatment conferred a clinical benefit
to 25% of the cases. As there were no clinical indices to predict who would
respond to treatment, this suggests that three out of four women may have
been treated unnecessarily.
Latrogenic hyperthyroidism has been considered as
a potential danger of treatment of sub-clinical hypothyroidism. Iatrogenic
hyperthyroidism can precipitate angina or atrial fibrillation in susceptible
individuals, namely in the elderly with restricted cardiac reserve. However,
this iatrogenic condition can occur in any patient treated for hypothyroidism,
and can be avoided by proper monitoring.
Thyroid Cancer
The benefits of early detection of thyroid cancer are
not well defined. Five-year survival rates are better for patients with
earlier stages of cancer at diagnosis.<13>
There have been no controlled trials demonstrating that asymptomatic persons
detected by screening have better outcomes than those who sought care because
of symptoms. There is no basis on which to conclude that regular neck palpation
could have a major effect on the natural history of this infrequent cancer.
Recommendations
of Others
Few Canadian organisations have issued recommendations
on screening for thyroid diseases. The U.S. Preventive Services Task Force
does not recommend screening of asymptomatic adults.<14>
Conclusions
and Recommendations
Hyperthyroidism
and Hypothyroidism
There is still insufficient evidence to support the
inclusion of screening for hyperthyroidism and hypothyroidism among asymptomatic
adults (C Recommendation).
However, community surveys and clinical trials have clearly demonstrated
that an important proportion of individuals labelled as suffering from
subclinical disease in fact had some symptoms. The high prevalence of hypothyroidism
among perimenopausal and postmenopausal women warrants a high index of
clinical suspicion and liberal use of the sensitive TSH assay in the presence
of even vague and subtle complaints. RCTs have shown that such patients
can benefit from early treatment. Paradoxically, women over 75 years of
aged have been excluded from most studies of the effectiveness of early
treatment, but are still the target of screening for many physicians.
Thyroid Cancer
For thyroid cancer, there is no evidence to suggest
that regular neck palpation by a physician would have any impact on the
outcome of the disease but further evaluation is required (C
Recommendation).
Unanswered
Questions (Research Agenda)
A well planned randomized controlled trial should evaluate
the effectiveness of screening and early treatment of hypothyroidism in
apparently asymptomatic women. Such a trial would be most valuable if it
could determine effectiveness in very old women as well as in middle-aged
and perimenopausal women. The issue of the ideal screening interval should
also be clarified.
Evidence
A MEDLINE search between 1989
and 1993
was conducted using the key words: hyperthyroidism and hypothyroidism,
with the subheadings screening and prevention and control. Only original
articles were considered. The search yielded 12
new articles. Priority was given to the highest levels of evidence according
to the CTF methodology.
This review was initiated in December 1992
and recommendations were finalized by the Task Force in January 1994.
Full Citation
Link to Structured Abstract of
this review
Link to Summary Table of this
review
Link to Selected References list of this review
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