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.
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
Beaulieu MD. Screening for thyroid disorders
and thyroid cancer in asymptomatic adults. In: Canadian Task Force on the
Periodic Health Examination.
Canadian
Guide to Clinical Preventive Health Care. Ottawa: Health Canada,
1994; 612-18.