Patients with serum thyroid-stimulating hormone (TSH) levels outside
the reference range and levels of free thyroxine (FT4) and triiodothyronine
(T3) within the reference range are common in clinical practice.
The necessity for further evaluation, possible treatment, and the urgency
of treatment have not been clearly established.
To define subclinical thyroid disease, review its epidemiology, recommend
an appropriate evaluation, explore the risks and benefits of treatment and
consequences of nontreatment, and determine whether population-based screening
MEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality,
National Guideline Clearing House, the Cochrane Database of Systematic Reviews
and Controlled Trials Register, and several National Health Services (UK)
databases were searched for articles on subclinical thyroid disease published
between 1995 and 2002. Articles published before 1995 were recommended by
Study Selection and Data Extraction
A total of 195 English-language or translated papers were reviewed.
Editorials, individual case studies, studies enrolling fewer than 10 patients,
and nonsystematic reviews were excluded. Information related to authorship,
year of publication, number of subjects, study design, and results were extracted
and formed the basis for an evidence report, consisting of tables and summaries
of each subject area.
The strength of the evidence that untreated subclinical thyroid disease
is associated with clinical symptoms and adverse clinical outcomes was assessed
and recommendations for clinical practice developed. Data relating the progression
of subclinical to overt hypothyroidism were rated as good, but data relating
treatment to prevention of progression were inadequate to determine a treatment
benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations
in serum cholesterol were rated as fair but data relating to benefits of treatment
were rated as insufficient. All other associations of symptoms and benefit
of treatment were rated as insufficient or absent. Data relating a serum TSH
concentration lower than 0.1 mIU/L to the presence of atrial fibrillation
and progression to overt hyperthyroidism were rated as good, but no data supported
treatment to prevent these outcomes. Data relating restoration of the TSH
level to within the reference range with improvements in bone mineral density
were rated as fair. Data addressing all other associations of subclinical
hyperthyroid disease and adverse clinical outcomes or treatment benefits were
rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy
is a special case and aggressive case finding and treatment in pregnant women
can be justified.
Data supporting associations of subclinical thyroid disease with symptoms
or adverse clinical outcomes or benefits of treatment are few. The consequences
of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L)
are minimal and we recommend against routine treatment of patients with TSH
levels in these ranges. There is insufficient evidence to support population-based
screening. Aggressive case finding is appropriate in pregnant women, women
older than 60 years, and others at high risk for thyroid dysfunction.