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Helfand M. Screening for Thyroid Disease [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2004 Jan. (Systematic Evidence Reviews, No. 23.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.


Search Strategy

We identified articles published before 1998 from the reference lists of previous reviews9, 12, 13, 23, 24, 76, 82–87 and by searching our own files of over 1,600 full-text articles from the period 1910 to 1998. We then searched MEDLINE® and EMBASE® from 1996 to February 2002, PREMEDLINE March 2002, and the Cochrane Library (2002, Issue 2) to identify additional articles. In a MEDLINE® search, the medical subject headings (MeSH) thyroid function tests and thyroid diseases were combined with the term mass screening, and the text words screening or case-finding. We conducted a separate search for controlled studies of the effect of thyroid-directed treatments on potential complications of subclinical thyroid disease, using the word levothyroxine in title, abstract, or keywords combined with terms for clinical trials. We also searched MEDLINE® from 1966-May 2002 for articles about the adverse effects of thyroid hormone replacement. Periodic hand searching of endocrinologic and major medical journals, review of the reference lists of retrieved articles, and suggestions from peer reviewers of earlier versions of this article supplemented the electronic searches.

Inclusion Criteria

We selected controlled trials of treatment of thyroid dysfunction that reported at least one health outcome (symptoms, cognitive function, or quality of life) or lipid levels. Broad inclusion criteria were used to get a picture of the benefits and adverse effects of treatment on patients with different degrees of thyroid dysfunction. Specifically, we included any trial that used TSH levels as a criterion for entry, in any population, including patients with known thyroid disease. We also identified observational studies of treatment for subclinical thyroid dysfunction; we included recent studies that had not been included in previous meta-analyses.13, 24, 25, 88

To assess the prevalence of thyroid disease and the causal relationships between thyroid dysfunction and potential complications, we used the following sources:

  • Previous meta-analyses and systematic reviews.
  • More recent cross-sectional, cohort, and case-control studies of the prevalence of overt or subclinical thyroid dysfunction.
  • Cross-sectional and longitudinal studies of the relationship between an elevated or low TSH to potential complications of subclinical hypothyroidism or subclinical hyperthyroidism.

For these categories of studies, we included studies in the general adult population, a demographic segment of the adult population, or among patients seen in the general clinic setting. We excluded studies of screening for congenital or familial thyroid disorders and studies of screening in inpatients, institutionalized patients, and series of patients seen in specialized referral clinics for depression or obesity.

Finally, we identified observational studies of the long-term adverse effects of levothyroxine therapy. We excluded studies of suppressive doses of thyroxine; to be included, the study had to include at least some patients that were taking replacement doses of thyroxine.

Data Extraction

We used predefined criteria from the USPSTF to assess the internal validity of trials, which we rated as “good,” “fair,” or “poor.” We also rated the applicability of each study to screening. The rating system is described in detail elsewhere.89 (The criteria are listed as column headings in Table 3.) We also abstracted information about its setting, patients, interventions, and outcomes. When possible, we recorded the difference between the probability of a response in the treatment and control groups for each complication studied.

Table 3. Quality of Randomized Trials of Thyroxine Replacement Therapy.


Table 3. Quality of Randomized Trials of Thyroxine Replacement Therapy.

Cover of Screening for Thyroid Disease
Screening for Thyroid Disease [Internet].
Systematic Evidence Reviews, No. 23.
Helfand M.


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