How Should We Manage Sub-Clinical Thyroid Disease?

Abstract & Commentary

Comment by Ralph R. Hall, MD, FACP, Emeritus Professor of Medicine University of Missouri-Kansas City School of Medicine; AACE member; Associate Editor, Internal Medicine Alert.

Synopsis: Treatment may be necessary but controversy still exists.

Sources: Gharib H, et al. Endocrine Practice. 2004;10: 497-501; Surks MI, et al. JAMA. 2004;281:228-238

These studies note that: ". . .sub-clinical thyroid dysfunction is a common clinical problem with many controversial issues regarding screening, evaluation, and management."

To develop an evidence-based approach to unresolved issues, the American Association of Clinical Endocrinology (AACE), the American Thyroid Association (ATA), and the Endocrine Society (TES), jointly sponsored a Consensus Development Conference which was held in September 2002.

The conference followed the principles of evidence-based medicine to make their recommendations. The published recommendations were not reviewed by members of the sponsoring organizations prior to their publication in 2004. After reviewing the recommendations and noting that there was still disagreement regarding some aspects of the recommendations, the leadership of the AACE, ATA, TES, appointed 2 members from each organization who practice clinical thyroidology to review these recommendations. Gharib and colleagues have now published the results of their review of the recommendations.

Treatment of Sub-Clinical Hypothyroidism

Sub-clinical hypothyroidism is defined as high levels of thyroid stimulation hormone (TSH) associated with normal levels of free thyroxin (free T4) and triiodothyronine (T3). The prevalence is 4-10% in the general population and up to 20% in women older than 60 years of age.

The original panel recommended against the treatment of patients with TSH levels between 4.5 and 10 mU/L; but that treatment was reasonable for patients with TSH levels > than 10 mU/L. The representatives from the reviewing organizations noted that evidence for not treating these patients was lacking and pointed out that thyroid failure was a continuum and, therefore, it might be reasonable to treat these patients.

Treatment of Sub-Clinical Hyperthyroidism

Sub-clinical hyperthyroidism is defined as low levels of TSH associated with normal levels of free T4 and free T3. It is more common in women, blacks, and the elderly. The treatment panel recommended observing patients with partial suppression of TSH (levels, 0.1-0.4 mU/L), but to treat patients with complete TSH suppression (levels < 0.1 mU/L). The reviewing organizations agreed with these recommendations, but stated that the strength of evidence was insufficient for these recommendations to be definitive.


It is impossible to abstract the thorough academic and clinical approaches used in these evaluations and recommendations. Physicians who care for these patients should read the reports and the article with examples of patient problems that accompanies the paper by Surks and associates.1

A recent study, not available when these guidelines were written, lends support to treating sub-clinical hypothyroidism.2 Serter et al studied 30 female pre-menopausal patients with TSH between 4 and 10 mU/L. Twenty-six healthy, euthyroid, subjects were used as controls. Pre-treatment total cholesterol (TC) and low-density cholesterol (LDL-C) were significantly higher in the sub-clinical hypothyroid group. Treatment targets for TSH were < than 2 mU/L. TC, LDL-C, and the TC/high-density cholesterol (HDL-C) ratio were significantly improved after 6 months of thyroid replacement therapy. Mean changes were -21 mg/dL for the TC and -30.3 mg/dL for the LDL-C and the TC/HDL-C ratio improved from 4.8 to 4.1. The changes are significant enough to substantiality improve the cardiovascular risk profile.

The argument against treating these patients was based on a study that found that 20% of the patients treated for hypothyroidism are treated with too large a dose of thyroxin with resulting TSH levels in the hyperthyroid range. Overtreating patients increases their risk of bone mineral loss and the potential for increased risk of cardiac arrhythmias.

Surks3 has pointed out that the original panels’ review "repeatedly states that the panels’ recommendations were for populations and that physicians should use their best clinical judgment for management of individual patients."

The management of sub-clinical hypothyroidism is an instance where a therapeutic trial, for 6 months to 1 year, might be useful. Based on objective findings at 6 months to 1 year, a decision could be made to continue or stop the therapy.


1. Surks MI, et al. JAMA. 2004;291:292-297.

2. Serter R. J Endocrinol Invest. 2004;27: 897-903.

3. Surks MI. Endocrine Practice. 2004;10:513.