Subclinical Hypothyroidism: To Treat or Not to Treat?

Abstract & Commentary

By Ralph R. Hall, MD, FACP, FACSM, Emeritus Professor of Medicine University of Missouri-Kansas City School of Medicine. Dr. Hall is a consultant for Aventis.

Synopsis: Treating subclinical hypothyroidism decreased arterial stiffness.

Source: Owen PJD, et al. Subclinical hypothyroidism, arterial stiffness, and myocardial reserve. J Clin Endocrinol Metab. 2006;91:2126-2132.

The cardiovascular system is one of the principal targets of thyroid hormone. Subclinical hypothyroidism (SCH), ie, the detection in the serum of elevated thyroid stimulating hormone (TSH) levels in the presence of free T4 and T3 levels within the normal range, is usually discovered on biochemical testing and associated with no definitive clinical signs or symptoms.

SCH in some, but not all, studies has been associated with an increased risk of cardiovascular disease but its impact on arterial function is less clear. Therefore, the objective of this study was the assessment of arterial and cardiac function.

This was a 6-month controlled observational study using pulse wave analysis and tissue Doppler dobutamine stress echocardiography. Nineteen female SCH patients with raised TSH, normal free T4, and no cardiovascular disease (mean age, 49.2; mean BMI, 29.7) were recruited from a thyroid clinic. Ten female controls (mean age, 50.2; mean BMI, 29.7) also participated in the study.

Increased incremental doses of L-thyroxin were used. Indices of vascular stiffness and left ventricular echocardiographic function were measured. Baseline augmentation gradient was elevated in SCH compared to controls, 10.3 mm Hg vs 8.0 mm Hg, (P < 0.05). When the patients were euthyroid the augmentation gradient fell to 8.8 mm Hg, (P = 0.05.) the heart rate augmentation index was 26.7 vs. 18.8 (P = 0.02) falling to 19.7 after treatment (P < 0.001). Mean time of travel of the reflected wave was 139.3 msec in SCH subjects compared to 141.5 msec in controls. After treatment, time of travel of the reflected wave in treated patients increased to 144.9 msec. There were no differences in resting global, regional left ventricular function, or regional myocardial velocities during maximal dobutamine stress between SCH patients and controls or in treated patients compared to baseline.

The authors concluded arterial stiffness was increased in SCH and improved with L-thyroxin, which may be beneficial, whereas myocardial functional reserve was similar to controls and remained unaltered after treatment.


The authors note that "SCH can be seen as a stage in the development of overt hypothyroidism (OH)." The incidence of OH is 38 times higher in patients with SCH and thyroid antibodies than in subjects with normal thyroid function and no antibodies.1 However, other studies demonstrate that some patients with SCH do not progress and may return to normal thyroid function. Therapeutic trials to improve dyslipidemia have been conflicting and the benefit of treatment is unclear. However, one large study of 2856 participants indicated that SCH is associated with ischemic heart disease and might affect all-cause mortality in men.2

The Colorado thyroid disease prevalence study3 is relevant in that it indicates how prevalent the problem is and the difficulty of maintaining euthyroid status in treated patients.

Thyroid function was measured in 1995 participants in a statewide health fair. "The prevalence of elevated TSH levels (normal range, 0.3-5.1 mIU/L) was 9.5% and prevalence of decreased TSH levels was 2.2%. Forty percent of the patients taking thyroid medications had abnormal TSH levels." Lipid levels increased in a graded fashion as thyroid function declined. The lipid levels in subjects with TSH values between 5.1 and 10 mIU/L were significantly greater than corresponding levels in euthyroid subjects.

As the Colorado study demonstrated, it is difficult to recommend treatment of individuals with SCH if a significant number are not going to be successfully brought into the euthyroid range.

The major endocrine and thyroid societies formed a joint task force to make recommendations for treatment. However, they could not make treatment recommendations, since there was no evidence that treatment improved morbidity or mortality.4

Thyroid therapy is not simple! Physicians need to test patients more frequently. and inform the patients to use one brand of L-thyroxin consistently. In addition, thyroxin absorption is decreased when taken with meals and some medications.

My own approach is to treat those patients with high titers of thyroid antibodies and to monitor those without significant titers. The patients need thorough education on the use of thyroid and the need for follow up.

Without any treatment plan we are left with N.Y. Yankee legend Yogi Berra's approach: "When you get to a fork in the road, take it!"


1. Vanderpump MP, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995;43:55-68.

2. Imaizumi M, et al. Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J Clin Endocrinol Metab. 2004:89:3365-3370.

3. Canaris GJ. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:526-534.

4. Surks MI, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291:228-238.