T4 replacement did not improve cognitive function in patients with subclinical hypothyroidism

79th Annual Meeting of the ATA

CHICAGO — Thyroxine therapy had no effect on measures of cognitive therapy in patients with subclinical hypothyroidism, according to recent study findings presented at the 79th Annual Meeting of the American Thyroid Association.

Researchers from Birmingham, United Kingdom, randomly assigned patients aged 65 years or older to thyroxine therapy (n=52) or placebo (n=42) to determine whether using T₄ replacement to achieve biochemical euthyroidism also improved cognitive dysfunction in patients with subclinical hypothyroidism.

In the T₄ group, 82% of patients achieved euthyroidism at six months, and 84% of patients achieved euthyroidism at 12 months.

For the Trailmaking A psychomotor test for executive function, in the T₄ group, values were 45.72 at baseline, 46.54 at six months and 45.33 at 12 months; in the placebo group, values were 50.29, 49.87 and 46.78 (P=.52).

For the Trailmaking B psychomotor test for executive function, in the T₄ group, values were 110.57 at baseline, 104.24 at six months and 100.65 at 12 months; in the placebo group, values were 131.46, 118.24 and 114.11 (P=.95). – by Christen Haigh

Although several previous observational studies have suggested an association between subclinical hypothyroidism and subtle cognitive impairment, treatment with L-thyroxine was not found to improve cognitive function in subclinically hypothyroid subjects as compared with a placebo-treated group. Importantly, 18% and 16% of participants, respectively, had failed to achieve euthyroidism by six months and one year despite thyroid function testing and L-thyroxine dose adjustments every eight weeks. This may have biased results toward the null. In addition, the TSH goal of <5.5 mIU/L may not have been stringent enough.

– Elizabeth N. Pearce, MD

Assistant Professor of Medicine, Boston University School of Medicine

The randomized placebo-controlled trial by Parle et al showing no benefit of thyroid hormone therapy on cognitive function in elderly patients with subclinical hypothyroidism is consistent with other studies suggesting the same thing. Indeed, there is little evidence for abnormal cognition in such patients at baseline, compared with age-matched controls (Lindeman et al. J Am Geriatr Soc. 1999). Furthermore, we are now rethinking our definition of subclinical hypothyroidism and the elderly (Surks et al. J Clin Endocrinol Metab. 2008), and there are even data to suggest that mildly elevated serum TSH levels in individuals older than 85 years of age may be beneficial, rather than harmful. (Gussekloo et al. JAMA. 2004).

– David S. Cooper, MD

Professor of Medicine
Johns Hopkins University School of Medicine, Baltimore

Mini-Mental State Examination values (P=.18)

T4 group Placebo At baseline 28.26 28.17 At six months 29.00 27.82 At 12 months 28.24 28.22

Middlesex Elderly Assessment of Mental State values (P=.57)

T4 group Placebo At baseline 11.72 11.21 At six months 11.56 11.58 At 12 months 11.67 11.60

For more information:

• Parle JV, Franklyn J, Roalfe A, et al. #159. Presented at: 79th Annual Meeting of the American Thyroid Association; Oct. 1-5, 2008; Chicago.