By Jane Lewis
Levothyroxine replacement in older patients with subclinical hypothyroidism provides no apparent benefits, reports new research in the New England Journal of Medicine.
According to the authors of the study, subclinical hypothyroidism is ‘a possible contributor to many problems in older persons,’ including subsequent coronary heart disease.
Commenting to Endocrinology Today, Professor Duncan Topliss, Director, Department of Endocrinology and Diabetes at The Alfred, Melbourne, said the research made an important contribution as the largest double-blinded, randomised, placebo-controlled parallel-group trial of thyroid hormone replacement therapy for subclinical hypothyroidism in the elderly to date.
The study featured 737 adults aged 65 years or older (mean age 74.4 years; 53.7% women) who had persisting subclinical hypothyroidism, defined as a thyroid-stimulating hormone (TSH) level of 4.60 to 19.99 mIU/L and free thyroxine level within the reference range. A total of 368 patients were assigned to receive levothyroxine at a starting dose of 50 µg daily (25 µg if the patient had coronary heart disease or weighed under 50 kg).
After one year of treatment (median dose, 50 µg), the mean TSH level had decreased from a baseline level of 6.40±2.01 mIU/L to 3.63±2.11 mIU/L in the levothyroxine group and 5.48±2.48 mIU/L in the placebo group. Also at one year, there was no difference in mean change between the two groups on health-related quality of life, measured by both general and hypothyroidism-specific quality of life validated questionnaires, nor on a wide range of secondary-outcome measures, including hand grip strength and executive cognitive function.
The authors acknowledge that the trial was not powered to detect any effect of levothyroxine on the incidence of cardiovascular events or mortality.
Commenting on clinical implications, Professor Topliss said the existing European Thyroid Association guidelines on treatment of subclinical hypothyroidism – which many Australian endocrinologists have been acting in line with for several years – ‘are already consistent with the results of this trial,’ adding that clinicians should be aware that these results ‘do not apply to women with subclinical hypothyroidism seeking to become, or who are, pregnant.’
Past research has suggested there may be an adverse effect of overtreatment of subclinical hypothyroidism in the elderly, he cautioned [e.g. Taylor PN, et al. JAMA Int Med 2014; 174: 32-39]. ‘Data for the increased risk of harm from subclinical hyperthyroidism are stronger than those for potential benefit from treatment of subclinical hypothyroidism, and the current study reinforces this view,’ he said.
N Engl J Med 2017; doi: 10.1056/NEJMoa1603825.