Conference Coverage

Subclinical hypothyroidism may be associated with increased cancer risks



– There is no consistent evidence to suggest that subclinical hypothyroidism is linked to an increased risk of incident breast, prostate, or colon cancer. The condition, however, may be linked to an increased risk of thyroid malignancy and to an increased risk of overall cancer mortality.

Dr. Yu, an endocrinologist at McGill University, Montreal, Quebec, Canada

Dr. Oriana Yu

These findings come from the first systematic review to examine the effect of subclinical hypothyroidism on the risk of incident cancer and cancer mortality.

“Subclinical hypothyroidism is very prevalent,” lead study author Oriana Yu, MD, MSc, said in an interview at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “It affects up to 10% of people, yet at this time we are uncertain as to whether or not [we should] treat them. Most studies have focused on cardiovascular outcomes, because we know that thyroid hormone is very important in lipid metabolism.”

Dr. Yu, an endocrinologist at McGill University, Montreal, and her colleagues searched the Ovid MEDLINE database for articles published from the date of its inception until Nov. 13, 2017, and combined words related to thyroid function and cancer in their search. They limited the analysis to randomized clinical trials and cohort and case-control studies in which the thyroid dysfunction chronologically preceded the cancer incidence or mortality by at least one year.

Of the 180 records screened, 51 full-text articles were assessed for eligibility. Of those, nine met the criteria for systematic review – seven related to cancer risk and two to cancer mortality. The studies were deemed to be of good to medium quality, but six of the nine were cohort studies, the rest case-control studies. “We had hoped to do a systematic review and meta-analysis, but there was high heterogeneity in the studies, especially in terms of different risk measures and outcomes reported,” Dr. Yu said. “As a result, we were not able to perform a meta-analysis.”

The researchers found that the studies had inconsistent findings when it came to the impact of subclinical hypothyroidism on the risk of breast, prostate, and colon cancer. For example, one prospective cohort study of 2,738 patients found no association between subclinical hypothyroidism and the risk of breast cancer (odds ratio, 1.9; 95% confidence interval, 0.8-4.9; Thyroid. 2005;15[11]:1253-9). Women with breast cancer, however, were more likely to have thyroid autoantibodies.

Meanwhile, a case-control study of 1,201 men found that those with elevated TSH levels had a decreased risk of prostate cancer (OR, 0.71; 95% CI, 0.47-1.06; PLoS One. 2012 Oct 30. doi: 10.1371/journal.pone.0047730). “That was a bit surprising to us,” Dr. Yu said. In addition, a nested case-control study of 103,044 patients found that subclinical hypothyroidism was linked to an increased risk for colon cancer (OR, 1.16; 95% CI, 1.08-1.24; J Natl Cancer Inst. 2015 Apr 8. doi: 10.1093/jnci/djv084).

Of the two studies that focused on cancer mortality, one retrospective cohort analysis of 4,735 patients showed that treatment of subclinical hypothyroidism was associated with a decreased risk of cancer mortality in those aged 40-70 years (hazard ratio, 0.59; 95% CI, 0.21-0.99; Arch Intern Med. 2012;172[10]:811-7). The other study, a retrospective cohort analysis of 115,746 patients, found that subclinical hypothyroidism was associated with an increased risk of cancer mortality (relative risk, 1.51; 95% CI, 1.06-2.15; PLoS One. 2015 Apr 1. doi: 10.1371/journal.pone.0122955).

“We need to interpret the cancer-related mortality findings with caution,” Dr. Yu said. “There’s concern about whether patients who are treated might be [generally] healthier or were less frail, compared with those who were not treated. Although these studies adjusted for a number of confounders, it may be difficult to measure and adjust for [those two] factors. That might explain the findings in the two studies on cancer-related mortality.”

Dr. Yu and two coauthors have received salary awards from the Fonds de recherche du Québec–Santé.

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