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Hypothyroidism increases metabolic syndrome risk in apparently healthy women
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Worsening insulin resistance and higher cardiovascular disease risk were found in apparently healthy women with subclinical hypothyroidism, study data show.
“Women with subclinical hypothyroidism — or even euthyroid but with [thyroid-stimulating hormone] that are along the high normal range — had a greater prevalence of cardiometabolic abnormalities that carry increased risk that is not necessarily picked up by standard lipid tests,” Samia Mora, MD, of the Center for Lipid Metabolomics, cardiovascular division, division of preventive medicine at Brigham and Women’s Hospital, Harvard Medical School, told Endocrine Today.
Mora, Paulo H.N. Harada, MD, MPH, PhD, a research collaborator at Hospital Universitário at University of São Paulo in Brazil, and a research collaborator at the division of preventive medicine at Brigham and Women’s Hospital, and colleagues evaluated data from the Women’s Health Study on 3,914 women without CVD selected for thyroid function analysis to determine cardiometabolic biomarkers among women with subclinical hypothyroidism, overt hypothyroidism and euthyroidism. Overall, 3,321 participants were not on lipid-lowering therapy; 77.4% were euthyroid, 17.3% had subclinical hypothyroidism and 5.3% had overt hypothyroidism.
Participants with subclinical hypothyroidism or overt hypothyroidism were older, had higher BMI and blood pressure, were more likely to be postmenopausal and to have metabolic syndrome and were less likely to be a current smoker compared with euthyroid participants.
Lower HDL cholesterol, higher triglycerides, higher apolipoprotein B concentrations, higher triglyceride/HDL ratios and ApoB/ApoA-I were found among participants who went from euthyroid status to subclinical hypothyroidism or overt hypothyroidism. A trend was found toward increasing insulin resistance when going from euthyroid status to subclinical hypothyroidism or overt hypothyroidism. Mean high sensitivity C-reactive protein levels increased in all participants.
An increasing prevalence of metabolic syndrome was found with the transition from euthyroid status to hypothyroidism (P < .001). The risk for metabolic syndrome was increased with subclinical hypothyroidism (adjusted OR = 1.37; 95% CI, 1.08-1.73) and overt hypothyroidism (adjusted OR = 1.88; 95% CI, 1.3-2.72) compared with euthyroid status. The odds for metabolic syndrome increased with increasing thyroid-stimulating hormone within euthyroid and subclinical hypothyroidism in reference to TSH in the bottom quintile (P for trend = .001).
“Increasing TSH levels along the euthyroid/normal range and subclinical hypothyroidism are potentially associated with increasing risk for incident type 2 diabetes or CV events in a graded manner,” Harada told Endocrine Today. “In our observational study, we cannot prove causality. However, the potential clinical consequences of thyroid hypofunction is highly relevant to the intense debate around the ideal reference TSH or euthyroid range. As the euthyroid and subclinical hypothyroid range comprise the absolute majority of adult women, even a small increase in relative risk related to increasing TSH may potentially translate into high population impact. Our study also raises the hypothesis that insulin resistant dyslipoproteinemia may mediate the potential risk for type 2 diabetes and CV events related to thyroid dysfunction along the TSH spectrum.”
Mora added that clinicians should check for subclinical hypothyroidism in middle-aged and older women even when they are asymptomatic.
“The study also alerts clinicians to the finding that a ‘normal’ TSH within the euthyroid range is not necessarily a clean bill of health and higher TSH values within the normal range may be an alert to early cardiometabolic derangements that are not picked up by the standard LDL cholesterol or total cholesterol tests.” – by Amber Cox
For more information:
Paulo H. N. Harada, MD, MPH, PhD, can be reached at pharada@mail.harvard.edu.
Samia Mora, MD, MHS, can be reached at smora@partners.org.
Disclosure: Harada reports no relevant financial disclosures. Mora reports receiving research grant support from Atherotech Diagnostics and the NIH, serving as a consultant for Amgen, Cerenis Therapeutics, Lilly, Pfizer and Quest Diagnostics and a being a co-inventor on a patent on the use of NMR-measured GlycA for predicting the risk of colorectal cancer. Please see the full study for a list of all other authors’ relevant financial disclosures.
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