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Risk of Coronary Heart Disease and Mortality for Adults With Subclinical Hypothyroidism

Mario Rotondi, MD, PhD; Flavia Magri, MD, PhD; Luca Chiovato, MD, PhD
JAMA. 2010;304(22):2481-2482. doi:10.1001/jama.2010.1786
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To the Editor: In their study, Dr Rodondi and colleagues1 addressed the issue of the relationship between subclinical hypothyroidism and coronary heart disease (CHD) or mortality. Previous large prospective cohort studies have provided conflicting results about this extensively studied association. In the study by Rodondi et al, an attempt to reduce the effects of several confounders (including age, sex, degree of thyroid stimulating hormone [TSH] elevation, and pre-existing cardiovascular disease) was performed.1 However, the finding of no association of risk with subclinical hypothyroidism for TSH concentration up to 10.0 mIU/L may be flawed because it did not provide information about the body mass index (BMI) of the patients diagnosed with subclinical hypothyroidism.

This might be a problem because subclinical hypothyroidism, especially when characterized by minor increases in serum TSH levels, is frequently observed among obese patients.2 4 The elevated serum TSH found in obese (and particularly in morbidly obese) patients may be a mere consequence of the excess body weight rather than a condition of primary thyroid failure.2 4 This concept would imply that obese patients with a moderate elevation in serum TSH would not experience increased systemic vascular resistance, altered endothelial function, increased atherosclerosis, altered coagulability, and lipid abnormalities, which account for the increased risk of CHD associated with subclinical hypothyroidism.5

Positive tests for thyroid autoantibodies are the only parameters able to discriminate between true subclinical hypothyroidism and obesity-induced hyperthyrotropinemia.3 Because thyroid antibodies were not taken into account in diagnosing subclinical hypothyroidism in the study by Rodondi et al, the conclusions may have been biased. Indeed, obese patients with a moderately increased TSH (up to 10 mIU/L) may include a subgroup of patients who are not truly hypothyroid, thus underestimating the real CHD risk associations of subclinical hypothyroidism (defined as high serum level of TSH with normal free thyroxine levels and positive test results for thyroid antibodies).

AUTHOR INFORMATION

Financial Disclosures: None reported.

REFERENCES

Rodondi N, den Elzen WP, Bauer DC,  et al; Thyroid Studies Collaboration.  Subclinical hypothyroidism and the risk of coronary heart disease and mortality.  JAMA. 2010;304(12):1365-1374
PubMed
Reinehr T, de Sousa G, Andler W. Hyperthyrotropinemia in obese children is reversible after weight loss and is not related to lipids.  J Clin Endocrinol Metab. 2006;91(8):3088-3091
PubMed
Rotondi M, Leporati P, La Manna A,  et al.  Raised serum TSH levels in patients with morbid obesity: is it enough to diagnose subclinical hypothyroidism?  Eur J Endocrinol. 2009;160(3):403-408
PubMed
Reinehr T. Obesity and thyroid function.  Mol Cell Endocrinol. 2010;316(2):165-171
PubMed
Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction.  Endocr Rev. 2008;29(1):76-131
PubMed

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Rodondi N, den Elzen WP, Bauer DC,  et al; Thyroid Studies Collaboration.  Subclinical hypothyroidism and the risk of coronary heart disease and mortality.  JAMA. 2010;304(12):1365-1374
PubMed
Reinehr T, de Sousa G, Andler W. Hyperthyrotropinemia in obese children is reversible after weight loss and is not related to lipids.  J Clin Endocrinol Metab. 2006;91(8):3088-3091
PubMed
Rotondi M, Leporati P, La Manna A,  et al.  Raised serum TSH levels in patients with morbid obesity: is it enough to diagnose subclinical hypothyroidism?  Eur J Endocrinol. 2009;160(3):403-408
PubMed
Reinehr T. Obesity and thyroid function.  Mol Cell Endocrinol. 2010;316(2):165-171
PubMed
Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction.  Endocr Rev. 2008;29(1):76-131
PubMed
December 8, 2010
Nicolas Rodondi, MD, MAS; Douglas C. Bauer, MD; Jacobijn Gussekloo, MD, PhD
JAMA. 2010;304(22):2481-2482.
December 8, 2010
Noboru Takamura, MD, PhD; Naomi Hayashida, MD, PhD; Takahiro Maeda, MD, PhD
JAMA. 2010;304(22):2481-2482.
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