A review of the evidence for and against increased mortality in hypothyroidism

• Published in: Nature reviews. Endocrinology Vol. 8; no. 7; pp. 417 - 424
• Main Authors: Thvilum, Marianne, Brandt, Frans, Brix, Thomas H., Hegedüs, Laszlo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-07-2012; Nature Publishing Group
• Subjects: 692/699/2743/1841; 692/700/139; Analysis; Cardiovascular disease; Denmark; Endocrinology; Health aspects; Humans; Hypertension; Hypothyroidism; Hypothyroidism - complications; Hypothyroidism - drug therapy; Hypothyroidism - mortality; Hypothyroidism - physiopathology; Medicine; Medicine & Public Health; Morbidity; Mortality; review-article; Risk factors; Thyroid gland; Thyroxine - therapeutic use; Denmark
• ISSN: 1759-5029; 1759-5037
• DOI: 10.1038/nrendo.2012.29

Hypothyroidism has been linked with cardiac dysfunction, atherosclerosis, hypertension and coagulopathy, and this increased morbidity might be expected to shorten lifespan. However, the relationship between hypothyroidism and mortality is not clear, particularly regarding overt hypothyroidism. This Review discusses the literature on mortality in patients with hypothyroidism, appraises the weaknesses of existing studies and suggests new directions for research that could improve our understanding of the relationship between hypothyroidism and lifespan.
The lifetime risk of overt hypothyroidism is around 5%, and this disease is usually preceded by subclinical hypothyroidism, which has an even higher prevalence (estimated to be up to 9%). Hypothyroidism has been linked with cardiac dysfunction, atherosclerosis, hypertension and coagulopathy. Intuitively, this increased morbidity is expected to shorten patients' lifespan, but definitive data are lacking on whether either of these hypothyroid states (particularly overt hypothyroidism) increase mortality. Study findings are inconsistent and, overall, the pooled data do not demonstrate increased mortality in patients with either subclinical or overt hypothyroidism. However, none of the available studies was adequately designed to answer this question. This Review discusses major shortcomings in those studies, such as population dissimilarities, hypothyroid state classification and misclassification, the inclusion of nonthyroidal illness, drug interference from concurrent therapies, serious comorbidities (for example, cardiovascular disease), differences in duration of follow-up and the number of levothyroxine-treated individuals. Taken together, the data exhibit little evidence of systematic bias and no strong scientific proof of increased mortality related to either subclinical or overt hypothyroidism. Future studies, however, should take the above-mentioned shortcomings and potential genetic confounding into consideration.
Key Points
Hypothyroidism is associated with increased morbidity, such as hypertension and coronary heart disease
Published data do not unequivocally support an increased risk of mortality in individuals with either subclinical or overt hypothyroidism
Interpretation of the study results relating to this association is complicated by considerable variation in their methodology
Previous studies were not designed to determine whether subclinical or overt hypothyroidism increase mortality risk; one important confounding factor is that many patients are treated with levothyroxine
Future research should include adequately powered, long-term follow-up studies of cohorts with clearly defined diagnoses of thyroid diseases and account for genetic and environmental confounding variables