TOPIC:Subclinical hypo- and hyperthyroidism and mortality
Title: Association between increased mortality and mild thyroid dysfunction in cardiac patients.
Authors: Ievarsie G, Molinaro S, Landi P, Taddei MC, Galli E, Mariani F, L-Abbate A, & Pingitore A.
Reference: Archives of Internal Medicine 167: 1526-1532, 2007
The clinical relevance of subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (SCT) is not clear. There is a need for long-term outcome studies to gain more insight.
To evaluate if subclinical hypo-/hyperthyroidism is associated with a higher mortality in cardiac patients.
Included were all 4.368 patients hospitalized in 2000-2005 at the Department of Cardiology in Pisa. Exclusion criteria were acute coronary syndrome, pulmonary oedema, severe systemic diseases, hospital mortality, overt hyper-/hypothyroidism, medications influencing thyroid function, or atypical thyroid state (not fitting in any group described below): based on these criteria, 1.060 patients were excluded. Thyroid function was assessed in a blood sample withdrawn at 07.00 hrs at day 2-5 of the hospital admission. Patients were divided into 4 groups: Euthyroidism (TSH, FT4 & FT3 normal), SCH (TSH: 4.5-10 mU/L), SCT (TSH: <0.3 mU/L), and low T3 (FT3: < 3.2 pmol//L, TSH & FT4 normal). Thyroid function tests were repeated within 2 to 12 weeks and, if this resulted in another classification relative to the first blood sample, these patients were also excluded (N = 187). Finally, the study population comprised 3.121 patients (33% females; mean age: 61 years). The mean follow up period was 32 months.
Cardiac and total mortality was 3.4% & 7.3% respectively in euthyroid patients, 7.2% & 13.0% respectively in SCH, 8.2% & 9.2% respectively in SCT, and finally 6.5% & 13.1% respectively in low T3. After correction for various risk factors, the hazard ratio for cardiac mortality was higher in SCH (RR: 2.40; 95% CI: 1.36-4.21), in SCT (RR: 2.32; 95% CI: 1.11-4.85), and in low T3 (RR: 1.63; 95% CI: 1.14-2.33) than in euthyroidism. Hazard ratio-s for total mortality were higher in SCH (RR: 2.01; 95% CI: 1.33-3.04) and in low T3 (RR: 1.57; 95% CI: 1.22-2.01), but not in SCT.
A mildly altered thyroid status is associated with an increased risk of mortality in patients with cardiac disease.
Limitations of the present study were the absence of thyroid function tests during the follow-up period, the absence of information on non-fatal cardiovascular events, and the lack of analysis of serum TSH levels.
The author-s conclusion, however, seems to be valid from a methological point of view. One of the strengths of present study was that the investigators have classified the etiological diagnoses in all 208 patients with SCH: chronic autoimmune thyroiditis (75%), post-thyroidectomy or post-radioiodine (25%), and in all 98 patients with SCT: multinodular goiter (81%), Graves- disease (15%), and thyroid adenoma (4%). Together with the 910 low T3 patients, this indicates that a slightly abnormal thyroid function was found in 39% of the cardiac patients.
These results are of interest and present potentially a high clinical relevance, provided that it can be demonstrated (in further studies) that medical intervention might diminish the mortality. Such studies, however, on a preventive medical intervention aimed at correcting thyroid abnormalities, have not yet been performed, and would require a rather long follow-up period. Also, it is highly likely that any beneficial effect of medical intervention will be age-dependent, and in this respect a more detailed analysis of the data per decade in the present cohort study could illuminate further our insight. Summary and commentary prepared by Wilmar Wiersinga (related to Chapters 9, 10, & 13 of TDM)