Sample Timing, Diagnosis of Subclinical Thyroid Dysfunction and Mortality in Acute Myocardial Infarction: ThyrAMI1 Study

Abstract

Objective The objective of this study was to determine the impact of blood sample timing on the diagnosis of subclinical thyroid dysfunction (SCTD) and mortality in patients with acute myocardial infarction (AMI). Patients, Design, and Main Outcome Measures Patients with AMI had thyroid function evaluated on admission between December 2014 and December 2016 and those with abnormal serum thyrotropin (TSH) had repeat thyroid function assessed at least a week later. The association between sample timing and SCTD was evaluated by logistic regression analysis. Secondary outcomes were confirmation of SCTD on repeat testing and all-cause mortality up to June 2018. Results Of the 1806 patients [29.2% women, mean (± standard deviation) age of 64.2 (±12.1) years] analyzed, the prevalence of subclinical hypothyroidism (SCH) was 17.2% (n = 311) and subclinical hyperthyroidism (SHyper) was 1.2% (n = 22) using a uniform TSH reference interval. The risk of being diagnosed with SCTD varied by sample timing in fully-adjusted models. The risk of SCH was highest between 00.01 and 06.00 hours and lowest between 12.01 and 18.00 hours, P for trend <.001, and risk of SHyper was highest between 12.01 hours and 18.00 hours and lowest between 00.01 hours and 06.00 hours. Furthermore, time of the initial sample was associated with the risk of remaining in a SCH state subsequently. Mortality in SCH patients was not elevated when a uniform TSH reference interval was utilized. However, when time period–specific TSH reference ranges were utilized, the mortality risk was significantly higher in SCH patients with HR (95% CI) of 2.26 (1.01–5.19), P = .04. Conclusions Sample timing impacts on the diagnosis and prognosis of SCH in AMI patients. If sample timing is not accounted for, SCH is systemically misclassified, and its measurable influence on mortality is lost.

Management of Hypothyroidism in Patients with Acute Myocardial Infarction

“…The median initial TSH level was 20 mIU/L, with higher values in the OH group (42 vs. 14 mIU/L). Patients who received treatment had a higher TSH (25 mIU/L, IQR, 13-43) when compared to those who did not receive LT4 treatment (12 mIU/L, IQR, [11][12][13][14][15][16][17][18][19], (p = 0.007). In the group of patients that were not treated with LT4, 50% were hemodynamically unstable at baseline when compared to the 21% of those who were treated.…”

“…In terms of diagnosis, the response changes in the thyroid axis as a reaction to acute illness can limit the ability of thyroid testing to assess thyroid function and guide management decisions. The timing of the TSH sample as it relates to the AMI and time of the day has been associated with variable TH levels [17,18]. For example, a study of 47 patients without previous use of TH admitted with AMI, noted a decrease in total T3 (~19% at 24-26 hours when compared to a sample that was obtained during the first 6 hours) and TSH levels (~51%, when comparing similar timeframes).…”

“…For example, a prospective study including 400 patients without previous LT4 treatment admitted for management of acute coronary heart disease found that, although most of the patients were euthyroid (77%), 8% had OH and 3% SCH [16]. A larger multicenter study, including 1806 patients, found a prevalence of SCH of 17%, after excluding 6% of patients who were on TH replacement [17].…”

“…In the acute state, most patients are found to have a downregulation of TH that seems to occur rapidly, usually in the first few days after the event [18]. In fact, 5-35% of patients with an AMI are found to have low T3 syndrome (low T3 concentrations that are associated with normal/mildly reduced serum T4 and TSH levels and increased reverse T3 levels) [6,17,19,20].…”

Prevalence, predictors and outcomes of thyroid dysfunction in patients with acute myocardial infarction: the ThyrAMI-1 study

“…This understanding may help to prevent inappropriate diagnoses being made and unnecessary treatments being initiated [11]. A previous analysis of participants presenting with AMI demonstrated that sample timing has a significant impact on the diagnosis and prognosis of subclinical thyroid disease (SCTD) [12]. Therefore, it is important to study the prevalence of thyroid dysfunction in AMI patients and understand factors associated with these biochemical abnormalities.…”