Sample Timing Significantly Affects Diagnosis of Subclinical Thyroid Dysfunction in Acute Myocardial Infarction

Time of thyroid function sampling may affect the diagnosis of subclinical thyroid dysfunction in patients with acute myocardial infarction, according to study results published in The Journal of Endocrinology & Metabolism.

The diagnosis of primary thyroid dysfunction is based on abnormal thyroid-stimulating hormone (TSH) level with circulating thyroid hormone (thyroxine [T₄] and triiodothyronine [T₃]) levels within the reference range. There are conflicting reports regarding the association between subclinical hypothyroidism and hyperthyroidism and cardiovascular disease and mortality.

Many factors may affect serum TSH, including age, sex, smoking status, body mass index, iodine status, thyroid peroxidase antibody status, type of assay used, medication use, and concurrent illness. In addition, sampling time of TSH may also be important, as TSH is characterized by a recognized circadian rhythm, with peak levels in early morning and nadir in the afternoon.

Previous studies have reported that the circadian pattern of TSH secretion may be altered under various circumstances. The goal of the current study was to assess whether timing of TSH sampling in patients with acute myocardial infarction has a significant effect on the diagnosis of subclinical thyroid disease and adverse outcomes.

The Thyroxine in Acute Myocardial Infarction trial was a prospective multicenter study that included patients with acute myocardial infarction treated in 6 cardiac centers in England between December 2014 and December 2016.

The study cohort included 1806 participants (29.2% women; mean age, 64.2 years) with abnormal serum TSH. Of these patients, 311 (17.2%) were diagnosed with subclinical hypothyroidism and 22 (1.2%) were diagnosed with subclinical hyperthyroidism.

Serum TSH and free T₃ levels were highest between 12:01 and 6 AM and lowest between 12:01 and 6 PM, while free T₄ levels were not significantly different. For that reason, diagnosis of subclinical hypothyroidism was highest in the 12:01 to 6 AM period (20.9%) and lowest in the 12:01 to 6 PM period (8.7%). In contrast, the prevalence of subclinical hyperthyroidism was lowest between 12:01 and 6 AM (0.7%) and highest between 12:01 and 6 PM (2.5%).

Using sample timing as a continuous variable over 24 hours, the researchers noted a significant relationship between serum TSH and free T₃ levels and time of sample. Sample timing was also linked to thyroid dysfunction. Risk of being diagnosed with subclinical hypothyroidism was higher in the 12:01 to 6 AM timeframe, while risk of being diagnosed with subclinical hyperthyroidism was higher from 12:01 to 6 PM. There was no significant association between time of sampling and free T₄ levels.

Time of sampling also affected subsequent rates of normalization of serum TSH levels in patients with acute myocardial infarction who underwent repeat thyroid function tests (n=308). In the baseline subclinical hypothyroidism group, 58% of patients had normalized serum TSH with repeat testing from 12:01 to 6 AM compared with 28% of those with testing from 12:01 to 6 PM (P <.001). No statistical analysis was completed for patients with subclinical hyperthyroidism because of the small number of cases.

Mortality in patients with subclinical hypothyroidism was not elevated when a uniform TSH reference interval was used. However, mortality was significantly higher in patients with subclinical hypothyroidism when categorization was done using a time-period-specific reference interval (hazard ratio, 2.26; 95% CI, 1.01-5.19; P =.04). Mortality in the group of patients with subclinical hyperthyroidism was similar to that of individuals in the control group with normal thyroid function.

The researchers acknowledged several study limitations, including using different assays to evaluate some of the thyroid function parameters and missing data on recurrent cardiovascular events. Furthermore, the results are limited to patients with acute myocardial infarction.

“Our findings are important for interpretation of TSH levels in clinical practice. They suggest that for an accurate diagnosis of [subclinical thyroid dysfunction], the TSH reference range should take the time of sampling into account. Importantly, using this methodology to interpret the results may provide important prognostic information in patients after [acute myocardial infarction],” concluded the researchers.

Disclosure: One study author disclosed affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Razvi S, Leng O, Jabbar A, et al. Sample timing, diagnosis of subclinical thyroid dysfunction and mortality in acute myocardial infarction: ThyrAMI1 study [published online November 26, 2019]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz143