The Two Faces of Janus: Why Thyrotropin as a Cardiovascular Risk Factor May Be an Ambiguous Target.

Elevated concentrations of free thyroid hormones are established cardiovascular risk factors, but the association of thyrotropin (TSH) levels to hard endpoints is less clear. This may, at least in part, ensue from the fact that TSH secretion depends not only on the supply with thyroid hormones but on multiple confounders including genetic traits, medication and allostatic load. Especially psychosocial stress is a still underappreciated factor that is able to adjust the set point of thyroid function. In order to improve our understanding of thyroid allostasis, we undertook a systematic meta-analysis of published studies on thyroid function in post-traumatic stress disorder (PTSD). Studies were identified via MEDLINE/PubMed search and available references, and eligible were reports that included TSH or free thyroid hormone measurements in subjects with and without PTSD. Additionally, we re-analyzed data from the NHANES 2007/2008 cohort for a potential correlation of allostatic load and thyroid homeostasis. The available evidence from 13 included studies and 3386 euthyroid subjects supports a strong association of both PTSD and allostatic load to markers of thyroid function. Therefore, psychosocial stress may contribute to cardiovascular risk via an increased set point of thyroid homeostasis, so that TSH concentrations may be increased for reasons other than subclinical hypothyroidism. This provides a strong perspective for a previously understudied psychoendocrine axis, and future studies should address this connection by incorporating indices of allostatic load, peripheral thyroid hormones and calculated parameters of thyroid homeostasis.

Usefulness of Serum Free Thyroxine Concentration to Predict Ventricular Arrhythmia Risk in Euthyroid Patients With Structural Heart Disease.

The aim of the present study was to determine whether free thyroxine (FT4) and calculated thyroid parameters predict the incidence of ventricular arrhythmias in euthyroid heart failure patients with implantable cardioverter-defibrillators (ICD). In this open-label prospective cohort study, 115 consecutive euthyroid patients (mean age 62.9 ± 1.3 years; 87% male; ischemic cardiomyopathy 63%) scheduled for primary prevention ICD implantation or exchange were enrolled. Serum concentrations of thyrotropin (thyroid-stimulating hormone) and FT4 were measured 1 day before device operation. Primary and secondary end points were defined as occurrence of appropriate ICD therapy (AIT) and cardiovascular death, respectively. During a mean follow-up of 1,191 ± 35 days, 24 patients (21%) experienced AIT, and cardiovascular death was observed in 10 patients (9%). Patients with AIT had higher FT4 concentrations compared with those without AIT (18.9 ± 0.48 vs 16.2 ± 0.22 pmol/L, p <0.001). FT4 was an independent predictor of AIT in an adjusted Cox regression (hazard ratio = 1.47, p <0.001). Kaplan-Meier analysis demonstrated that Jostel's thyroid-stimulating hormone index, reflecting the central component of the hypothalamus-pituitary-thyroid loop, and SPINA-GT as surrogate markers for thyroid's secretory capacity predicted AIT incidences. None of the indices predicted cardiovascular death. In conclusion, FT4 concentration predicts an increased incidence of ventricular arrhythmias in euthyroid patients receiving ICDs for primary prevention. Our data suggest that both impending primary hyperthyroidism and an increased thyroid homeostasis set point may increase the rate of AIT in this patient population.