Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

Abstract

Background: Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T₃) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. Methods: Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T₄) and T₃, reverse (r)T₃, 3-iodothyronamine (3-T₁AM) and 3,5-diiodothyronine (3,5-T₂) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. Results: Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T₃ and/or low T₄ syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT₃ concentrations were significantly decreased, but still within their reference ranges. 3,5-T₂ concentrations directly correlated with rT₃ concentrations and inversely correlated with FT₃ concentrations. Furthermore, 3,5-T₂ concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT₃, 3,5-T₂, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. Conclusion: This study confirms reduced FT₃ concentrations in patients with POAF and is the first to report on elevated 3,5-T₂ concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms.

Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function

“…Consequently, such a high pressure system requires defensive mechanisms to protect the cells from the dangers of being flooded and overwhelmed by an over-supply of thyroid hormones. This includes binding of thyroid hormones to plasma proteins, prior activation of the pro-hormone T4 (T4–T3 conversion), gate control at cell entry (active transport across the cell membrane), and production of locally expressed counter-regulatory derivatives such as reverse T3 and thyronamines that exert short loop inhibitory control (17, 24–26). There is additionally a systemic negative feedback control at the pituitary and hypothalamic level that both controls thyroid hormone production and sets an appropriate internal reference point for pituitary TSH secretion (27).…”

Circulating 3-T1AM and 3,5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study

“…Also in cardiac surgery patients, patients with sepsis, liver cirrhosis and brain tumors with NTI, 3,5-T2 concentrations have been reported to be elevated (31,34). Thus, during critical illness, part of T4 and T3 might indeed be metabolized to 3,5-T2.…”

“…The serum concentrations of the metabolites 3-T1AM (23) and 3,5-T2 (28,31) were quantified with in house developed monoclonal-antibody based chemiluminescence immunoassays, partly adapted from previously described. For the 3-T1-AM assay, plates were now coated with 3-T1AM-labelled BSA (50 µg in 0.1 ml per well; overnight at 4°C), instead of coating with a polyclonal rabbit anti-mouse IgG (H&L) as capture antibody, to minimize cross-reactivities between antibodies.…”

“…The 3,5-T2 values were calculated from a logtransformed standard curve of 0.05 to 10 nM as published (28,31). The limit of quantification of the 3,5-T2-assay was 0.2 nM, the limit of detection was 0.05 nM.…”

The Effect of Selenomethionine on Thyroid Autoimmunity in Euthyroid Men With Hashimoto Thyroiditis and Testosterone Deficiency

“…A structure parameter inference approach (SPINA) is a technique derived from an empirical cybernetic model of the pituitary‐thyroid feedback control. Based on equilibrium analysis of a compartmental nonlinear model, this method makes it possible to estimate in vivo the functional status of the thyroid gland from plasma or serum levels of thyrotropin and thyroid hormones determined only once . The structure parameters of thyroid homeostasis—Jostel thyrotropin index, structure parameter interference approach‐GT (SPINA‐GT), and structure parameter interference approach‐GD (SPINA‐GD) were calculated using SPINA‐Thyr 4.0.1 for Mac Universal software, which is available online.…”