Endocrine hormone imbalance in heart failure with reduced ejection fraction: A cross‐sectional study

Background and Aims Sustained neurohormonal activation plays a central role in the progression of heart failure (HF). Other endocrine axes may also be affected. It was the aim of this study to examine the endocrine profile (thyroid, parathyroid, glucocorticoid, and sex hormones) in a contemporary sample of patients with HF and reduced ejection fraction (EF) on established disease-modifying therapy. Methods This study prospectively measured morning fasting hormones in 52 ambulatory and stable HF patients with EF < 50% on disease-modifying therapy (mean age 63 +/- 11 years, 29% female, mean LVEF 32 +/- 9.6%) and compared them to 54 patients at elevated risk for HF (61 +/- 12 years, 28% female) and 62 healthy controls (HC; 61 +/- 13 years, 27% female). Main comparisons were performed using one-way analysis of variance. Associations with biomarkers were studied with linear regression. Results HF patients showed a reduced free triiodothyronine (fT3)/free thyroxine (fT4) ratio compared to HC (0.30 +/- 0.06 vs. 0.33 +/- 0.05, p = 0.046). Parathyroid hormone (PTH) and cortisol were increased in HF compared to both HC (median [IQR] 59 [50-84] vs. 46 [37-52] ng/L, p < 0.001 and 497 +/- 150 vs. 436 +/- 108 nmol/L, p = 0.03, respectively) and patients at risk (both p < 0.001). Total testosterone was reduced in male HF compared to HC (14.4 +/- 6.6 vs. 18.6 +/- 5.3 nmol/L; p = 0.01). No differences in TSH, estradiol, progesterone, and prolactin were found. Lower fT3 levels were found in HF with EF < 40% versus EF 40%-49% (4.6 +/- 0.3 vs. 5.2 +/- 0.7 pmol/L, p = 0.009). In HF patients, fT3 was an independent predictor of NT-proBNP and high-sensitivity troponin T in multiple regression analysis. PTH was positively associated with NT-proBNP. Conclusion There is evidence of endocrine hormonal imbalance in HF with reduced EF beyond principal neurohormones and despite the use of disease-modifying therapy.