Hormonal crossroads of the heart: from classic endocrine regulation to cardiac hormone secretion: an updated review.

BACKGROUND: The concept of the heart as both a target and source of hormones has reshaped cardiovascular and endocrine medicine. Classic endocrine axes—including pituitary, thyroid, adrenal, and gonadal hormones, govern cardiac growth, contractility, metabolism, and stress adaptation. Endocrine disorders such as thyroid dysfunction, Cushing’s syndrome, acromegaly, diabetes, and obesity frequently present with distinct cardiovascular phenotypes. Conversely, cardiac disease induces systemic endocrine disturbances, from low T3 syndrome to insulin resistance and hypogonadism, underscoring a bidirectional relationship. OBJECTIVE: To highlight the bidirectional regulatory loops that link the heart with endocrine systems, including aldosterone and the renin–angiotensin–aldosterone system (RAAS), cardiac natriuretic peptides, and sympathetic nervous system interactions, and to emphasize the clinical implications of cardiac neurohormones and cardiokines. METHODS: Narrative synthesis of mechanisms describing aldosterone activity, RAAS signaling, natriuretic peptide pathways, sympathetic activation, catecholaminergic regulation, and endocrine–autonomic balance, together with the role of cardiokines in vascular homeostasis, myocardial remodeling, metabolism, inflammation, and biomarker application. RESULTS: Aldosterone, produced by the adrenal cortex, physiologically supports sodium balance and vascular tone, while chronic RAAS activation promotes myocardial fibrosis, hypertrophy, and adverse remodeling. Cardiac natriuretic peptides attenuate aldosterone synthesis and RAAS signaling, illustrating a key bidirectional loop between the heart and adrenal gland. Catecholamines acutely support cardiac output through β-adrenergic stimulation, whereas chronic sympathetic overactivation promotes hypertrophy, arrhythmias, and adverse remodeling. Cardiac neurohormones and cardiokines, including adrenomedullin, apelin/elabela, FGF21, GDF15, IL-33/ST2, C1q/TNF-related protein 9, and CTRP9, modulate vascular homeostasis, metabolism, inflammation, and remodeling. These mediators serve as clinically relevant biomarkers (BNP/NT-proBNP, sST2, GDF15, FGF21) that improve diagnosis, risk stratification, and therapeutic guidance in heart failure. Interpretation requires consideration of confounders such as obesity, diabetes, chronic kidney disease, atrial fibrillation, and ARNI therapy. Advances in translational research include ARNI and cyclic GMP-targeted drugs, while genetic determinants of NPPA/NPPB and omics technologies are expanding future precision medicine approaches. CONCLUSIONS: Appreciating the integrative endocrine–cardiac axis enriches pathophysiological understanding and opens new avenues for biomarker-guided management and hormone-based therapies. Progress requires close collaboration between endocrinologists, internists, and cardiologists.