The influence of stress and cortisol on thyroid dysfunction

Chronic stress and sustained activation of the hypothalamic-pituitary-adrenal (HPA) axis result in elevated cortisol secretion, which caninterfere with regulation of the hypothalamic-pituitary-thyroid (HPT) axis and affect thyroid hormone metabolism and immune-mediatedmechanisms. The aim of this review is to present current evidence on the influence of stress and cortisol on thyroid function, including their effects onthe HPT axis, peripheral thyroid hormone metabolism, and autoimmunity, and to discuss potential clinical implications. A comprehensive literature search was conducted covering the last decade's clinical, population-based, and experimental studies addressingthe associations between psychological stress, cortisol levels, thyroid axis dysregulation, deiodinase activity, and autoimmune thyroiddisease. Mechanistic pathways and therapeutic perspectives are summarized. Evidence indicates that cortisol suppresses TRH and TSH secretion and disrupts the circadian rhythm of TSH secretion, while also influencingthyroid hormone transport proteins and deiodinase activity (↓ D1/↓ D2, ↑ D3), leading to reduced T3 and increased rT3. Thesemechanisms contribute to subclinical hypothyroidism and the non-thyroidal illness syndrome (NTIS) phenotype. Chronic stress alsodisturbs immune homeostasis (Treg/Th17 imbalance, elevated IL-6, TNF-α), increasing susceptibility to autoimmune thyroid diseases suchas Hashimoto's thyroiditis and Graves' disease. Emerging data suggest that stress-reduction interventions, optimization of micronutrientstatus (selenium, vitamin D, zinc), and modulation of the HPA axis may complement standard thyroid therapy. Stress and cortisol are significant but often underrecognized moderators of thyroid regulation through endocrine, metabolic, and immunologicalpathways. Incorporating assessment of chronic stress and HPA-axis activity into the diagnostic workup of thyroid disordersmay enhance clinical evaluation, and stress-targeted adjunctive interventions may improve management, particularly in patients withautoimmune thyroid disease.