Cortisol Override describes a physiological state where chronic, excessive secretion of the glucocorticoid cortisol, often secondary to prolonged allostatic load, exerts a dominant, suppressive regulatory influence over other critical endocrine axes. This profound hormonal imbalance results in the functional suppression of the hypothalamic-pituitary-gonadal (HPG) axis and the hypothalamic-pituitary-thyroid (HPT) axis. The clinical manifestation is often a reduction in sex hormone production and a decline in thyroid hormone conversion, prioritizing survival functions over reproductive and metabolic efficiency.
Origin
This concept is rooted in the extensive research on the stress response and the HPA axis’s hierarchical dominance in the endocrine system. It reflects the body’s ancient, adaptive survival mechanism where, under perceived threat (chronic stress), the production of energy-mobilizing and anti-inflammatory hormones like cortisol takes precedence, effectively overriding less immediate functions.
Mechanism
The mechanism involves direct and indirect inhibitory feedback loops. Elevated cortisol directly suppresses the release of Gonadotropin-Releasing Hormone (GnRH) and Thyroid-Releasing Hormone (TRH) from the hypothalamus, subsequently reducing pituitary Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), and Thyroid-Stimulating Hormone (TSH) output. Furthermore, cortisol can inhibit the peripheral conversion of inactive thyroxine (T4) to the active triiodothyronine (T3), creating a state of euthyroid sick syndrome and diminishing metabolic rate.
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