Endocrine Feedback Failure describes the pathological inability of a hormonal system to appropriately adjust its secretory rate in response to circulating hormone levels or downstream physiological effects. This breakdown in the negative or positive feedback loop, which is central to endocrine regulation, leads to chronic hyper- or hyposecretion and subsequent systemic dyshomeostasis. The failure can originate at the level of the target gland, the pituitary, or the hypothalamus, resulting in a persistent and often progressive hormonal imbalance. Clinical symptoms manifest as the body loses its ability to self-regulate essential physiological processes.
Origin
This concept is derived directly from the fundamental principles of endocrinology, which is built upon the model of physiological control systems and feedback loops. The term ‘failure’ highlights the pathological deviation from the normal, self-correcting function of the endocrine axis. Its understanding is crucial for differentiating primary gland disorders from central (pituitary or hypothalamic) regulatory issues.
Mechanism
Normally, the mechanism involves secreted hormones acting on receptors in the pituitary or hypothalamus to inhibit (negative feedback) or stimulate (positive feedback) further release of upstream trophic hormones. Failure occurs when these receptor sites become desensitized, the signaling pathways are disrupted, or the producing gland itself is damaged and cannot respond to trophic signals. For example, adrenal exhaustion can lead to a failure of cortisol to appropriately suppress ACTH release, resulting in persistent HPA axis dysregulation.
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