<b>MODEL-BASED REGULATION OF CORTISOL LEVELS IN INDIVIDUALS WITH ADRENAL INSUFFICIENCY</b>

<p dir="ltr">Hypocortisolism, also known as adrenal insufficiency, is a condition that occurs due to a low concentration of cortisol. This hormonal imbalance significantly impacts the body's ability to regulate stress, metabolism, and immune responses. Therefore, it is crucial to maintain cortisol levels within a healthy range. The production of cortisol is governed by the hypothalamus-pituitary-adrenal (HPA) axis, a part of the endocrine system. In response to stress, the hypothalamus secretes corticotropin-releasing hormone (CRH), which stimulates the release of adrenocorticotropic hormone (ACTH) in the pituitary gland. ACTH then travels through the bloodstream to the adrenal glands, where it causes the release of cortisol.</p><p dir="ltr">In this thesis, a novel mathematical model of the HPA axis is proposed that incorporates the endogenous circadian rhythm. This model simulates two conditions of hypocortisolism: primary and secondary adrenal insufficiency.</p><p dir="ltr">Adrenal insufficiency cannot be cured, but it can be treated with cortisol replacement therapy. The standard clinical practice is to prescribe a therapeutic dose of hydrocortisone (HC). To evaluate the effectiveness of this method, an open-loop cortisol replacement strategy with fixed dosage is presented, simulating both conditions of adrenal insufficiency. Although constant dosing strategies show potential, adaptive and personalized treatment strategies are required to maintain hormone levels within a healthy range.</p><p dir="ltr">To address these limitations, a closed-loop controller based on Model Predictive Control (MPC) is designed to optimize cortisol replacement therapy, adhering to the constraints. The controller effectively regulates cortisol levels within an appropriate range for both conditions of adrenal insufficiency. To enhance practical applicability, input doses are quantized for real-world implementation. Thus, this controller can serve as a virtual assistant to physicians in prescribing daily cortisol replacement therapy to regulate cortisol levels in individuals with adrenal insufficiency. </p>