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    A System-Theoretic Investigation of Hormone Dynamics in Chronic Fatigue Syndrome, Fibromyalgia Syndrome, and Obesity

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    PEDNEKAR-THESIS-2020.pdf (7.808Mb)
    Date
    2020-05
    Author
    Pednekar, Divesh Deepak
    0000-0002-9318-7964
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    Abstract
    Fibromyalgia syndrome (FMS), chronic fatigue syndrome (CFS), and obesity are complicated medical disorders with little known etiologies. The purpose of this research is to characterize FMS, CFS, and obesity by studying the variations in hormonal secretion patterns, timings, amplitudes, the number of underlying pulses, as well as infusion and clearance rates of hormones such as cortisol, and leptin. Employing a physiological state-space model with plausible constraints, we estimate the hormonal secretory events and the physiological system parameters (i.e., infusion and clearance rates). The first outcome of our research shows that the clearance rate of cortisol is lower in FMS patients as compared to their matched healthy individuals based on a simplified cortisol secretion model. Moreover, the number, magnitude, and the energy levels of cortisol secretory events are lower in FMS patients. During early morning hours, the magnitude and the energy levels of the cortisol secretory events are higher in CFS patients. Due to the lower cortisol clearance rate, there is a higher accumulation of cortisol in FMS patients as compared to their matched healthy subjects. As the FMS patients accumulate higher cortisol residues, internal inhibitory feedback regulates the hormonal secretory events. Therefore, the FMS patients show a lower number, magnitude, and the energy levels of hormonal secretory events. Though CFS patients have the same number of secretory events, the secretion quantity is lower during early morning hours. When we compare the results for CFS patients against FMS patients, we observe different cortisol alteration patterns. In the second part of this thesis, we propose a simplified minimal leptin secretion model and study the correlation between estimated parameters of leptin and cortisol. The hunger hormone leptin and stress hormone cortisol are closely associated with obesity. Traditionally, a leptin-cortisol antagonism is observed in obese patients. We also observe a leptin-cortisol antagonism when we compare the reconstructed leptin and cortisol levels, hence, further validating the model. The proposed model can potentially be employed to study leptin variations in obese patients against their matched healthy subjects. Characterizing CFS, FMS, and obesity based on the hormonal alterations will help us develop effective methods for treating these disorders.
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    https://hdl.handle.net/10657/6702
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